LabMedica International July 2016

V I S I T

W O R L D ’ S C L I N I C A L L A B O R AT O R Y N E W S L E A D E R ISSN 1068-1760

Vol. 33 No. 4 • 6-7/ 2016

DAILY CLINICAL LAB NEWS

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Protein Levels May Help Diagnose Bipolar Disorder series of proteins have been discovered that could be diagnostic markers to identify bipolar I disorder and if this discovery sample can be validated through replication, these markers may help as a diagnostic tool for psychiatrists treating mood disorders.

It is critical to differentiate bipolar disorder from other mood disorders

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new analytical tool for medical applications might be used to diagnose cancer more rapidly than conventional methods and has implications for the field of lipidomics, which involves the identification and quantification of cellular lipid molecules, how they interact with other components in cells and their role in

biological systems.

Scientists at Purdue University (West Lafayette, IN, USA; www. purdue.edu) and their colleagues developed a new approach to easily pinpoint the location of double bonds between carbon atoms in lipid molecules, allowing the identification of “isomers,” a capability that could

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Image: Courtesy of Pacific Biosciences

Tissue Typing Method Revolutionizes Stem Cell Transplantation S aliva and blood samples can be typed using a new system that allows scientists to obtain very high quality information about a patient and donor’s tissue types, enabling them to make the best possible matches.

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New App Connects Point-of-Care Coordinators via Tablet or Smartphone

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new mobile application has been released that allows point-of-care coordinators (POCCs) and laboratory supervisors to control operations from any location.

Modern-day laboratories face modern-day challenges. It is a constant quest to achieve the balance between quality of results and services, speed of

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espite a 60% decline in malaria deaths since 2000, because of better prevention and increased control measures, malaria is still one of the top three killers of children worldwide claiming one life every minute of every day.

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low-cost, easy-to-use urine test to diagnose tuberculosis (TB) among patients with human immunodeficiency virus (HIV) could help reduce the TB death rate of HIV-positive patients in hospital.

HIV-associated tuberculosis is difficult to diagnose and results in high mortality and frequent extra-pulmonary presentation, inability to obtain sputum, and paucibacillary samples limits the usefulness of nucleic-acid

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new blood test has been developed to detect tumor-specific methylated DNA biomarkers that may leak from active lesions into the circulatory system. Current data suggest that a genomic test specific for these biomarkers is more sensitive than carcinoembryonic antigen (CEA) testing and is highly specific.

One element of the standard of care for post-surgical monitoring for CRC (colorectal cancer) recurrence is

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Rapid Low-Cost Urine Test Diagnoses Tuberculosis

Novel Malaria Test Sets New Gold Standard

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Image: The Single Molecule, Real-Time (SMRT) DNA sequencing technology

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Early Test for Colorectal Cancer Recurrence

Lipidomics Technique Offers Faster Cancer Diagnosis

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result delivery and cost-effectiveness of operations. A critical aspect in laboratory operations is the proper management of information technology – the flow of patients’ clinical data and information.

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Clinical News . . . . . . . . . 4-60 IFCC News . . . . . . . . . . . . . 61 EFLM Corner . . . . . . . . . . . 66 Product News . . . . . . . 20-52 Industry News . . . . . . . . . .69 International Calendar . . . 69 PUBLISHED IN COOPERATION WITH

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Tissue Typing Method Revolutionizes Stem Cell Transplantation aliva and blood samples can be typed using a new system that allows scientists to obtain very high quality information about a patient and donor’s tissue types, enabling them to make the best possible matches.

As well as improving outcomes, the technology should be faster than previous techniques, allowing the potential for more donors to be typed every year. Typing more donors would increase the chance of every patient finding a well matched donor – a vital move as currently only 60% of transplant patients receive the best possible match.

The technology, known as Third Generation Sequencing, also allows scientists working for the Anthony Nolan charity (London, UK; www.anthonynolan.org) a further understanding of donor-patient compatibility in stem cell transplantation. The new highly accurate reads of the patient and donor’s human leukocyte antigen (HLA) types will allow the investigators to identify currently unknown factors which contribute to the success or failure of a stem cell transplant. This information could prove to be invaluable for improving the success of future transplants.

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The latest technology resolves this by generating exceptionally long DNA read lengths and by sequencing different tissues types in isolation. The Anthony Nolan scientists are working with new Single Molecule Real-Time (SMRT) DNA sequencing technology (Pacific Biosciences; Menlo Park, CA, USA; www.pacb.com). SMRT Sequencing is built upon two key innovations: zeromode waveguides (ZMWs) and phospholinked nucleotides. ZMWs allow light to illuminate only the bottom of a well in which a DNA polymerase/template complex is immobilized. Phospholinked nucleotides allow observation of the immobilized complex as the DNA polymerase produces a completely natural DNA strand.

Katy Latham, PhD, Director of Laboratories at Anthony Nolan, said, “The implications of this technology could be enormous, allowing for accurate HLA typing in a single experiment and making redundant the need for multiple experiments and cross-referencing of results. This is significant as high resolution HLA typing has been shown to significantly improve outcomes when stem cells transplant recipients and their unrelated donors are matched very closely.”

Novel Malaria Test Sets New Gold Standard cont’d from cover

Malaria is no longer only a disease of sub-Saharan Africa and Southern Asia. Increasing numbers of people emigrating from countries where malaria is endemic have resulted in a higher incidence in Europe and the Middle East. The proportion of imported malaria cases has increased during the last few years from 14% to 86% in more recent studies. The diagnosis of malaria in most developing countries has relied on parasites being identified by examining under the microscope a drop of the patient’s blood, spread out as a “blood smear” on a microscope slide by a specialist. The introduction of rapid diagnostic tests (RDTs) has the potential to significantly improve management of malaria infections, especially in remote areas with limited access to good quality microscopy services, but their sensitivity has been questioned.

The recently CE Marked, illumigene Malaria (Meridian Bioscience; Cincinnati, OH, USA; www.meridian bioscience.com) is a novel, highly accurate test that targets a region of the Plasmodium genome that is conserved across P. falciparum, P. vivax, P. ovale, P. malariV

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ae, and P. knowlesi. Results from illumigene Malaria assays are intended to be used as an aid in the diagnosis of human malaria infection. The test does not require specialized laboratory equipment. The test demonstrated 100% sensitivity, but more importantly, it also detected infected patients that were missed by conventional methods for the identification of malaria. The illumigene Malaria, is a novel, highly accurate test developed by Meridian with the technical assistance of the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA; www.cdc.gov) and Cheikh Anta Diop University (Dakar, Senegal; www.ucad.sn).

The test is up to 80,000 times more sensitive at detecting the malaria parasite than conventional tests, potentially revolutionizing malaria diagnosis and establishing a new gold standard. Using innovative molecular loop-mediated isothermal amplification (LAMP) technology, illumigene results are available in less than one hour, and the test is easy to use as it does not rely on high-level technical expertise. This is a major step forward for people with malaria, as faster and more accurate diagnoses should lead to prompt treatment and better outcomes. The illumigene Malaria DNA amplification assay is performed on the illumipro-10, for the direct detection of Plasmodium spp. DNA in human venous EDTA whole blood specimens from individuals with signs and symptoms of malarial infection.

The illumigene Malaria molecular test uses LAMP technology to amplify DNA and detect the presence of the malaria parasite. LAMP technology is isothermal, therefore can be used at room temperature without the need to heat reagents or the material being tested, unlike some rapid diagnostic tests currently used in malaria which use polymerase chain reaction (PCR) technology and illumigene Malaria does not require refrigeration. illumigene Malaria will be distributed in the European, Middle Eastern and African regions by Meridian Bioscience Europe (Milan, Italy; www.meridian bioscience.eu) and in additional international markets by the Company’s global distribution network.

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ISSN 1068-1760 Vol.33 No.4. Published, under license, by Globetech Media LLC; Copyright © 2016. All rights reserved. Reproduction in any form is forbidden without express permission. Opinions expressed are solely those of the authors, and do not represent an endorsement, or lack thereof, by the Publisher of any products or services.

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Rapid Low-Cost Urine Test Diagnoses Tuberculosis cont’d from cover

amplification tests and smear microscopy. A team of international scientists led by those at the University of Cape Town (South Africa; www.uct.ac.za) randomly allocated 2,528 patients with HIV from 10 hospitals in four countries in sub-Saharan Africa (four in South Africa, two in Tanzania, two in Zambia, and two in Zimbabwe) to receive either routine testing including smear, Xpert MTP/RIF (Cepheid, Sunnyvale, CA, USA; www.cepheid.com) and culture, as well as the LAM urine-test (LAM group, 1,257 patients) or routine testing alone (no-LAM group, 1,271 patients).

All patients were asked to provide a urine sample of at least 30 mL at enrolment, and trained research nurses did the LAM test in patients allocated to this group using the Alere Determine tuberculosis LAM Ag lateral flow strip test (Alere; Waltham, MA, USA: www.alere.com) at the bedside on enrolment. The LAM urine-test detects a glycolipid molecule (lipoarabinomannan), which is linked to TB. It provides a result in 25 minutes and each test costs about USD 2.66.

Eight weeks after being discharged from hospital, 21% (261)

of patients in the LAM group had died compared to 25% (317) of patients in the non-LAM group, an absolute reduction of 4%.

A greater proportion of patients in the LAM group (648; 52%) were treated for TB than in the no-LAM group (598; 47%).

Those who started TB treatment, a higher proportion of patients were treated in the first three days in the LAM group (513/648; 79%) compared to the non-LAM group (413/598; 69%).

The effect of LAM testing on mortality varied by country but the highest sensitivity was found in people with the lowest CD4 cell count, a measure of how badly the immune system is damaged in patients with HIV, who are the hardest to diagnose with TB using routine testing. The authors found that the LAM urinetest had a sensitivity of 46% (the proportion of people with TB correctly diagnosed) and specificity of 90% (the proportion of healthy people who are correctly identified as healthy). The study was published on March 9, 2016, in the journal the Lancet.

Image: The Determine tuberculosis LAM Ag lateral flow strip test (Photo courtesy of Alere).

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Lipidomics Technique Offers Faster Cancer Diagnosis cont’d from cover

lead to the early diagnosis of cancer. Lipids are important components of living cells and include fats, oils and waxes. They may exist as isomers, which have identical mass but possess subtle structural differences not easily detected by conventional analytical technologies. The new tool uses techniques called tandem mass spectrometry and the Paternò-Büchi reaction.

In tandem mass spectrometry, charged molecules are fragmented into pieces, which are then measured and identified by their mass. A so-called “shotgun lipidomics” analysis enhanced by the Paternò-Büchi photochemical reaction, which modifies double bonds into rings that can then be easily cleaved into two parts. This allows the bonds to be measured and identified using mass spectrometry.

Although the study was conducted using a conventional laboratory mass spectrometer, the same operation could be carried out with a new miniature mass spectrometer. Whereas conventional mass spectrometers are relatively heavy, bulky instruments, Purdue scientists have recently developed miniature mass spectrometers, including the Mini 12, (PURSPEC Technologies Inc.; West Lafayette, IN, USA; www.purspec.us) which weighs 18 kg, is 31.8 cm wide and 40.6 cm high.

Zheng Ouyang, PhD, a professor and coauthor of the study, said, “Direct analysis using ambient sampling methods will further speed up the analysis process from hours to a minute. We want to apply this to imaging to study tissue, and we currently are integrating this method into miniature mass spectrometry systems. Eventually we hope to have biologists and medical professionals using it.” The study was published on February 22, 2016, in the journal Proceedings of the National Academy of Sciences of the United States of America).

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Early Test for Colorectal Cancer Recurrence cont’d from cover

quarterly or semi-annual blood-based testing to measure CEA levels, which has poor sensitivity and specificity. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide, accounting for more than 600,000 deaths each year. When diagnosed early, before cancer has spread, the relative five-year survival rate for CRC is 90%, but only about 4 out of 10 CRC cases are detected early.

Among individuals undergoing surgical treatment for CRC, recurrence occurs in 30% to 40% of all cases, the majority of which present in the first two to three years following initial diagnosis and treatment. This early and concentrated pattern is relatively unusual among cancers, and offers the opportunity for structured surveillance to detect signs of recurrence.

Clinical Genomics (Edison, NJ, USA; www.clinicalgenomics.com) has announced new data supporting its 2-gene blood test for post-surgical monitoring of colorectal cancer recurrence. In one study investigators compared the sensitivity and specificity of methylated Branched Chain Amino-Acid Transaminase 1 (BCAT1) and IKAROS Family Zinc Finger 1 (IKZF) (2-gene test) with those of CEA in blood to monitor patients for recurrence of colorectal cancer following potentially curative resection of a primary tumor. Recurrence was assessed by clinical findings and periodic computed tomographic surveillance scans.

The presence in blood of either methylated BCAT1 or IKZF1 or elevated CEA was considered positive for recurrence.

Interim study results reflect data from 120 patients with known recurrence status (30 recurrences confirmed via imaging or other clinical means; 90 patients with no evidence of recurrent CRC).

Overall sensitivity estimates for recurrence were 63% (19/30) for methylated BCAT1/IKZF1 versus 23% (7/30) for CEA. Specificity estimates in the 90 patients with no evidence of disease were 86% for methylated BCAT1/IKZF1 versus 96% for CEA. No cases with confirmed recurrence were CEA positive only.

The authors of the studied concluded that their results demonstrate that BCAT1 and IKZF1 are highly methylated in colorectal cancer tissue with low methylation levels in surrounding non-tumor tissue, suggesting that these methylated genes are highly tumor-specific without a VISIT US AT: field effect. The presence of methylated BCAT1 and IKZF1 in blood appears to be related to tumor invasiveness, enabling 2016 ANNUAL tumor access to the bloodstream. The MEETING studies were presented on January 23, Booth: 4012 2016, at the American Society of Clinical Oncology 2016 Gastrointestinal Cancers Symposium (ASCO GI) held in San Francisco (CA, USA; http://gicasym.org).

Image: Colon cancer cells (Photo courtesy of LifeExtension).

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Expanded Genetic Test For Breast Cancer ext-generation sequencing (NGS) allows testing for mutations in additional breast cancer predisposition genes. The frequency of germline mutations detected by using NGS has been reported in patients with breast cancer who were referred for Breast Cancer Early Onset 1 and 2 (BRCA1/2) testing or with triple-negative breast cancer.

The frequency and predictors of mutations in 25 cancer predisposition genes, including BRCA1/2, has been assessed in a sequential series of patients with breast cancer at an academic institution to examine the utili-

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ty of genetic testing in this population.

A team of scientists led by those at Beth Israel Deaconess Medical Center (Boston, MA, USA; www. bidmc.org) evaluated 488 patients newly diagnosed with breast cancer for mutations in 25 cancer genes at the Dana-Farber Cancer Institute (Boston, MA, USA; www.dana-farber. org). Personal and family cancer histories were collected and germline DNA was sequenced with NGS to identify mutations.

The team used the Myriad myRisk Hereditary Cancer test (Myriad Genetic Laboratories; Salt Lake City, UT,

USA; www.myriad.com). The results show that 52 patients, or 10%, had a germline mutation in a breast cancer predisposition gene, including 6.1% in BRCA1/2 (5.1% in nonAshkenazi Jewish patients).

Approximately 30 mutations were in BRCA1/2 genes and 21 were in other cancer genes, representing a 70% increase in mutations identified above BRCA testing alone.

Importantly, of the women with deleterious mutations 22, or 42%, were diagnosed after age 45, suggesting that older patients may benefit from genetic testing using the 25gene panel.

Anne-Renee Hartman, MD, senior vice president of clinical development at Myriad Genetic Laboratories and a co-author of the study said, “This is the first study to show the frequency of germline mutations in BRCA1/2 and other breast cancer predisposition genes in a sequential series of breast cancer patients prospectively collected and unselected for family history or age. Overall, the 25gene panel identified 70% more

breast cancer causing mutations than BRCA1/2 testing alone. This important new finding is being used to identify more patients with mutations with the ultimate goal of helping them and their families to take appropriate risk reduction measures.” The study was published on March 14, 2016, in the Journal of Clinical Oncology.

Image: The myRisk hereditary cancer screening collection kit (Photo courtesy of Myriad Genetic Laboratories).

New App Connects Point-of-Care Coordinators via Tablet or Smartphone cont’d from cover

Roche (Basel, Switzerland; www.roche.com) developed the cobas infinity Point-ofCare mobile application. This app is available for iOS and Android devices and works on smartphones and tablets in conjunction with the Roche cobas IT 1000 program.

The app provides interoperability across the full Roche POC portfolio including AccuChek Inform II, CoaguChek XS Plus and Pro, cobas h 232, cobas b 101, Urisys 1100, cobas b 121, cobas b 123, and cobas b 221 for diverse clinical disciplines, such as clinical chemistry, immunology, hematology, coagulation and urinalysis.

“From the outset, the app was designed with the POCC in mind,” said Georgios Spitadakis, lifecycle leader for workflow and IT at Roche.

“The cobas infinity POC mobile is not just PC software on a smaller screen or with a different design. It has been designed by POCCs for POCCs to help them carry out their LINKXPRESS COM

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most essential routine tasks efficiently and easily with a mobile device.”

Image: A screenshot from the cobas infinity POC mobile application (Photo courtesy of Roche).

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Multigene Test Identifies Early Breast Cancer he 21-gene Recurrence Score (RS) assay, nodal status, grade, and immunohistochemical markers are recommended for chemotherapy decision-making in hormone receptor positive/human epidermal growth factor receptor negative (HR+/HER2–) early breast cancer (EBC).

HR+ means the breast cancer is hormone receptor positive, indicating the cancer cells have high numbers of receptors for estrogen (ER) or progesterone (PR) on their surfaces, allowing the hormones to drive cancer growth. HER2 negative (HER2−) means the breast cancer cells do not have high numbers of epidermal growth factor receptors and so will not respond to treatment with trastuzumab (Herceptin) and other therapies that target HER2.

Scientists at the West German Study Group, Clinical Research (Mönchengladbach, Germany; www.wsg-online.com) prospectively used RS to define a low-risk subset of patients with node negative disease with high-risk traditional parameters VISIT US AT: and patients with node positive disease (HR+, HER2−) who could be treated with adjuvant endocrine therapy alone. From 2016 2009 to 2011, they enrolled 3,198 paANNUAL MEETING tients; median age of 56 years; 41.1% had Booth: 301 node-positive and 32.5% grade 3 disease.

The 21-gene RS test analyzes 21 genes that can influence the development of cancer and how it responds to treatment.

The test result is a number from 0–100.

The patients were classed as either medium or high risk (RS score over 25) and were randomized to receive one of two types of chemotherapy: six cycles of docetaxel/cyclophosphamide or four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel. After a median follow-up of 55 months, the investigators found that 94% of patients in the hormonal-therapy only group (the ones whose gene test predicted they had a low risk of recurrence), were still alive and disease-free five years after diagnosis. Of the higher risk patients who received chemotherapy as well as hormonal therapy, those classed as medium-risk patients also showed a 94% disease-free survival five years after diagnosis, while for the highrisk patients, this figure was 84%.

Oleg Gluz, MD, one of the study coordinators, said, “In this prospective trial for patients who had a clinically-determined intermediate or high risk of recurrence and who had 0–3 lymph nodes involved, we have been able to identify about 15% who were assessed by the 21gene RS as being at low genomic risk. We were thus able to treat them by anti-hormonal therapy alone and to spare them chemotherapy. The 94% disease-free survival rate that we observe after five years without adjuvant chemotherapy is an excellent result.” The study was presented at the 10th European Breast Cancer Conference (EBCC-10) held March 9-11, 2016, in Amsterdam (The Netherlands; www.ecco-org.eu).

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Image: A breast cancer cell (Photo courtesy of the CDC).

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Paper-Based DNA Amplification Test to Simplify Infectious Disease Diagnostics simple and rapid paper-based diagnostic platform for diseases caused by pathogenic microorganisms was described in a recent paper. Investigators at McMaster University (Hamilton, Canada; www.mcmaster.ca) have incorporated the reagents required for rolling circle DNA amplification (RCA) into a paper-pullulan matrix. Pullulan is an edible, mostly tasteless polysaccharide polymer consisting of maltotriose units. The chief commercial use of pullulan is in the manufacture of edible films that are used in various breath freshener or oral hygiene products.

Rolling circle replication is a process of unidirectional nucleic acid replication that can rapidly synthesize multiple copies of circular molecules of DNA or RNA, such as plasmids, the genomes of bacteriophages, and the circular RNA genome of some viruses.

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The RCA technique, which can produce massive DNA amplicons that can be easily visualized, was found to be more efficient in the paper matrix than in solution, which the investigators attributed to a significantly higher localized concentration of immobilized DNA. The investigators developed a fully functional paper device for sensitive DNA or microRNA detection via printing of all RCA-enabling molecules within a polymeric sugar film formed from pullulan, which was integrated with the paper device. This encapsulation not only stabilized the entrapped reagents at room temperature but also enabled colorimetric bioassays with minimal steps.

“The new test involves printing of all required components needed to amplify a DNA or RNA target directly on paper,” said contributing author Dr.

John Brennan, professor of chemistry at McMaster University. “The user only needs to add the sample to the paper and wait a few minutes for a color to develop.”

The RCA paper test was described in the January 8, 2016, online edition of the journal Angewandte Chemie.

Image: The targets on the paper test (L) change color to indicate infection (Photo courtesy of Matt Terry, McMaster University).

Improved Microscopy May Identify Best Viable Sperm Cells for Reproductive Assistance esearchers’ cutting-edge, stain-free innovation enables more effective screening for and identification of high-quality sperm candidates for assisted reproductive technology (ART).

Physical, emotional, and financial toll of ART treatments is high because success rates of are still low (20%–30%), so ART is often the last resort for reproductively challenged couples or individuals. A team of scientists, led by Dr. Natan Shaked, PhD, at Tel Aviv University (TAU; Tel Aviv, Israel; https:// english.tau.ac.il) and his MSc student, Dr. Miki Haifler, MD, has devised a new method using interferometric phase microscopy (IPM) that allows analysis without staining, which can affect viability, so sperm cannot be stained if fertilization is the goal as it may result in damaged fetuses. Sperm are nearly

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transparent under standard microscopy methods; their optical properties differ only slightly from surroundings, resulting in weak image contrast. The challenge is to pinpoint strong sperm candidates without staining, while still being able to characterize viability.

In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are two effective ART methods available today. The new method is applicable to both, and is especially helpful in ICSI. “Until now, clinicians have chosen the ‘best’ sperm according to their speed, but speed is not necessarily an indicator of DNA quality,” said Dr. Shaked, “Some of the best sperm candidates are slow or even immobile because their tails have malfunctioned. If we can better determine the full structure

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and composition of the sperm, the success rate of ART treatments will be higher, leading to more births without congenital defects. In cases where sample staining is impossible – such as IVF and ICSI – our device provides a promising new direction.”

The new device is a small box that attaches to an existing, even conventional microscope. It is smaller, cost-effective (about USD 1,000), and easier to align than conventional interferometric imaging methods. It is joined to new automated software that produces a thickness map of the sample and other physical parameters to evaluate sperm viability – in real time. The new imaging process, which harnesses phase imaging methods to record passage of light through a sample to assess thickness, can quantify quality of sperm used in ART, leading to more successful treatments.

In the study, to help evaluate the potential of IPM for clinical sperm analysis without staining, the researchers compared label-free IPM to labelfree and label-based bright-field microscopy (BFM) in evaluating sperm cell morphology according to World Health Organization (WHO) criteria. Sperm cells from healthy donors were obtained from the male fertility clinic at Chaim Sheba Medical Center (Tel Aviv, Israel). Parameters evaluated were: length and width of the sperm head and midpiece; size and width of the acrosome; head, midpiece, and tail configuration; and general normality of the cell. Results showed that label-free IPM can identify sperm cell abnormalities with excellent correlation compared with label-based BFM, and with higher accuracy compared with label-free BFM. To enable IPM as part of clinical sperm selection procedures, the team is preparing to begin clinical trials on IVF patients in Israel.

The study, by Haifler M, Girshovitz P, et al., was published July 2015, in the journal Fertility and Sterility.

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Simple Test for Kidney Function Needs More Consideration idney disease in the USA and other parts of the world is both common and under-diagnosed, but new studies suggest that paying close attention to results of a simple blood test can help predict the likelihood that patients will develop kidney failure.

A single determination of estimated glomerular filtration rate (eGFR) associates with subsequent mortality risk and prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. The eGFR is usually based on serum creatinine level, age, sex, and race. The most widely used method for this is the abbreviated MDRD equation, as it has proved the most robust and accurate.

A large team of scientists led by those at Johns Hopkins Bloomberg School of Public Health (Baltimore, MD, USA; www.jhmi.edu) analyzed data on more than 1.2 million subjects with and without kidney disease, more than 102,000 of whom died over a three-year study period. They primarily focused on the results of tests of the eGFR, which is used to screen for and detect early kidney damage and to monitor kidney function. They looked at the most recent eGFR but also at test results over time in the same patients.

The investigators found that the most recent eGFR value was the most valuable when it came to predicting both kidney failure and mortality, looking at historical tests also provided information that could be useful to patients and physicians. Electronic medical records routinely found in many hospitals and physicians’ offices should be useful in determining the trajectory of kidney function over time. Having this information not only informs prognosis, but can help doctors steer their patients toward treatments such as ACE inhibitors which can slow the decline in kidney function among patients with protein in their urine or away from non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen which can damage the kidneys.

Josef Coresh, MD, a Professor of Epidemiology and coauthor of the study said, “Patients and physicians should pay attention to the estimates of kidney function which are routinely obtained, but all-too-often ignored. It costs little to do this test and it is done all the time. The results can inform treatment decisions that may be able to slow kidney function decline. While the test is more informative to doctors than a glucose test for diabetes, the results are many times overlooked, particularly when a patient has other chronic illnesses that required more immediate consideration.” The study was published on December 11, 2015, in the Journal of the American Society of Nephrology.

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Image: The glomerular filtration rate (GFR) calculator used to estimate chronic kidney disease (Photo courtesy of The National Institute of Diabetes and Digestive and Kidney Diseases).

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3D Printed Diagnostic Device Rapidly Detects Anemia new biomedical device has been developed using 3D printers to create a low cost, point-of-care device that can quickly detect anemia, a condition in which the blood does not have enough healthy red blood cells to transport oxygen to the body’s organs. Point-of-care devices give the user fast, easy-to-understand results from a test performed outside of a laboratory, such as a blood glucose test or pregnancy test and identifying a blood disorder may be as easy as running a blood sample from a finger prick under a smartphone.

Scientists at Kansas State University (Olathe, KS, USA; www.k-state.edu) made the device with a Projet 1200 3D printer (3DSystems; Rock Hill, SC, USA; www.3dsystems.com) and designed it to detect anemia for individuals who have limited access to health care, such as those living in developing countries. Anemia affects two billion people world-

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wide, including more than half of preschool children and pregnant women in developing countries and at least 30% of children and women in some industrialized nations.

The device consists of 3D printed clear plastic slides containing microfluidics that attach to a smartphone. The user adds a drop of their blood to a slide, which is used for a color scale-based test.

The test results are produced in less than 60 seconds and can be read using a smartphone. A companion app is being developed with Steve Warren, PhD, an associate professor in electrical and computer engineering at Kansas State University, which could manage data from the blood sample and even send the results to a doctor.

Kim Plevniak, a master’s student in biological and agricultural engineering, who worked on the device, said, “Anemia is a very prevalent condition

in developing countries even though it is easily treated with iron supplements or vitamins and can be prevented with a healthy diet. Often in these developing countries people will have much easier access to smartphones than they will to doctors and trained medical professionals.”

Image: The Projet 1200 3D printer (Photo courtesy of 3DSystems).

Portable Device Developed for Rapid Highly Sensitive Diagnostics low-cost and portable microfluidic diagnostic device has been developed for remote regions with limited health facilities experiencing an epidemic, which need portable diagnostic equipment that functions outside the hospital.

Over the past several years, microfluidic devices have shown extraordinary potential in the area of diagnostic and most are composed of silicone rubber with minuscule channels the width of a hair. These microfluidic devices can rapidly detect a number of different biomarkers in very small quantities of blood.

Bioengineers at the Ecole Polytechnique Fédérale de Lausanne (Switzerland; www.epfl.ch) have engineered a portable device that runs on battery power and is completely self-sustained. It operates with inexpensive microscopes and provides very high levels of accuracy and detection. The biomarkers are usually enzymes, proteins, hormones or metabolites and the concentration of these molecules in the blood provides precise information on the patient’s health condition. The multiplexed digital-analog microfluidic platform was able to rapidly and with high sensitivity detect three to four biomarkers in quadruplicate in 16 independent and isolated microfluidic unit cells requiring only a single 5 L sample.

The scientists comprehensively characterized the platform by performing single enzyme and digital immunoassays, achieving single molecule detection. Initial testing has been successfully carried out on a sample containing anti-Ebola antibod-

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ies, which indicate the presence of the virus in both symptomatic and asymptomatic patients. The team detected anti-Ebola immunoglobulin G (IgG) in ultralow volume whole blood samples to levels of 100 pM in a multiplexed assay format. The device could potentially work with a large number of other protein biomarkers and molecules.

The device is unique in that it is composed of both analog and digital detection mechanisms, while conventional devices hitherto only integrated one or the other. Digital detection is highly sensitive and can detect the presence of a single biomarker. However, it is less effective when the concentration of biomarkers is too high, due to signal saturation. Analog measurements, on the other hand, function best at higher biomarker concentrations. Using these two detection mechanisms simultaneously, the composition of a drop of blood can be thoroughly analyzed in a short amount of time. The analysis provides precious medical information: it could help doctors make an early diagnosis or determine the stage of a disease.

Francesco Piraino, PhD, the lead author of the study, said, “The platform will lead the development of new kinds of tests to meet the increasing demand for on-site diagnostic testing. It will prove very useful for medical staff working in resourcelimited regions. The device could, for example, be used to monitor endemic, epidemic, and pandemic disease outbreaks.” The study was published on January 12, 2016, in the journal ACS Nano.

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Antibody Levels in Saliva Linked to Risk of Mortality mmunoglobulins (Ig) or antibodies are proteins secreted by white blood cells (B lymphocytes), which circulate in the body and tag, destroy, and/or neutralize bacteria, viruses, and other harmful or foreign materials, the antigens.

Secretory IgA (sIgA) is secreted at the mucosal surfaces such as the mouth, nose, gastrointestinal tract, and can be measured in saliva.

SIgA is the first line of defense against infection at these surfaces, acting to prevent colonization by microbes. It is considered particularly key in the defense against viral and bacterial infections of the upper respiratory tract (URTIs), such as colds and influenza.

Scientists at the University of Birmingham (Edgbaston, UK; www.birmingham.ac.uk) and their colleagues collected saliva and data derived from the oldest of three age cohorts in the West of Scotland.

Of the 1,042 participants who took part in the first wave of the study, 723 were re-interviewed at the third wave, the baseline for the analysis; 91 participants died before wave three leaving 951 participants eligible for participation. Participants were interviewed in their own homes by nurses who were trained in a standardized manner in how to administer a standardized interview schedule and collect the saliva sample.

Saliva samples were taken at the end of the interview but before taking any other physical measures using a standard salivette (Sarstedt Ltd., Leicester, UK; www.sarstedt.com). All samples were frozen within two hours of collection and remained frozen at -20 °C until assay. Samples were recovered after thawing by centrifugation at 1,000 g for 10 minutes. Secretory IgA concentration was measured by double antibody sandwich enzymelinked immunosorbent assay (ELISA). The 639 participants’ saliva was sampled in 1995 when they were aged 63 years. Their IgA secretion rate was measured and the mortality rate was tracked over the following 19 years.

The team found that there was a negative association between log sIgA secretion rate and allcause mortality. Further analysis of specific causes of mortality revealed that the all-cause association was due to an underlying association with cancer mortality and in particular with cancers other than lung cancer. The hazard-ratio (HR) for non-lung cancer was 0.68 implying a 32% reduction in mortality risk per standard deviation rise in log sIgA secretion rate. Higher secretion rates of sIgA were associated with a decreased risk of death from cancer, specifically non-lung cancer, as well as from respiratory disease. Thus, it appears that sIgA plays a protective role among older adults, and could serve as a marker of mortality risk, specifically cancer mortality.

Anna C. Phillips, PhD, the lead author of the study, said, “There are a number of factors that can affect how well we produce antibodies and maintain their levels. It is not yet known how saliva samples could be used in checkups, as scientists have yet to establish what secretion rate would be considered the threshold level before becoming a cause of concern, otherwise known as the “protective level. If the level is very low, this could be considered a useful early indicator of risk.” The study was published on December 23, 2015, in the journal Public Library of Science ONE.

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Image: The Salivette collection device for saliva samples (Photo courtesy of Sarstedt).

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Molecular Studies of Suppressor Gene Advance Understanding of Metastasis gene that is known to suppress the growth and spread of many types of cancer has the opposite effect in some forms of colorectal cancer and these findings may lay the foundation for new colorectal cancer treatments.

Cancer deaths attributed to colorectal cancer are mainly due to tumor recurrence and metastasis to other organs and excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the USA. It is estimated that the lifetime risk of developing colorectal cancer is about 1 in 20.

Scientists at the University of Missouri (Columbia, MO, USA; www.missouri.edu) used cancer cell models, mouse models and human biopsy samples and by using different molecular methods, the team found that the Sprouty2 (SPRY2) gene functions differently in colorectal cancer (CRC) than in other types of cancers. Sprouty (SPRY) is an intracellular regulator of receptor tyrosine kinase signaling involved in growth, differentiation and tumorigenesis. Four family members of SPRY (SPRY1–4) have been identified. SPRY2 appears to be ubiquitously expressed, whereas other family members show organ and tissue specificity.

Among the various techniques used, 3 UTR reporter assays were performed and the luminescence was measured by a luminometer (Turner

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Biosystems Inc.; Sunnyvale, CA, USA; www. turnerbiosystems.com) confocal microscopy using a Leica TCS SP8 confocal laser scanning microscope (Leica Microsystems Inc.; Buffalo Grove, IL, USA; www.leica-microsystems.com) was performed; and formalin-fixed, paraffin-embedded human colorectal cancer (CRC) tissue microarray (Biomax; Rockville, MD, USA; www.biomax.us) was utilized for V-Akt Murine Thymoma Viral Oncogene Homolog 2(AKT2) and E-cadherin (CDH1) immunostaining.

The team found that in colorectal cancer, SPRY2 may increase the metastatic ability of cancer cells instead of suppress it. SPRY1 and SPRY2 messenger ribonucleic acid (mRNA) transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and epithelial-mesenchymal transition inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. By confocal microscopy, they demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194.

Sharad Khare, PhD, an associate professor and senior author of the study said, “The gene known as Sprouty2 has previously been shown to protect

against metastasis, or the spreading of cancer to other parts of the body, in breast, prostate and liver cancer. However, our recent molecular studies found that this gene may actually help promote metastasis instead of suppress it. This finding is a very significant step in our understanding of metastasis in colorectal cancer, but it’s important to note that we believe this phenomenon may occur in only a subset of colorectal cancer patients.” The study was published originally in advance of print, online on October 5, 2015, in the journal Oncogene.

Image: The TCS SP8 confocal laser scanning microscope (Photo courtesy of Leica Microsystems).

Fungal Infection Identified by Pathogen Detection Array Technology atients who are undergoing treatment for diseases such as cancer often face the added challenge of a compromised immune system, which can be challenging to both of their condition and the drugs used to treat it, leaving them vulnerable to various opportunistic infections.

A novel investigational technology has been developed that can rapidly identify elusive microorganisms which are not only life-threatening, but those caused by rare organisms are extremely difficult to isolate and identify.

Scientists at the University of Pennsylvania (Philadelphia, PA, USA; www.uphs.upenn.edu) utilized a pathogen array technology referred to as PathoChip, comprised of oligonucleotide probes that can detect all the sequenced viruses as well as known pathogenic bacteria, fungi and parasites and family-specific conserved probes, thus providing a means for detecting previously uncharacterized members of a family. The technology contains 60,000 probes that simultaneously test for all known viruses, as well as a variety of bacteria, fungi,

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helminths, and protozoa.

The investigators applied the PathoChip test to tissue samples of a patient with relapsed acute myelogenous leukemia (AML). The patient, a middle-aged man, had undergone chemotherapy for the cancer, a treatment that is well known to weaken the immune system, increasing susceptibility to infection. As a result, he developed an unknown fungal infection.

Erle Robertson, PhD, a professor and vice-chair for research in Otorhinolaryngology, said, “We’ve run many tests to see if we could identify pathogens in the laboratory, just to see if the PathoChip has efficacy in identifying a variety of organisms, and we were able to identify all infectious agents tested, but this was the first time we actually looked directly at a patient sample to identify a pathogenic agent. With this technology, out of 60,000 possibilities and probes that we used, in a little over 24 hours we were able to identify this particular fungi.” The study was published originally online on November 20, 2015, in the journal Cancer, Biology & Therapy.

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Oral Bacteria Linked to Risk Of Intracerebral Hemorrhage hysicians have an increased understanding of patients entering the hospital for acute stroke, and the association between certain types of stroke and the presence of the oral bacteria centronuclear myopathies gene (cnm)positive Streptococcus mutans.

Small vessel diseases (SVDs) of the brain such as cerebral microbleeds (CMBs), lacunar infarcts, and white matter lesions are important biomarkers of vascular injury and burden of brain dysfunction. The underlying mechanisms and risk factors of the SVDs of the brain are poorly understood.

A team of scientists led by those at the National Cerebral and Cardiovascular Center (NCVC; Osaka, Japan; www.ncvc.go.jp) enrolled patients admitted to the NCVC because of acute heart disease, between February and August 2014, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with intracerebral hemorrhage (ICH). The cnm gene in S. mutans isolated from sali-

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va was screened using polymerase chain reaction (PCR) techniques and its collagen-binding activities examined. Oral saliva and dental plaque specimens were collected from the subjects in the first three days following admission.

Oral samples were inoculated on Mitis-Salivarius medium with bacitracin (MSB, 100 U/mL; SigmaAldrich; St. Louis, MO, USA; www. sigmaaldrich.com) and 15% sucrose (MSB agar) and anaerobically incubated at 37 °C for 48 hours. S. mutans strains were isolated morphologically and all strains were anaerobically grown in brain heart infusion (BHI) broth (Difco Laboratories; Detroit, MI, USA; www.bd.com) at 37 °C for 24 hours. DNA of each strain was extracted. S. mutans and cnm gene encoding CBP was screened using polymerase chain reaction techniques. MKD primer32 was used to detect S. mutans and cnm primer was used to identify cnm gene33. A collagen-binding assay with type I collagen was conducted to examine collagen-binding activities of each iso-

lated S. mutans strain.

Eleven cases showed Streptococcus mutans strains positive for cnm.

The presence of cnm-positive Streptococcus mutans was significantly associated with ICH and increased number of deep CMBs. In subjects positive for Streptococcus mutans, collagen-binding activity was positively correlated with the number of deep CMBs. The authors hypothesize that the S. mutans bacteria may bind to blood vessels weakened by age and high blood pressure, causing arterial ruptures in the brain, leading to small or large hemorrhages.

Robert P. Friedland, MD, a professor of Neurology and co-author of the

study, said. “This study shows that oral health is important for brain health. People need to take care of their teeth because it is good for their brain and their heart as well as their teeth. The study and related work in our laboratories have shown that oral bacteria are involved in several kinds of stroke, including brain hemorrhages and strokes that lead to dementia.”

The study was published online on February 5, 2016, in the journal Scientific Reports (www.nature.com).

Image: The cnm-negative S. mutans bacteria, found in approximately 10 percent of the general population (Photo courtesy of National Cerebral and Cardiovascular Center).

Novel Saliva Test Identifies and Tracks Cancer rapid, accurate test that can detect biomarkers of lung cancer in saliva is soon to be trialed in patients and the test takes only 10 minutes to give a result and could be done in the doctor’s office.

A method called “liquid biopsy” that detects circulating tumor DNA in bodily fluids such as saliva and blood and the liquid biopsy holds the promise of rapid, less invasive identification of cancers and easier tracking of disease progress during treatment.

Scientists at the University of California-Los Angeles (UCLA; CA, USA; www.ucla.edu) developed the device that uses electric field-induced release and measurement (EFIRM) to detect non-small-cell lung cancer (NSCLC) biomarkers in saliva. The EFIRM device analyzes the contents of exosomes, which are tiny bags of molecules that cells release now and again. The device forces the exosomes to release their contents and carries out bio-recognition of the released biomolecules at the same time, and the method is high accurate compared with current sequencing technology.

The test works by detecting genetic mutations in a protein called epi-

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dermal growth factor receptor (EGFR). The protein normally helps cells grow and divide, but some NSCLC cells have too much EGFR, which makes them grow faster.

Drugs called EGFR inhibitors that block the protein could be ordered promptly by a clinician. The key finding came from a blind and randomized clinical study that used saliva samples procured from lung cancer patients. Using the EFIRM method to detect two key tumor-causing mutations in the EGFR gene (L858R and exon 19 deletion) in saliva, the investigators achieved nearly identical results as with bronchoscopy-based detection of the same two mutations.

David T.W. Wong, DMD, DMSc, Director for UCLA Center for Oral/ Head & Neck Oncology Research, who led the study, sees the test forming part of a set of diagnostic tools. For example, should a lung X-ray show a suspicious nodule, and then the doctor could use the saliva test to rapidly find out if cancer is likely. The study was presented at the 2016 Annual Meeting of the American Association for the Advancement of Science that was held February 11–15, 2016, in Washington DC (USA).

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2D Gel Immunoblot Test Detects Mesothelioma Biomarkers in the Blood Years Prior to Symptoms n advanced two-dimensional gel electrophoresis test has demonstrated the presence of a biomarker for mesothelioma in the serum of individuals four to 10 years before the appearance of clinical symptoms.

Malignant mesothelioma is a rare form of cancer that develops from transformed cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is usually caused by exposure to asbestos. The most common anatomical site for the development of mesothelioma is the pleura (the outer lining of the lungs and internal chest wall), but it can also arise in the peritoneum (the lining of the abdominal cavity), the pericardium (the sac that surrounds the heart), or the tunica vaginalis (a sac that surrounds the testis). The three-year survival rate for patients with this disease is only 8%, as most patients are diagnosed with late stage disease with limited therapeutic options.

Investigators at the biomedical company MorNuCo Inc. (West Lafayette, IN, USA; http:// mornuco.com) used their proprietary ONCOblot cancer detection test to determine the serum presence of mesothelioma-specific protein transcript variants of ecto-nicotinamide adenine dinucleotide oxidase disulfide-thiol exchanger 2 (ENOX2), a re-

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cently identified marker of malignancy. ENOX proteins are expressed on the cell surface of malignancies and are detectable in the serum of patients with cancer.

In the ONCOblot procedure, ENOX2 proteins are separated from the bulk of the albumin and other serum proteins by two-dimensional separation with separation in the first dimension by isoelectric focusing and separation in the second dimension by sodium dodecyl polyacrylamide gel electrophoresis.

After transfer of proteins from gels to a nitrocellulose membrane, the detection step utilizes a proprietary recombinant pan-ENOX2 antibody that crossreacts with all known ENOX2 isoforms of human origin. Presence of any ENOX2 proteins is recognized as dark spots on a light background. The test results reveal a pattern of ENOX2 proteins in a patient’s sera. This serves not only as a molecular indicator of cancer presence but precisely identifies the tissue of origin of the cancer.

In the current study, sequential serum samples collected from asbestos-exposed individuals prior to the development of frank mesothelioma were assayed for ENOX2 presence by two-dimensional gel immunoblot analysis to determine how long in advance of clinical symptoms mesothelioma-specific ENOX2 transcript variants could be detected.

Results revealed that two mesothelioma-specific ENOX2 protein transcript variants were detected in the serum of asbestos-exposed individuals four to 10 years prior to clinical diagnosis of malignant mesothelioma (average 6.2 years). Either one or both ENOX2 protein transcript variants indicative of malignant mesothelioma were absent in 14 of 15 subjects diagnosed with benign pleural plaques either with or without accompanying asbestosis.

The ONCOblot study was published in the January 22, 2016, online edition of the journal Clinical Proteomics.

Image: The ONCOblot two-dimensional gel electrophoresis/western blot test is already making a difference in the lives of patients (Photo courtesy of MorNuCo).

New Approach to Aid in Diagnosing Lower Back Pain n a clinical study, scientists have identified a potential new method, based on biochemical profiling of serum for circulating cytokines, that may assist in refining personalized diagnoses of disc diseases and possibly even in distinguishing between severe and mild conditions.

Physicians trying to diagnose lowback pain (LBP) look at many potential causes and unpredictable responses to treatment as LBP can come from any of various causes that can present in similar ways. In a new study, scientists from Feinstein Institute for Medical Research (Manhasset, NY, USA; www.feinstein institute.org) in collaboration with clinicians from Northwell Health (Manhasset, NY, USA; www. northwell.edu) performed multiplex assays on blood serum samples from 133 participants to examine biochemical profiles of cytokines (and matrix metalloproteinases).

The team, led by Nadeen Chahine, PhD, associate investigator, Feinstein Institute, recruited participants from Northwell Health: from a spine neurosurgery practice

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(n = 80), a back pain management practice (n = 27), or a control cohort (n = 26). Participants with LBP had been diagnosed with intervertebral disc herniation (IDH), spinal stenosis (SS), or degenerative disc disease (DDD), but had not yet begun treatment. The main findings were that serum levels of the proinflammatory cytokine interleukin-6 (IL-6) were significantly higher in subjects with LBP compared with control participants, and that participants with SS or DDD had higher levels than those with IDH and controls. Further analysis showed positive correlations between IL-6 levels and BMI, symptom duration, and age.

The team’s findings suggest that patients with LBP have low-grade systemic inflammation and that profiling of circulating cytokines can assist in improving diagnosis of LBP. “We’re very excited by the results of this clinical study and will continue to study cytokine levels in the future,” said Dr. Chahine.

The study, by Weber KT et al., was published January 7, 2016, in the journal Arthritis Research and Therapy.

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The Microlab 400 system is semi-automated, programmable, and optimized with reagents to deliver reliable results. It is designed to help decrease lab errors and increase productivity, and is considered a cost-effective solution for primary, STAT or backup needs.

The ThinPrep 5000 Autoloader system allows users to load up to 160 ThinPrep Pap, non-Gyn and UroCyte samples for up to eight hours of walk-away processing. It also features integrated slide etching, which reduces time spent manually applying slide labels and potential labeling errors.

The GloCyte automated cell counter system is designed to determine the quantity of RBCs and total nucleated cells in cerebrospinal fluid. It uses 30 microliters of sample per test and features disposable test cartridges, built-in QC of Levey-Jennings charts, and an audit table.

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PCR-Based Blood Test Diagnoses Rare Childhood Germ Cell Cancer team of British researchers has developed a noninvasive, low cost blood test for the diagnosis of rare childhood germ cell cancer.

The five year disease-free and

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overall survival rates for patients with high-risk malignant germ cell tumors are less than 50%, so improved diagnostic and monitoring techniques are required to improving outcomes for patients. Currently, biopsy is the most

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commonly used diagnostic method, but this technique is prone to sampling errors and may not be representative of the tumor as a whole. Computerized tomography (CT) scans and magnetic resonance imaging (MRI) also provide useful information but are not diagnostic and do not discriminate between benign and malignant tumors.

Investigators at the University of Cambridge (United Kingdom; www. cam.ac.uk) have now described a noninvasive, low cost blood test for the diagnosis of germ cell tumors.

This test is a qRT–PCR (quantitative real-time PCR [polymerase chain reaction]) profiling analysis of the microRNAs miR–371–373 and miR–302/ 367 cluster miRNAs, which are overexpressed in all malignant germ cell tumors. Some of these miRNAs show elevated serum levels at diagnosis.

MicroRNAs (miRNAs) are a class of about 20 nucleotides-long RNA fragments that block gene expression by attaching to molecules of messenger RNA (mRNA) in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA. With their capacity to fine-tune protein expression via sequence-specific interactions, miRNAs help regulate cell maintenance and differentiation.

The investigators used their assay to evaluate a total of 45 serum and CSF samples, obtained from 25 pediatric patients. They found that a four-

serum miRNA panel (miR–371a–3p, miR–372–3p, miR–373–3p, and miR–367–3p): (i) showed high sensitivity/specificity for diagnosing pediatric extracranial malignant germ cell tumor; (ii) allowed early detection of relapse of a testicular mixed malignant germ cell tumor; and (iii) distinguished intracranial malignant germ cell tumor from intracranial non-germ cell tumors at diagnosis, using CSF and serum samples.

“Although relatively rare, childhood germ cell tumors need to be diagnosed accurately and followed up carefully to give us the best chances of treating them,” said senior author Dr. Nicholas Coleman, professor of pathology at the University of Cambridge. “At the moment, we are not good enough at diagnosing these tumors and monitoring their treatment: we need better, safer, and more costeffective tests.”

The study was published in the December 15, 2015, online edition of the British Journal of Cancer.

Image: A micrograph of a seminoma, a common germ cell tumor (Photo courtesy of Wikimedia Commons).

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The Accellix is a four-color system with single-use disposable cartridges and automatic data analysis for population identification and/or cell surface marker quantification. The system is easy to use, considered ideal for multiple applications, and works easily with whole blood.

The LeadCare Plus is a user-friendly system that requires minimal training/experience, and offers electronic calibration that takes seconds to complete, with no standards and no drift. The system includes pre-packaged consumables, and features an optional data management system.

The FREND system is a quantitative immunoassay-analyzing instrument that utilizes disposable cartridges to provide in vitro diagnostics results.

Benefits include a compact design, small sample volume analysis, innovative microchip technology, and a flexible platform for multiple tests.

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Zika Virus Tied to Potential Brain Damage in Newborns he Brazilian authorities are investigating thousands of suspected cases of microcephaly in babies born to mothers infected with the mosquito-borne Zika virus, while they were pregnant.

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Zika is a virus that is transmitted by the same Aedes mosquito that spreads dengue and chikungunya and infected people have clinical symptoms similar to those illnesses and it is possible that some suspected cases

of dengue could be Zika.

Scientists at the Ministry of Health (Brasilia, Brazil; www.fns.saude.gov. br) have been investigating potential links between Zika virus infection in pregnancy and fetal microcephaly since October 2015, when they reported an unusual surge in cases of microcephaly in newborns following a Zika virus outbreak in the northeastern states. Up to December 12, 2015, the Brazilian ministry had been notified of 2,401 suspected cases of microcephaly linked to Zika virus infection in pregnancy. Of these, 2,165 are under investigation, 134 have been confirmed and 102 have been discarded.

The most common symptoms of Zika infection are mild fever, rash, headache, joint pain and non-purulent conjunctivitis, which is red eye with no pus. One out of four people may not develop symptoms, but those who do, experience them from two to seven days. Severe disease requiring hospitalization is uncommon.

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smaller-than-normal head, caused by abnormal brain growth or because the brain stops growing. The brain fails to grow as the infant develops, and the condition often results in serious neurological and development problems and sometimes early death.

By December 22, 2015, a team at the Institute of Biomedical Sciences (ICB) at the University of Sao Paulo (Brazil; www.usp.br) had already developed cultures for growing Zika in cells, a necessary first step for experiments and for obtaining diagnoses via DNA. Within a month, they expect to have a blood test for diagnosing Zika that is cheaper and easier than a DNA test. Angela Rocha, MD a pediatric infectologist, said, “It’s a very personal decision, but at this moment of uncertainty, if families can put off their pregnancy plans, that’s what we’re recommending.”

Image: The female Aedes aegypti mosquito that transmits the Zika virus (Photo courtesy of James Gathany/CDC).

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Protein Levels May Help Diagnose Bipolar Disorder cont’d from cover

as the treatments differ and a medication suited to one condition may be dangerous to patients with another.

Up to now psychiatrists have relied on observed symptoms and patient assessments based on interviews, and that information is then compared to established diagnostic criteria.

Psychiatrists at the Mayo Clinic, Rochester, MN, USA; www.mayo. edu) recruited study volunteers, 46 had been diagnosed with bipolar I (history of mania) depression, 49 with bipolar II (history of hypomania) depression, and 52 with unipolar depression. They were compared with 141 individuals without mood disorders, known as controls. A urine drug screen was performed by study personnel using a One Step Multi-Drug Urine Test Panel kit (W.H.P.M.; Irwindale, CA, USA; www.whpm. com) to screen for any current illicit substances after participants signed the study consent form.

About 288 serum samples (141 controls, 52 unipolar, 49 bipolar II, 46

bipolar I) were randomized to four plates (72 wells × 4). There was no difference in plate by group allocation and age of sample from collection to analysis. The 320 proteins (were measured in 250 L serum samples using the DiscoveryMAP multiplexed immunoassays (Myriad RBM Inc.; Austin, TX, USA; www.rbm. myriad.com).

In total, after adjusting for variables, 73 proteins were found to differ among the four groups studied.

The results however showed a significant difference for six proteins in individuals with bipolar I depression (BP-1) versus controls. These were growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR).

GDF-15, RBP-4 and TTR were good predictors of BP-I with ROC-AUC of 0.81, while HPX and HPN were fair predictors of BP-I with ROC-AUC of 0.74 and 0.78, respectively.

Mark A. Frye, MD, head of psy-

chiatry and lead author of the study said, “The potential of having a biological test to help accurately diagnose bipolar disorder would make a huge difference to medical practice.

It would then help clinicians to choose the most appropriate treat-

ment for hard-to-diagnose individuals.” The study was published on December 8, 2015, in the journal Translational Psychiatry.

Image: The one-step multi-drug urine test panel kit (Photo courtesy of W.H.P.M.).

Blood Levels of Ebola Virus Are Predictive of Death urrently, most treatments used in Ebola treatment centers (ETCs) rely on supportive care, but several experimental therapies are being assessed for Ebolavirus disease (EVD) following promising in vitro and limited in vivo findings.

The relationship between patients’ viremia or viral load and their probability of death has been assessed and how this relationship may be used to explain temporal trends in reported case fatality rates (CFRs) and inform different treatment study designs has been investigated.

Scientists from the Institut Pasteur (Dakar, Senegal; www.pasteur.sn) and their international colleagues used laboratory, clinical, and demographic data for 699 patients with confirmed EVD hospitalized in the Conakry area of Guinea between March 2014 and February 2015 to model the association between viremia and CFR. A blood sample was collected from all suspected EVD patients, and a real-time reverse transcriptase polymerase chain reaction (RT-PCR) test was performed systematically. If the test is positive, the case was confirmed. Viremia was derived

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from the C t value obtained for each sample tested.

The team found the CFR for patients with low, intermediate, and high viremia was 21%, 53%, and 81%, respectively. Compared to adults age 15 to 44 years, children under 5 years old and adults 45 and over had higher CFR, but children aged 5 to 14 had a lower CFR. They also noted that when the average viremia increased tenfold in July 2014, CFR increased as well, by 14%. The authors caution that these findings may not translate to cases outside the hospital setting.

The authors concluded that in a very large and consecutive sample of patients with confirmed EVD, they have shown that viremia is a strong predictor of death that may in part explain previously observed heterogeneity in CFR estimates. Viremia may also provide an important mechanism for risk adjustment among patients in studies aiming to estimate associations of treatment with outcome, and a mechanism to stratify patients into different risk groups within clinical trials. The study was published on December 1, 2015, in the journal Public Library of Science Medicine.

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New Technology Standardizes Screening for Sickle Cell Disease ver half of babies born with sickle cell disease (SCD) in countries with limited resources die before age five and over six million people in West and Central Africa suffer from the disease, which causes pain crises, widespread organ damage and early mortality.

Newborn screening tests can only be performed in central laboratories in developing countries and the results can take several weeks and it may be impossible to reach the parents after they have left the health center. This may delay the onset of important interventions, including immunizations, antibiotics and vitamins and therefore, there is a need for simple, rapid and mobile analyses of hemoglobin types in newborn blood.

Scientists at Case Western Reserve University School of Medicine (Cleveland, OH, USA; www.case. edu) have developed an innovative mobile device, the Hemoglobin-Electrophoresis Biochip or HemeChip, which has the unique ability to rapidly screen for sickle cell disease with

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just a few drops of blood. They utilized a micro-engineered design and microfluidic approach in HemeChip development. Microfluidic technology is a novel tool, which allows small sample volume of less than 20 μL of blood, from a finger or heel prick.

Other attributes of the HemeChip are portability, ease of use, and low power consumption.

The HemeChip, a micro-electrophoretic device, examines and identifies hemoglobins, including hemoglobinopathies sickle cell anemia (HbSS), sickle trait (HbAS) and SC disease (HbSC). The microchip system allows rapid manual assembly and is single use, to prevent potential cross-contamination between patients. HemeChip fabrication is suitable for mass-production, which is critical for translation of point-of-care technologies. At present, the HemeChip material cost is less than USD 5.00, and this cost is likely to decrease if mass-produced.

Jane Little, MD, an associate professor and lead author of the study,

said, “While sickle cell newborn screening is standard in the USA, very few infants are screened in Africa because of the high cost and level of skill needed to run traditional tests. This new mobile technology provides an easy to use, cost-effective tool that takes us closer to standardizing newborn screenings on mobile devices, thus simplifying diagnosis. It could make a huge difference in developing nations worldwide, enabling

early treatment for this disease.” The study was presented at the 57th Annual Meeting of the American Society of Hematology (ASH) held December 5–8, 2015, in Orlando (FL, USA; www.hematology.org).

Image: The HemeChip micro-electrophoretic device that examines and identifies hemoglobins including hemoglobinopathies (Photo courtesy of Case Western Reserve University).

Inherited Gene Mutation Leads to Ovarian Cancer omen who carry an inherited fault in a certain gene are more than three times more likely to develop epithelial ovarian cancer (EOC) than those without the mutation. Risk prediction based on identifying germline mutations in ovarian cancer susceptibility genes could have a clinically significant impact on reducing disease mortality as around 18 women in every 1,000 develop ovarian cancer, but this risk increases to around 58 women in every 1,000 for women with a mutation in a specific gene.

An international team of scientists led by those at the University of Cambridge Cancer Group (UK; www. cancerresearchuk.org) compared the genes of more than 8,000 white European women, which included around 3,250 women diagnosed with ovarian cancer, 3,400 women who did not have cancer and 2,000 women who had a family history of the disease. For each gene, they estimated the prevalence and EOC risks and evaluated associations between germline variant status and clinical and epidemiological risk factor information.

Next generation sequencing was

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used to identify germline mutations in the coding regions of four candidate susceptibility genes: BRCA1 Interacting Protein C-Terminal Helicase 1 (BRIP1), BRCA1 Associated RING Domain 1 (BARD1), Partner and Localizer of BRCA2 (PALB2) and Nibrin (NBN). The scientists found an increased frequency of deleterious mutations in BRIP1 in case patients (0.9%) and in the participants from a clinical screening trial of ovarian cancer (UKFOCSS) (0.6%) compared with control patients (0.09%), but no differences for BARD1, NBN1 or PALB2.

Paul D. P. Pharoah, MD, a professor of Cancer Epidemiology and codirector of the study, said, “Our work has found a valuable piece of the puzzle behind ovarian cancer and we hope that our work could eventually form the basis of a genetic test to identify women at greatest risk. Finding these women will help us prevent more cancers and save lives. This would be important in a disease like ovarian cancer, which tends to be diagnosed at a late stage when the chances of survival are worse.” The study was published in the January 2016 edition of the Journal of the National Cancer Institute.

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Super-Resolution Microscopy Improves Platelet Granule Disorder Diagnosis latelets or thrombocytes form part of the blood, help heal wounds, and prevent bleeding by forming blood clots and they do this through tiny granules that release molecules for blood clotting.

Platelet disorders occur when these granules are too few in number, are misshapen, or do not release the right molecules; and as causes for platelet disorders vary considerably, specific treatment can be improved if diagnostic tests can distinguish the different types.

A team of scientists led by those at the University College London (UK; www.ucl.ac.uk) took blood samples were taken from three patients with Hermansky Pudlak Syndrome and seven controls. The three patients each had a defect in the HermanskyPudlak Syndrome 1 (HPS1) gene, HPS6 and HPS5 respectively and all the controls were healthy volunteers. Platelet-rich plasma was isolated from blood and the platelets were fixed, stained for CD63, and processed for analysis by immunofluorescence microscopy, using a Structured Illumination Microscope (SIM).

The imaging technology was custom-built by the

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team to automatically count the number of granules per platelet, identifying those with Hermansky-Pudlak Syndrome, a rare blood disorder thought to affect 1 in 500,000. The team distinguished the three patients with Hermansky-Pudlak Syndrome from the seven normal controls with 99% confidence. Automated counting of granules showed that those with the disorder had only one third as many granules as controls.

The authors concluded that a super-resolution imaging approach is effective and rapid in objectively differentiating between patients with a platelet bleeding disorder and healthy volunteers.

CD63 is a useful marker for predicting HermanskyPudlak Syndrome and could be used in the diagnosis of patients suspected of other platelet granule disorders.

David Westmoreland, a doctoral student and first author of the study said, “We’ve found that SIM has a lot of advantages over whole mount electron microscopy as a diagnostic method. Samples don’t need to be analyzed live and can be reana-

lyzed, and automation means analysis is unbiased and less time-consuming. Given [that] about 75% of patients with a bleeding disorder such as Hermansky-Pudlak Syndrome are initially misdiagnosed and 28% need to see between four to six specialists before receiving the correct diagnosis, there is a demand for a new method of analysis.” The study was published online on January 25, 2016, in the Journal of Thrombosis and Haemostasis.

Image: Platelet granules in a blood sample stained for the marker protein CD63 visualized by Structured Illumination Microscopy (Photo courtesy of the University College London).

TB Tests Assessed to Diagnose Pregnant HIV Positive Women he most commonly used test for tuberculosis (TB) fails to accurately diagnose the disease in up to 50% percent of pregnant women who are positive for the human immunodeficiency virus (HIV+).

The performance of latent TB infection (LTBI) tests has been assessed in HIV-infected pregnant and postpartum women, and the immunology behind discordance in pregnancy investigated, and the implications for the development of postpartum tuberculosis explored.

Scientists at the Weill Cornell Medical College (New York, NY, USA; www.weill.cornell.edu) and

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their colleagues form other institutions enrolled 252 women who were in their second or third trimester and receiving care at a public teaching hospital in India. The women received TB testing at enrollment during pregnancy or at delivery. An additional 39 women participated in a longitudinal study to assess how the TB tests were affected by changes in different stages of pregnancy. They were tested at delivery and three months postpartum.

The investigators also collected blood samples to assess for levels of infection-fighting proteins.

The teams screened pregnant women in their 2nd/3rd trimester and at delivery for LTBI using See us at the AACC Clinical Lab Expo, Booth #2943

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the tuberculin skin test (TST) and QuantiFERON Gold interferon gamma release assay (IGRA), (Quest Diagnostics; Madison, NJ, USA; www.quantiferon.com). A subset of antepartum women had longitudinal testing, with repeat testing at delivery and postpartum and additional cytokines measured from the IGRA supernatant. Of 252 enrolled, 71 (28%) women had a positive IGRA, but only 27 (10%) had a positive TST, and there was 75% agreement. When stratified by pregnancy versus delivery, 20% had IGRA+/TST- discordance at each time point. A positive IGRA was associated with known TB contact. Compared to IGRA+/TST+, women with IGRA+/TST- discordance produced significantly less interferon gamma (IFN-γ; 1.85 IU/mL vs 3.48 IU/mL, and less interleukin 2 (IL-2; 46.17 pg/mL vs. 84.03 pg/mL). Five developed postpartum tuberculosis, of which three had IGRA+/TSTdiscordance during pregnancy.

Jyoti Mathad, MD, MSc, the lead author of study said, “We found that QuantiFERON Gold positivity was almost three times higher than the more widely used TST at every time point tested.

Our blood data suggests that pregnant women produce lower levels of the immune chemicals that many TB diagnostics test for. This finding has implications beyond diagnostics. For example, not all pregnant women lose immune control of TB infection. But, currently we have no way of predicting which women are most likely to get sick from the disease. Our findings about these immune chemicals provide a starting point for developing a test that will tell us who in this already high-risk population is at greatest risk of disease and death and is in most need of treatment.” The study was published on January 14, 2016, in the American Journal of Respiratory and Critical Care Medicine.

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Immunochromatographic Tests Evaluated for Novel Norovirus worldwide spread is conceivable as a novel Norovirus emerged in Asia in the winter of 2014/15 and Norovirus diagnostic assays need to be evaluated to investigate if they adequately detect this emerging genotype.

Seven commercially available Norovirus immunochromatographic (IC) tests are available in Europe and all have the capacity to detect strains of genogroup GII.17 in stool, but sensitivities vary and partly depend on the viral load in the samples.

Virologists at the University Hospital of Dijon (Dijon, France; www.chu-dijon.fr) used 10 samples that had been collected from patients affected by five different gastroenteritis outbreaks. One outbreak was related to oyster consumption, while the four others were caused by person-to-person transmission. Three of the four latter outbreaks had occurred in nursing homes and the fourth in a hospital. All 10 samples had been previously shown to be GII.17 Norovirus-positive by sequencing of the ribonucleic acid (RNA)-dependent RNA polymerase (RdRp) region and the Nterminal/shell (N/S) region.

All seven commercial IC tests were performed according to the manufacturers’ instructions. Due to limited amounts of sam-

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ples, one assay per test was done, except when the results were negative, in which case they were controlled by a second assay when possible. The virus copy numbers were quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR) on the same day. Measurements of the virus titers in each sample allowed to demonstrate that a positive result could be obtained with most of the IC tests (five in seven) if the samples presented a minimal load of 4.88 × 108 virus copies/g of stool. The lowest viral load detected by an IC test was 6.54 × 106 copies/g of stool and this gave a weak positive signal with the RidaQuick Norovirus test (R-Biopharm AG, Darmstadt, Germany; www. r-biopharm.com). Three samples in the study, all of which had relatively high viral loads of greater than 1.34 × 109 copies/g of stool nevertheless gave negative results with some of the tests.

The authors concluded that the seven IC tests evaluated were able to detect GII.17 with various sensitivities due to virus titers, and possibly antigenic differences and kit design. Therefore some IC tests may need to be optimized for the detection of Norovirus genogroup GII.17. The study was published on January 28, 2016, in the journal Eurosurveillance.

Image: The RidaQuick rapid immunochromatographic test for Norovirus (Photo courtesy of R-Biopharm AG).

Early and Accurate Prediction of Leukemia Made Possible cute myeloid leukemia (AML) is the most common type of leukemia in adults and recent studies demonstrate that early and accurate prediction of this aggressive cancer is possible how it will develop in individuals.

Scientists have been able to fingerprint myelodysplastic syndromes (MDS), a state for blood cells that turns into AML cancer in approximately 30% of pa-

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tients. The study demonstrates that early and accurate prediction of this aggressive cancer is possible.

Scientists at McMaster University (Hamilton, ON, Canada; www.mcmaster.ca) collaborated with those at the University of Bologna (Italy; www. unibo.it) to perform a retrospective study on human blood samples that had been previously collected from patients with MDS, some of whom

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eventually developed AML. Gene expression analysis of patient blood samples was accurate in predicting which patients would develop AML and which would not.

The study revealed that removal of glycogen synthase kinase-3α (GSK-3α) and GSK-3β dependency leads to aggressive AML. Although GSK-3α deletion alone has no effect, GSK-3β deletion in hematopoietic stem cells (HSCs) resulted in a preneoplastic state consistent with human myelodysplastic syndromes (MDSs). Transcriptome and functional studies reveal that each GSK-3β and GSK-3α uniquely contributes to AML by affecting Wnt/Akt/mTOR signaling and metabolism, respectively. The molecular signature of HSCs deleted for GSK-3β provided a prognostic tool for disease progression and survival of MDS patients. The study revealed that GSK-3α- and GSK-3β-regulated pathways can be responsible for stepwise transition to MDS and subsequent AML, thereby providing potential therapeutic targets of disease evolution.

Mickie Bhatia, PhD, a professor and lead investigator, said, “This discovery improves our ability to identify which patients with MDS will develop AML. However, our next step is to go beyond better predictive measures for the development of a blood cancer, and use this predictive gene expression as a target for drugs to prevent AML from developing altogether. This will be part of a new era of genetic-based drug discovery.” The study was published on January 11, 2016, in the journal Cancer Cell.

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PRODUCT NEWS ORAL FLUID COLLECTION SYSTEM

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The NeoSal system is designed for maximum ease of use when collecting oral fluid samples. It has a stimulant-free absorbent pad with a built-in sample volume adequacy indicator, and contains a buffer to maximize sample stability and recovery of drug analytes from the pad.

The NG Whole Blood hCG Test is a rapid visual immunoassay for the qualitative presumptive detection of human chorionic gonadotropin in human whole blood to aid in the early detection of pregnancy. The test requires only 20 µL of whole blood, and provides results in five minutes.

The PROTIA Allergy-Q is an in vitro diagnostic test for the semi-quantitative determination of allergenspecific IgE concentrations in human serum or plasma. The multiplex allergy diagnostic kit uses PLA technology, and can detect up to 64 markers in one panel.

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Potential Biomarker Found for HER2+ Breast Cancer Recurrence new study indicates that T-cells that recognize HER2 receptor may be key to developing an immune signature test to identify and monitor HER2-positive breast cancer (HER2BC) patients at high risk of treatment failure and recurrence.

Recurrence of HER2-BC after treatment may be due to a specific, and possibly cancer-induced, weakness in the patient’s immune system – a weakness that in principle could be corrected with a HER2-targeted vaccine – according to a new study by researchers at the Perelman School of Medicine, University of Pennsylvania (Philadelphia, PA, USA; www.med.upenn.edu). T-cells from patients whose breast cancer had recently recurred showed far weaker response to the HER2 receptor protein, compared to T-cells from patients whose breast cancer had not recurred over a long period following treatment. The study

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suggests that patients with HER2-BC – which accounts for roughly 20% of the 260,000 invasive breast cancers diagnosed yearly in the US – might someday undergo immune status monitoring with blood tests before, during, and after treatment, to help gauge the risk of recurrence, and possibly to reduce that risk with therapies that boost anti-HER2 immunity.

“We know that it’s not a fixed immune defect, because we have several clinical trials open where we’re vaccinating people and can restore anti-HER2 responsivity,” said senior author Prof. Brian J. Czerniecki, MD, PhD. Czerniecki and colleagues have long been investigating the role of the immune system in breast cancer, and the potential of cancer vaccines. Their recent focus has been on the T-helper type 1 (Th1) immune response. In the new study, the team isolated immune cells from 95 women with invasive

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HER2-BC, and analyzed the cells’ ability to mount a Th1 response against the HER2 growth factor receptor protein. HER2-BC cells overexpress the HER2 receptor, which helps drive their rapid proliferation. The cells from women with recently recurrent cancer that had not yet been re-treated had only about 10% of the anti-HER2 responsivity compared to that seen in women whose HER2-BC had not recurred for at least 2 years following treatment. Across all the patients, the researchers found that patients with the least amount of responsivity had experienced only 47 disease-free months after treatment, on average, compared to 113 diseasefree months for the patients in with the most responsivity.

The low anti-HER2 responsivity seen in the women with recurrent cancer was not part of a broader immune suppression. “We detected no other immune deficit – just the deficit in the anti-HER2 response,” said Prof. Czerniecki.

The findings complement those from two studies published earlier by Czerniecki and colleagues.

In one, Th1 responsivity against HER2 tended to vary strikingly from high responsivity in cancer-free and early-stage HER2-BC patients, to low responsivity in advanced HER2-BC patients. In the other study, patients whose tumors shrank during standard pre-surgery drug treatment had much stronger anti-HER2 responsivity, compared to patients whose tumors responded less completely to that drug treatment.

How patients lose anti-HER2 responsivity during formation and growth of a HER2-BC tumor is not yet clear. “We’re trying to determine the mechanism, but we already know that we can ‘fill the tank’ with vaccines to restore that specific responsivity to HER2,” said Prof. Czerniecki. In addition, the team hopes to confirm the association between anti-HER2 responsivity and cancer recurrence risk in larger clinical trials that would track patient immune status over time.

The study, by Datta J. et al., was published online December 30, 2015, in the journal JAMA Oncology.

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PRODUCT NEWS PANCREATIC ELASTASE ELISA

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The Pancreatic Elastase ELISA is designed for the quantitative determination of human pancreatic elastase in stool as an aid in the diagnosis of the exocrine pancreatic function. The ELISA allows for a quick and reliable diagnosis, and follow-up of an exocrine pancreatic insufficiency.

The cobas t 411 offers the highest reagent capacity among analyzers designed for low-volume coagulation labs. Additional benefits include continuous loading of samples, reagents and cuvettes; a unique cuvette design; multimode cap piercing; and maximum reagent utilization from tilted vials.

The Tacta range features a balanced design that is easy, safe and comfortable to use. The pipettes are available in a range of volumes from 0.110,000 µL in single-channel models, and from 0.5300 µL in multichannel models, and deliver consistent and accurate results time after time.

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Diagnostic Method Created Based On Birefringence new diagnostic method has been created based on birefringence, which is the ability of substances to change the polarization state of light. With this method, doctors around the world could easily, rapidly, and reliably detect pathogenic microorganisms.

Although the concept behind this new technology is very general and appears so easy to operate, the scientific basis underlying the invention is extremely complex. The phenomenon of birefringence of polarized light from the lipid based lyotropic liquid crystals, which consist of self-assembled structures of fat molecules in water.

Scientists at the Swiss Federal Institute of Technology (ETH; Zurich; Switzerland; www.ethz.ch) used lipidic cubic phases that are optically isotropic, transparent lyotropic liquid crystals (LC), containing highly confined water nanochannels in-be-

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tween percolating lipid bilayers following defined space groups. Due to this nano-confinement, the water in these systems provides a unique environment for chemical and enzymatic reactions.

During the mesoperoxidase enzymatic reaction, the converted product crystallizes within the mesophase domains, generating a detectable birefringence signal and a new general assay principle is presented for the detection of an unprecedented vast class of analytes using such birefringence as sole optical output signal. The team used polarized light microscopy and a small amount of the cubic phase was analyzed under cross-polarized light using an Axioskop 2 MOT microscope (Zeiss;

Oberkochen, Germany; www.zeiss.com) at 37 °C. The polarization device costs CHF 20, which considerably less expensive when compared with other detection methods.

By exploiting bienzymatic cascade reactions or introducing an enzyme-linked immunosorbent assay based on birefringence (Birefringent-ELISA), this approach was used for real-time detection of exemplary analytes, such as glucose and cholesterol, model pathogenic microorganisms, Escherichia coli, and viruses such as Ebola and human immunodeficiency virus (HIV). The team also showed how the same technology enables the rapid, naked eye screening of malaria infection via in meso detection of hemozoin crystallites. Pathogens can be detected very rapidly, and a reliable result received within less than an hour.

Raffaele Mezzenga, PhD, a professor and lead author of the study said, “The Plasmodium parasite invades erythrocytes and digests hemoglobin. The heme component, which is toxic to the parasites, is crystallized and thus has inherently birefringent surfaces. So it’s not necessary to mark it with antibodies and no enzymatic reaction is required.” The study was published in the November 2015 issue of the journal Advanced Functional Materials.

Image: The birefringence pattern of a sample positive to Ebolavirus infection (Photo courtesy of Jijo Vallooran / ETH Zurich).

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Prostate Cancer Screening Improved

By Repeating Abnormal Tests or more than 20 years, the prostate-specific antigen (PSA) test has been used to help screen for prostate cancer, but in recent years, some task forces have called for this blood test to be abandoned because it leads to many unnecessary biopsies.

Prostate-specific antigen may be elevated because of prostate cancer or as a result of infection, physical activity, or sexual activity. Variation in PSA concentrations can also be due to normal biological fluctuation or analytic and laboratory assay differences. As a result, PSA is sensitive but not specific for detecting prostate cancer, especially when levels are moderately elevated between 4 and 10 ng/mL. Physicians and scientists at The Ottawa Hospital (ON, Canada; www.ottawahospital.on.ca) reviewed the medical records of 1,268 men who had an abnormal (high) PSA test result and were evaluated at the Ottawa Regional Cancer Assessment Centre between 2008 and 2013. In 25% of these men, the second PSA test came back normal. Only 28% of men with conflicting test results underwent a biopsy compared to 62% of men who had two abnormal test results, representing a 55% reduction in biop-

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sies. In addition, only 3% of men with conflicting test results who had a biopsy were diagnosed with cancer within the year, compared to 19% of men who had two abnormal tests, suggesting that the second normal test is important. Repeated PSA test results were normal in 315 patients (24.8%).

Rodney H. Breau, MSc, MD, the senior author of the study said, “It is clear to me that any man with an abnormal PSA test should have this test repeated before a decision to biopsy. Some doctors and patients may be worried about missing a significant cancer diagnosis if they forgo a biopsy after conflicting test results, but our study shows this is very unlikely. It is also important to remember that the PSA test is just one factor we evaluate when deciding to do a biopsy, and these decisions are always made together with the patient, and can be revisited if risk factors change.” According to the Canadian Cancer Society, approximately 24,000 Canadians will be diagnosed with prostate cancer each year and the fiveyear survival rate is 96%. A PSA test costs approx-

imately CAD 30, while a prostate biopsy costs approximately CAD 880. The study was published on December 10, 2105, in the journal Mayo Clinic Proceedings.

Image: A micrograph from a prostate biopsy showing a prostatic adenocarcinoma, conventional (acinar) type, the most common form of prostate cancer (Photo courtesy of Nephron).

Elevated Sex Hormone Levels Raise Risk of Uterine Fibroids omen who have high levels of both testosterone and estrogen in midlife may face a greater risk of developing benign tumors on the uterus called uterine fibroids than women with low levels of the hormones.

Three out of four women develop uterine fibroids by age 50, and fibroids can contribute to irregular bleeding, infertility, pelvic pain, recurrent pregnancy loss and other reproductive complications. The first-line treatment is undergoing a hysterectomy, and there are few other treatment options currently available.

Scientists at the Stanford University School of Medicine (Stanford, CA, USA; www.med.

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stanford.edu) and their colleagues examined hormone levels and the incidence of uterine fibroids in women participating in the Study of Women’s Health around the Nation (SWAN). Among the 3,240 women enrolled at the beginning of the study, 43.6% completed the follow-up visits. During nearly annual visits, participants had their blood tested for estrogen and androgen levels. In addition, the women were asked whether they had been diagnosed with or treated for uterine fibroids.

Endocrine assays were performed with an Automated Chemiluminescence System (ACS)-180 analyzer (Bayer Diagnostics Corporation, Pittsburgh,

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PA, USA; www.bayer.com) using a double-antibody chemiluminescent immunoassay with a solid phase anti-IgG immunoglobulin conjugated to paramagnetic particles, anti-ligand antibody, and competitive ligand labeled with dimethyl acridinium ester. The bioactive form of estrogen (17 estradiol [E2]) was assessed with a modified the rabbit anti-E2-6 ACS-180 immunoassay to increase sensitivity and had a lower limit of detection of 1.0 pg/mL. Bioavailable testosterone (T) was measured using a modified rabbit polyclonal anti-T ACS180 immunoassay.

Among the participants, 512 women reported having a single incidence of fibroids, and an additional 478 women had recurrent cases. Participants who had high levels of testosterone in the blood were 1.33 times more likely to develop a single incidence of fibroids than women who had low levels of testosterone. Women who had high levels of testosterone and estrogen faced an even greater risk. Although women with high levels of both hormones were more likely to report a single incidence of fibroids, they also were less likely to have a recurrence than women with low levels of the hormones.

Jennifer S. Lee, MD, PhD, a senior author of the study, said, “Our findings are particularly interesting because testosterone was previously unrecognized as a factor in the development of uterine fibroids. The study opens up new lines of inquiry regarding how fibroids develop and how they are treated. Given that managing uterine fibroids costs an estimated USD 34.4 billion in annual medical expenditures nationwide, it is important to identify new ways to better treat this common condition.

The study was published on December 15, 2015 in the Journal of Clinical Endocrinology & Metabolism.

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LabMedica International

Different Mutations May Predict Different Responses to Chemotherapy mong patients with estrogen receptor (ER)positive, metastatic breast cancer, those who had a D538G and/or a Y537S mutation in the estrogen receptor 1 (ESR1) gene, as detected in cell-free DNA obtained from patient blood samples, had significantly worse median overall survival.

Results from clinical trial showed that adding everolimus to the standard hormonal therapy exemestane improved outcomes for postmenopausal women with ER-positive, locally advanced or metastatic breast cancer that has progressed after treatment with an aromatase inhibitor.

Scientists at the Memorial Sloan Kettering Cancer Center (New York, NY, USA; www. mskcc.org) evaluated blood samples from 541 of the 724 patients enrolled in

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BOLERO-2 clinical trial. They detected the D538G ESR1 mutation in samples from 83 patients, the Y537S ESR1 mutation in samples from 42 patients, and both mutations in samples from 30 patients.

Median overall survival was 32.1 months for patients with neither a D538G nor the Y537S ESR1 mutation, 26 months for those with only a D538G mutation, 20 months for those with only a Y537S mutation, and 15.2 months for those with both mutations. Exploratory analyses showed that adding everolimus to exemestane more than doubled progression-free survival for patients with neither ESR1 mutation and for those with a D538G mutation.

However, the treatment combination did not ap-

pear to increase progression-free survival for patients with a Y537S mutation.

Sarat Chandarlapaty, MD, PhD, a medical oncologist, said, “Using a simple blood test, we found that the D538G and Y537S mutations in the estrogen receptor are more common in patients with advanced, ER-positive breast cancer than previously appreciated and that patients with these mutations don’t respond as well to currently used therapies and die from their disease sooner than patients who do not have these mutations.” The study was presented on December 10, 2015, at the San Antonio Breast Cancer Symposium held in San Antonio, TX, USA; www.sabcs.org).

New Set of External Quality Assessment Programs Launched set of eight new RIQAS external quality assessment (EQA; also referred to as proficiency testing (PT) programs have been launched to provide clinical laboratories with the ability to review calibration issues and systematic errors and to monitor accuracy and bias. They also enable laboratories to assess analytical performance in comparison with other laboratories that employ the same instrument or methods.

Developed by Randox Quality Control of Randox (Crumlin, United Kingdom; www. randox.com), the eight new RIQAS (Randox International Quality Assessment Scheme) EQA programs are: CSF, Sweat Testing, Immunosuppressants, Trace Elements in Serum, Trace Elements in Urine, Trace Elements in Blood, Anti-TSH Receptor, and Cyfra 21-1. Cycles are scheduled to begin in March 2016.

The programs are available in liquid and lyophilized formats, covering the full clinical decision range, reassuring clinicians and patients that the laboratory is releasing accurate, reliable results. Monthly reporting supports rapid identification of errors and implementation of necessary corrective actions, thereby saving on expenses, resources, and valuable time by eliminating the need for patient sample retests. Randox QC’s rapid report turnaround will ensure that results are received within 24–72 hours. If required, corrective actions can then be implemented before the next cycle, providing more peace of mind.

RIQAS is the largest international EQA scheme, used by more than 32,000 laboratory participants in 123 countries. Such a large set of international peer groups provides increased confidence of the statistical validity of the extensive database of instrument and method results.

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PRODUCT NEWS MICROSTRIP READER

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RAPID DIAGNOSTIC TESTS

LABORATORY TEST SYSTEM

Awareness Technology

Coris BioConcept

DIALAB

The Stat Fax 4700 is a stand-alone microstrip reader with an interactive LCD touch screen interface, onboard curve-fitting software, and built-in printer. Its strip carrier accommodates three 12well break-apart microwell strips, and the standard model comes with four filters.

The OXA-48 K-SeT is a rapid diagnostic test for in vitro identification of Carbapenemase OXA-48-like in bacteria culture. It consists of 20 cassettes, 20 tube-droppers and buffer, and requires only five minutes of hands-on time and 15 minutes of reaction time.

The Dialisa 2MP is a fully automated two-plate ELISA operating system for all DIALAB ELISA assays. Key features include rapid pipette speed, learned error recovery, LIS and LIMS compatibility, and QC monitoring with an optional onboard barcode reader for sample identification.

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Prospective Blood Donors Deferred by Hemoglobin Estimation Methodology lood transfusion is an essential part of health care and permits increasingly complex medical and surgical interven-

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Image: The XT 2000i hematology autoanalyzer (Photo courtesy of Sysmex).

tions and dramatically increases the life expectancy and quality of life of patients with a variety of acute and chronic conditions.

In developing countries, it is believed that a large majority of donor deferral could be due to a temporal and correctable cause such as anemia, which is a condition of less than normal levels of healthy red blood cells circulating in the bloodstream and the severity of anemia is measured by a personâ&#x20AC;&#x2122;s hemoglobin level.

Medical laboratory scientists at the University of Ghana (Accra; www.ug. edu.gh) determined anemia in prospective blood donors deferred by the copper sulphate technique of hemoglobin estimation. Venous blood samples were collected into anticoagulant tubes from the subjects who were consenting potential blood donors but failed to meet the requirement for donation due to low hemoglobin level using the copper sulphate technique.

The hemoglobin levels and red cell indices were measured using an automatic hematology analyzer.

A total number of 1,263 prospective blood donors presented to donate blood during the period of this study. Out of these, 1,120 (88.68%) were males and 143 (11.32%) feLINKXPRESS COM

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males. A total of 538 (42.6%) involving 444 males and 94 females were deferred due to varied reasons and 114 (21.2%) of these were due to low hemoglobin (Hb) level. These were assessed for anemia using Hb and red cell indices from a Sysmex 2000i hematology autoanalyzer (Sysmex Corporation; Kobe, Japan; www.sysmex.com) and morphology.

Those with Hb less than 13.5 g/dL for males and Hb less than 12.0 g/dL for females were termed as anemic.

The authors concluded that there was a high prevalence of deferral of prospective blood donors and a significant proportion of these deferred donors were as a result of low Hb levels and subsequently anemia. They suggest that people who fail the copper sulphate procedure of Hb testing should not be just sent way as deferred donors but rather be assessed for anemia and be offered advice and treatment so that if their anemia can be corrected, they are encouraged to come back to donate. The study was published on October 22, 2015, in the journal BMC Hematology.

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LabMedica International

Hyaluronic Acid Turbidimetric Assay Compared to Standard Method irculating hyaluronic acid (HA) in human adults is primarily produced in the peripheral soft connective tissue and transported to the systemic circulation via lymph drainage and the majority of HA is removed from circulation by hepatic elimination. HA is essentially non-immunogenic, which has excluded direct immunochemical methods of measurement.

To accommodate this, several advanced methods of measurements have been used including enzymatic degradation; hyaluronic-binding protein (HABP) linked enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography.

Scientists at the Nordsjaellands Hospital, University of Copenhagen, (Denmark; www.nordsjaellandshospital.dk) and their colleagues measured HA concentrations in 39 samples of serum from 39 randomly selected intensive care unit (ICU) patients. The HA was measured by a particle-enhanced turbidimetric immunoassay (PETIA) and enzyme-linked immunosor-

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bent assay (ELISA) in a 40-sample dilution series and the 39 ICU patients.

The HA was measured with the PETIA (Corgenix; Broomfield, CO, USA; www.corgenix.com) in ICU samples on the Hitachi 917 (Roche Diagnostics, GmbH; Mannheim, Germany; www.roche.com ) and in the dilution series on Modular P (Roche Diagnostics GmbH) analyzers (test assay), and by Corgenix HA ELISA using double determination (reference method).

The scientists found that in the ICU patients, the median HA concentration was 159.0 ng/mL (interquartile range (IQR) 117.5–362.5 ng/mL) with ELISA and 157.5 ng/ml (IQR 92.5–359.6 ng/mL)

with PETIA. The mean difference was 12.88 ng/mL, which was statistically significant and the 95% limits of agreement were −91.17 to 116.9 ng/mL. In the dilution series, the mean difference was −59.26 ng/mL (95% CI, −74.68 to 43.84 ng/mL, and the 95% limits of agreement were 35.23 to −153.8 ng/mL. The authors concluded that there was random variation between the PETIA and ELISA test that could affect performance in a clinical context. The new clinical biochemistry assay for HA determination will allow for large studies of the clinical utility of HA. The study was published online on December 14, 2015, in the Journal of Clinical Laboratory Analysis.

Immunosuppressive Drugs Measured by New Assays wo new clinical autoanalyzer tests for measurement of immunosuppressive drugs have been released to the market.

Roche (Basel, Switzerland; www.roche. com) has announced the market availability of the new Elecsys Sirolimus and Everolimus immunosuppressive drug assays.

These two assays complement the currently available Elecsys Tacrolimus and Cyclosporine assays, and with the mycophenolic acid (MPA) assay complete the Roche Diagnostics immunosuppressive drug-monitoring portfolio.

The Elecsys family of assays offers performance based on Roche’s proven Elecsys heterogeneous immunoassay electrochemiluminescence (ECL) technology.

The tests can be performed on any of the cobas modular platforms, including the cobas 4000 and cobas 6000 analyzer series, or the high-volume cobas 8000 modular analyzer series.

“Immunosuppressive drug monitoring requires a high level of precision to ensure that patients receive the optimal therapy.

The new Elecsys ISD Assays will offer reliable, life-long testing to patients who have had organ transplants,” said Jean-Claude Gottraux, head of professional diagnostics at Roche. “This full offering also provides clinical laboratories with the opportunity to optimize their workflows and consolidate testing for a wide range of relevant markers on a single platform. This is a further example of the Roche commitment to invest in personalized healthcare.”

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PRODUCT NEWS CRITICAL CARE ANALYZER

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CENTRIFUGE

CLINICAL DIAGNOSTICS SYSTEM

Erba Mannheim

Fanem

Hologic

The EBG Stat 820/1020 Menu analyzer combines micro-electronics and micro-sensor technologies and has a throughput of up to 45 samples/hour. It offers a choice of syringe, capillary, and open-tube sample analysis with the option to run auto QC automatically at user-selected intervals.

The Excelsa i 2206 can handle volumes of up to 400 ml, with a minimum speed of 300 rpm and maximum speed of 5,000 rpm. Other features include touch keyboard and LCD screen with elevated display panel, and a cover with double lock and brushless motor.

The Cervista automates the DNA extraction and human papillomavirus detection steps of the Cervista HPV HR test. When combined with the ThinPrep 5000 sample transfer system, it offers a fully automated solution for HPV screening, making it ideal for small- to mid-sized labs.

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Microfluidic Disposable Device Diagnoses Diseases Cheaply he development of a reusable microfluidic device for sorting and manipulating cells and other micro/nano meter scale objects will make biomedical diagnosis of diseases cheaper and more convenient in regions where medical facilities are sparse or cost is prohibitive.

Both bulk acoustic wave (BAW) and surface acoustic wave (SAW) based approaches have shown their competency in the manipulation of macro- to nano- scale objects, regardless of an object’s optical or electrical properties. A wide range of applications in static or continuous flow such as manipulating cells, moving organisms have been demonstrated by either BAW or SAW tweezers.

Scientists at the Penn State University (University Park, PA, USA; www.psu.edu) developed reusable acoustic tweezers to realize acoustic manipulation of cells or particles with a SAW platform

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and disposable superstrate devices. They locally transmitted standing surface acoustic waves into a removable, independent polydimethylsiloxane (PDMS)glass hybridized microfluidic superstrate device for micromanipulation. By configuring and regulating the displacement nodes on a piezoelectric substrate, cells and particles were effectively patterned and transported into the superstrate.

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able method for applications in the fields of pointof-care diagnostics and fundamental biomedical studies. In addition to its use in diagnosing diseases such as human immunodeficiency virus (HIV) and tuberculosis, both of which are endemic in resource-poor regions of the world, the device should find widespread use in hospitals, clinics, biology laboratories and the home due to its low cost and ease of use.

Tony Jun Huang, PhD, a professor and lead author of the study, said, “We believe our acoustic tweezers have tremendous potential, especially in diagnostics, with some applications also in therapeutics. Our current device works well, but to be used in diagnostics, the whole device has to be disposed of after one use. We have now found a way to separate the fluid-containing part of the device from the much more expensive ultrasound-producing piezoelectric substrate. This makes disposable acoustic tweezers possible.” The study was published on October 28, 2015, in the journal Lab on a Chip.

Image: Schematics of the reusable acoustic tweezers device (bottom) with a disposable microfluidic laboratory for cell manipulation and disease diagnosis (Photo courtesy of Penn State University).

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LabMedica International

Nanotechnology Helps Detect Biomarkers for Cancer he detection and quantification of short nucleic acid sequences has many potential applications in studying biological processes, monitoring disease initiation and progression, and evaluating environmental systems.

Nucleic acids consist of chains or sequences of bases stretching from just a few to millions of elements long. The exact order in which these bases are found, even over short distances, is strongly tied to their functions, and therefore can be used as direct indicators of what is going on inside cells and tissue.

Biomedical engineers at the Wake Forest University School of Medicine (Winston-Salem, NC, USA; www.wakehealth.edu) and their colleagues used nanotechnology to determine whether a specific target nucleic acid sequence exists within a mixture, and to quantify it if it does through a simple electronic signature. The team first demonstrated that the technology could effectively identify a specific sequence among a background of competing nucleic acids, and then applied their technique to one particular microRNA (mi-R155) known to indicate lung cancer in humans. They showed that the approach could resolve the minute amount of microRNAs that can be found in patients.

Complementary oligonucleotides were hybridized by incubating the samples at a 1:1 molar ratio in pure deionized water at 95 °C for 10 minutes and gradually cooling to room temperature to generate duplex material (dsBio34 or 23 bp heteroduplex) at a final concentration of 8 M, as confirmed by spectrophotometry. Hybridization was confirmed by gel electrophoresis and Gel images were captured using a Gel Doc system (Bio-Rad Laboratories; Hercules, CA. USA; www.bio-rad.com). Silicon chips (4.4 mm) containing 25 nm thick, free-standing silicon nitride membranes were obtained commercially (Norcada, Inc.; Edmonton, AB, Canada; www. norcada.com) . In each membrane, an individual nanopore (diameter 7.5−9.0 nm) was fabricated using an Orion Plus scanning helium ion microscope (Carl Zeiss; Jena, Germany; www.zeiss.com).

The scientist’s assay based on the solidstate nanopore platform identified specific sequences in solution. They demonstrated that hybridization of a target nucleic acid with a synthetic probe molecule enables discrimination between duplex and singlestranded molecules with high efficacy. The approach required limited preparation of samples and yielded an unambiguous translocation event rate enhancement that can be used to determine the presence and abundance of a single sequence within a background of nontarget oligonucleotides.

Adam R. Hall, PhD, assistant professor of biomedical engineering lead author of the study, said, “We envision this as a po-

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tential first-line, noninvasive diagnostic to detect anything from cancer to the Ebola virus. Although we are certainly at the early stages of the technology, eventually we could perform the test using a few drops of blood from a simple finger prick. If the sequence you are looking for is there, it forms a double helix with a probe we provide and you see a clear signal. If the sequence isn’t there, then there isn’t any signal. By simply counting the number of signals, you can determine how much of the target is around.” The study was published on January 29, 2016, in the journal Nano Letters.

Image: The Gel Doc XR+ system enables quick and easy visualization, documentation, and analysis of nucleic acid and protein gels, blots, and macroarrays (Photo courtesy of Bio-Rad Laboratories).

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PRODUCT NEWS HEMATOLOGY SYSTEM

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CHEMISTRY ANALYZER

HEMOSTASIS SYSTEMS

HORIBA Medical

Hycel Medical

Instrumentation Laboratory

The ABX Pentra 60 C+ offers a throughput of up to 60 samples/hour with only four onboard reagents and one diluent. Other features include three histograms for RBC, BAS/WBC and PLT together with the five DIFF Matrix and counting of Basophils through a specific channel.

The GS200 has a throughput of up to 225 tests/hour (not including ISE) and uses end point, fixed time, and kinetic test methods. It features an enclosed array of spectrometer and photodiodes, and can monitor the reaction time of 81 cuvettes simultaneously.

The ACL TOP Family 50 Series offers sample integrity checks to detect underfilled sample tubes, abnormal sample aspiration, and interference from Hemolysis, Bilirubin or Lipemia. All models feature new lab accreditation tools that document compliance to quality standards.

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Rapid Diagnostic Assay For Ebola Field-Tested apid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance, but diagnosis during Ebola outbreaks in West Africa has relied on polymerase chain reactions (PCR) performed in laboratories outside the region.

Current diagnostic testing is performed by using PCR of ribonucleic acid (RNA) extracted from venous blood samples or swab samples. Although conventional PCRs have high specificity and sensitivity, the time between sampling and obtaining results can be considerable, in particular in settings in which a laboratory with

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PCR capacity is not readily available.

Scientists at the MÊdecins Sans Frontières (MSF; Brussels, Belgium; www.msf.org) and their colleagues obtained blood samples at the same time as the convalescent-phase plasma trial at an Ebola Treatment Center (ETC).

A total of 218 samples from 148 persons were collected during diagnosis, treatment, and convalescence of patients. In the high-risk area, 100- L samples from each EDTA tube were directly transferred by using an automatic pipette with filter tips.

The Xpert Ebola assay (Cepheid Inc.; Sunnyvale, CA, USA; www. cepheid.com) used in the study is fully automated and cartridge based

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(closed system) and includes automated controls for interference with the PCR and adequacy of sample input.

This assay can be used with the Cepheid GeneXpert System, which is widely used for rapid detection of tuberculosis and rifampin resistance in decentralized settings. The only manual step is inactivation of the blood sample and transfer to the Cepheid cartridge; sample processing (RNA extraction), reverse transcription, realtime PCR amplification, and detection of TaqMan probes are then performed automatically.

Of 218 samples tested, the Xpert Ebola Assay identified 26 (12%) positive samples: 8 (5%) of 147 at initial diagnosis, 12 (100%) of 12 after transfusion and six (86%) of seven at convalescence. The routine laboratory identified 18 (69%) of the 26 positive samples identified by the Xpert Ebola Assay. No discordance was observed for diagnostic samples and no samples identified as negative in the Xpert Ebola Assay were identified as positive by the routine laboratory. The eight sam-

ples identified as positive in the Xpert Ebola Assay and as negative by the routine laboratory were five samples obtained during convalescence and three samples obtained after transfusion, had low viral loads and were obtained from four patients.

The authors concluded that that implementation of the Xpert Ebola Assay under programmatic conditions in an MSF ETC in Guinea is feasible and represents a major decrease in time required to obtain results and a possible increase in sensitivity compared with routine diagnostic procedures that use PCR in this setting. Wider implementation of the Xpert Ebola Assay is recommended for facilities capable of supporting safe sampling and patient management if training of laboratory staff and standard operating procedures can be provided. The study was published in the February 2016 issue of the journal Emerging Infectious Diseases.

Image: The Xpert Ebola assay cartridge (Photo courtesy of Cepheid).

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PRODUCT NEWS BENCH TOP INSTRUMENT

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HEMOSTASIS ANALYZER

LAB ANALYZER

Quidel

Haemonetics

Diagnostica Stago

The Solana combines Quidel’s helicase-dependent amplification (HDA) with fluorescence detection to deliver molecular results. It can test a single specimen or batch up to 12 tests at a time, and offers an intuitive, touch screen interface with guided operation and customizable settings.

The TEG Manager allows multiple TEG 6s analyzers to network via a user interface and centralizes data from multiple devices, with remote access to any connected TEG 6s. It contains a TEG Viewer to analyze test results, and a device manager for administration of connected TEG 6s devices.

The STA R Max consists of 215 samples, 70 reagent positions, and 1,000 cuvettes on board.

Other features such as True STAT management for fast TAT and auto verification capabilities makes it ideal for conducting routine and specialized hemostasis assays for all lab organizations.

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Automated Image Analysis Software Reliably Identifies Positive MRSA n a unique-in-its-class digital microbiology study of almost 60,000 samples, new WASPLab software developed for automated colony-scoring of chromegenic media plates provided superior detection of methicillin-resistant Staphylococcus aureus (MRSA).

The groundbreaking results came from an international multicenter study, testing 57,690 samples, where the WASPLab platform software “Chromogenic Detection Module” (CDM) from COPAN Diagnostics, Inc. (Murrieta, CA, USA; www. copanusa.com) detected and segregated positive from negative MRSA samples using chromogenic agar with a sensitivity of 100% and a specificity of 90%–96% (varying by location). The software detected an additional 153 positive MRSA patients that were missed by manual reading.

The study’s sample size and level of sensitivity of 100% “makes this study unmatched in the in-

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dustry,” said Norman Sharples, CEO, Copan Diagnostics.

CDM utilizes an algorithm to identify presence of colonies on a plate and distinguish between different colors to group into negative and positive cultures. The study focused on identifying MRSA using chromogenic agar from 3 different manufacturers (BD Diagnostics, bioMeriéux, Bio-Rad Laboratories) that produce growth with different pigmentation colors. The cultures were read automatically by WASPLab CDM and manually by a laboratory professional. The laboratory professionals were blinded to the software’s results.

CDM’s reading threshold is intentionally set with a high level of prudency designed so it does not miss a positive MRSA culture. In fact, in this large study, CDM never reported any manual positive plates as negative, demonstrating 100% sensitivity. The 90%–96% specificity score varies by loca-

tion due to the conservative threshold of the CDM settings, which set the limitations low in order to avoid any “false negative” interpretation. Most importantly, the data from this study suggests that the CDM software is somewhat more sensitive than manual reading of plate cultures.

The software’s “capability reduces the hands-on time considerably,” said Dr. Sharples, “CDM is not meant to be used without the technologist, but to provide the technologist with valuable tools that rapidly pre-screen cultures, detect the presence of specific organisms of interest or known pathogens, then segregate cultures into positive and negative groups that enable faster turnaround times and actionable results within the therapeutic window.”

The results of the data show that the WASPLab CDM can be used to accurately sort regardless of the chromogenic substrate. Its application for MRSA is only the first step in a series of algorithms developed by COPAN and available to WASPLab users to further the relevance and speed of laboratory results.

The study, by Faron ML et al., was published online ahead of print December 30, 2015, in the Journal of Clinical Microbiology.

Image: An automated colony-scoring of chromogenic media agar plates for the detection of MRSA using the WASPLab image analysis software (Photo courtesy of COPAN Group).

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LabMedica International

Immunomarker Expression Clarified for Thoracic Tumors omprehensive morphological and immunohistochemical subtyping of tumors is of growing importance for therapy selection and propelled the concept of a tumor-specific, individualized treatment. Thoracic pathologists are frequently faced with tissue specimens from intrathoracic/mediastinal tumors and specifically the differentiation between thymic and pulmonary squamous cell carcinomas (SqCC) can be challenging. For non-small-cell lung cancer (NSCLC) the current classification therefore has been extended by the concept of immunophenotyping from biopsies to resection specimens.

Scientists at Heidelberg University (Germany; www.heidelberg.edu) identified a cohort of 1,465 patients for whom formalin-fixed paraffin-embedded specimens of NSCLC were available. Prior to tissue microarray (TMA) construction, a hematoxylin and eosin (H&E)stained slide of each block was analyzed in order to select representative tumor-containing regions.

A TMA machine (AlphaMetrix Biotech; Rödermark, Germany; www.alphametrix.de ) was used to extract a tandem 1.0 mm cylindrical core sample from each tissue donor block. Immunohistochemistry (IHC) was performed with commercially available antibodies and TMA slides were deparaffinized and pretreated with antigen retrieval buffer.

Subsequent steps were performed on a BenchMark Ultra, immunostaining instrument (Ventana, Tucson, AZ, USA; www.ventana.com).

The TMA resection specimens were stained with antibodies against CD117 and CD5.

CD117 was positive in 145 out of 1,457 evaluable cases (9.9%) and CD5 was positive in 133 out of 1,427 evaluable cases (9.3%). Coexpression of CD117 and CD5 was seen in 28 cases (1.9%).

Among the 145 cases that were positive for CD117, 97 (66.8%) were adenocarcinomas (ADC), 34 (23.4%) were SqCC, 5 (3.4%) were adenosquamous carcinomas (ADSqCC), 8 (5.5%) were large cell carcinomas (LC), and one (0.6%) was a pleomorphic carcinoma (PC). In the CD5 positive group consisting of 133 cases, 123 (92.4%) were ADC, four (3.0%) were ADSqCC, three (2.2%) LC and three (2.2%) were PC. None of the 586 SqCC showed expression of CD5.

The authors concluded that a substantial subset of NSCLC exhibit positivity of CD117 and CD5.

Since CD5 expression was not observed in pulmonary SqCC, but is expressed in the majority of thymic squamous cell carcinomas, the application of this immunomarker is a valuable tool in the differential diagnosis of thoracic neoplasms. The study was published on December 8, 2015, in the journal Diagnostic Pathology.

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Image: The Benchmark Ultra staining instrument (Photo courtesy of Ventana).

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PRODUCT NEWS

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AUTOMATED ANALYZER

URINE ANALYZER 77 Elektronika

The UriSed 3 features automatic particle recognition that uses phase contrast as bright-field microscopy.

Additional benefits include LPF-like images that offer zoom option, manual microscopy mode with realtime view capabilities, and a throughput of up to 120 tests per hour.

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CellaVision

The NEXgen is designed for processing microELISA plates and offers flexible configurations between either 600 samples for one assay, or 280samples for up to seven different assays simultaneously. It can also be integrated with a pre-analytical system and LIMS/LIS systems.

The CellaVision DM9600 captures digital images of cells from blood smears and body fluid preparations for routine hematology testing. A loading capacity of 96 slides, continuous feed, and approximately 30 slides throughput/hr makes it ideal for labs with high-volume testing requirements.

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Magnetic Bead Fluorescent Immunoassay Detects Novel Inflammation Marker magnetic bead fluorescent sandwich immunoassay has been developed that allows rapid serum measurement of the novel inflammation marker at the point

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of care (POC) that could aid pneumonia diagnosis.

Pneumonia is an acute infection caused by various bacteria and virus species and the disease is character-

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LAB IMAGING SYSTEM

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ized by augmented bronchoalveolar liquid and pus congesting the respiratory tract, resulting in shortness of breath.

Scientists at the Technische Universität München (Munich, Germany; www. mri.tum.de) obtained healthy blood donor sera, and patient sera were collected from those with radiologically confirmed pneumonia. A rapid and simple magnetic beadbased immunoassay was developed for the detection of the novel biomarker chitinase-3-like protein 1 (CHI3L1), and also known as YKL40, in an innovative POC-ready device for assistance in the diagnosis of pneumonia.

The study was performed using the ESE Quant Tube Scanner device (QIAGEN Lake Constance GmbH; Stockach Germany; www.qiagen. com). Excitation and emission wavelengths were adjusted to 625 and 680 nm, respectively, to fit the spectral properties of the fluorescent 7hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one (DDAO). The ESE Quant Tube Scanner uses a confocal microfluorescence reader, which is small enough to be automatically positioned under each tube. The measurement is repeated every 20 seconds, leading to the recording of the time course of substrate turnover.

The assay procedure, from sample addition to data retrieval, consists of three steps and is performed in less than 20 minutes. The assay has a linear range from 3 ng/mL to 111 ng/mL, with a limit of detection of 2.9 ng/mL. The average recoveries

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were found between 101 and 111%.

The mean calculated serum concentration of patients with pneumonia was 334 ng/mL ± 225 ng/mL (median 300 ng/mL, range 107–821 ng/mL), while serum samples from healthy donors averaged at 50 ng/mL ± 49 ng/mL (median 35 ng/mL, range 9–199 ng/mL).

The authors concluded that the magnetic bead fluorescence immunoassay is a proof of concept that can accurately and rapidly receive protein biomarker data using antibodies bound to magnetic beads in a POC-ready device, providing a simple alternative immunoassay that could help optimize pneumonia diagnosis in low resource settings. The key features of the presented assay are a rapid fluorescence measurement below 20 minutes, a detection limit that corresponds well to the lower reference range of this inflammation serum marker, and usage of an inexpensive and robust device. The study was published in the December 2015 issue of the Journal of Immunological Methods.

Image: The ESE Quant tube scanner (Photo courtesy of Qiagen).

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Novel Method Enables Simultaneous 96-Well Extraction of Urine Samples for LC-MS/MS Analysis new application note describes a highthroughput semi-automated method for rapid processing of urine samples for LCMS/MS molecular detection and identification, including for drugs-of-abuse analysis.

Using the VIAFLO 96 electronic pipette from INTEGRA Biosciences AG (Zizers, Switzerland & Hudson, NH, USA; www.integra-biosciences.com) with

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Gene Mutation Provides Clue to Vibratory Urticaria atients with autosomal dominant vibratory urticaria have localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum.

Genetic mutation have been discovered that underlies this rare disorder which manifests as itchy red welts, or hives, and other allergic symptoms such as flushing, headaches, fatigue, blurry vision or a metallic taste in the mouth can then occur. Although these symptoms normally fade within an hour, the reaction may occur several times a day.

Scientists at the US National Institutes of Health (NIH; Bethesda, MD, USA; www.nih.gov) evaluated three families who have experienced the disorder through several generations. The evaluation included a forearm vortex challenge, serum histamine measurements, and findings on skin biopsies. They performed genetic analysis of the families with vibratory urticaria by means of linkage scans, exome sequencing, and Sanger sequencing.

Serum histamine levels were measured from serial blood draws during the 60-minute post vortex challenge period using a competitive enzyme immunoassay (SPI-Bio; Montigny le Bretonneux, France; www.bertinpharma.com). Serum tryptase levels from the same time points were measured using the ImmunoCAP 100 system (Phadia; Uppsala, Sweden; www.phadia.com). Immunohistochemistry was performed using the Discovery XT instrument with RedMap detection kit (Ventana Medical Systems; Tucson, AZ, USA; www.ventana.com). Polymerase chain reaction (PCR) and Sanger sequencing were performed according to standard protocols. The teams carried out DNA sequencing on 36 affected and unaffected members of the three families.

The scientists found a single mutation in the Adhesion G Protein-Coupled Receptor E2 (ADGRE2) gene that was shared by family members with vibratory urticaria but not present in unaffected people. The ADGRE2 gene provides instructions for production of ADGRE2 protein, present on the surface of several types of immune cells, including mast cells. In ADGRE2, there is a beta subunit inside the cell’s outer membrane and an alpha subunit on the outer surface of the cell. Normally, these two subunits interact, staying close together, but in people with vibratory urticaria, the team observed a less stable interaction.

When the subunits separate, the investigators believe that the beta subunit produces signals inside mast cells that lead to degranulation. This is what leads to hives and other allergy symptoms. The study was published on February 3, 2016, in the New England Journal of Medicine (NEJM).

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mixed-mode tips from DPX Labs LLC (Columbia, SC, USA; www.dpxlabs.com), samples from a full 96-well plate can be extracted and ready for LC-MS/MS analysis in less than 10 minutes, eliminating the need for a time-consuming evaporation step.

Sample preparation is required to remove matrix interferences from urine samples prior to LC-MS/MS analysis. This procedure is typically very time-consuming and is generally the “bottleneck.” DPX extraction is a highly reproducible and sensitive dispersive SPE method that requires much less solvent compared to other SPE techniques.

INTEGRA and DPX have prepared an application note that describes use of the method to process urine samples for drugs-of-abuse analysis by LC-MS/MS. It describes how the INTEGRA VIAFLO 96 electronic pipette was used to simultaneously undertake, in wells of a 96-well plate, the various steps of the DPX protocol (analyte binding, resin washing, analyte elu-

tion). Results from this semi-automated method are shown to be linear, accurate, and reproducible. All correlation coefficients for the protocol were greater than 0.99 for the range of 12.5–400 ng/mL. INTEGRA VIAFLO 96 is a handheld 96-channel electronic pipette that enables precise, and easy simultaneous transfer of 96 samples from microplates without the cost of a fully automated system. The pipette requires no special skills or training to operate it. Fast replication or reformatting of 96-well plates and high-precision transferring of reagents, compounds, and solutions to or from microplates with the VIAFLO 96 is as easy as pipetting with a standard electronic pipette into a single tube. Four heads with pipetting volumes up to 12.5, 125, 300, or 1,250 μL are available. These pipetting heads are interchangeable within seconds, enabling optimal matching of the available volume range to the application performed.

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Human Polyomaviruses Screened in Cancer Samples new method to screen tumor samples for the presence of any Human polyomavirus has been created and although human polyomaviruses are commonly found in the population, they generally do not produce noticeable symptoms.

One type of Human polyomavirus (HPyV), the Merkel cell polyomavirus (MCV), is known to cause a rare form of skin cancer called Merkel cell carcinoma, and other members of the polyomavirus family can induce non-cancer related diseases in people with compromised immune systems.

Scientists at the University of Pittsburgh Medical Center (PA, USA; www.medschool.pitt.edu) developed a screening protocol that relied on a cocktail of antibodies that can recognize a specific protein expressed by all polyomaviruses. They screened over 1,000 tumor samples, including cases of lung carcinoma, bladder carcinoma, brain tumors, colon cancer, breast cancer, and malignant melanoma.

The investigators used various methods in their screening protocol that included maintaining cell

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lines and plasmids; generating HPyV early region expression constructs; hybridoma production; immunohistochemistry (IHC); rolling circle amplification, genomic DNA isolation and sequencing. To isolate DNA from formalin-fixed paraffin sections, tissue samples were collected in a microfuge tube and incubated in 1 mL of xylene on a rotator for 15 minutes. Western blots for proteins were visualized by Odyssey imaging system (LI-COR; Lincoln, NE, USA; www.licor.com).

The team developed P-PIT, an IHC-based panHPyV-screening method to facilitate the detection of PyV early gene products in tissue samples or arrays. The combination of three different PyV-specific antibodies enabled detection of overexpressed T antigens from all HPyVs reported to date by immunoblotting and IHC methods. The study found no evidence for the involvement of human polyomaviruses in the development of other cancers and helps to resolve questions in the field about whether viruses related to Merkel cell polyomavirus contribute to cancer. The technique will also be valuable in studying other diseases in which polyomaviruses are suspected to play a role.

The authors concluded that the pan-HPyVscreening method they established enables detection of T antigens and thus not only allows detection of lytic infection, but also has the potential to uncover HPyV-related oncogenic processes in which late antigens are not expressed. The P-PIT screening assay will be valuable for addressing the perennial controversy of HPyV-related cancer and other disease associations. The study was published on February 25, 2016, in the Journal of Clinical Investigation Insights.

Image: The Odyssey infrared imaging system allows multiplex Western Blotting and accurate protein quantification using fluorescent dyes conjugated to secondary antibodies (Photo courtesy of LI-COR).

Metabolite Profiling Predicts Outcome of Dengue Virus Infection esults of a proof-of-concept metabolomic study supported the potential use of metabolite profiling to predict the outcome of patients with Dengue virus infection.

Dengue fever is a mosquito-borne tropical disease caused by the Dengue virus. Symptoms typically begin three to fourteen days after infection.

This may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash. Recovery generally takes less than two to seven days. In a small proportion of cases, the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously

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low blood pressure occurs.

As epidemics of dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are overwhelming public health capacity for diagnosis and patient care in developing countries, identifying a panel of biomarkers in acute-phase serum specimens for prognosis of severe dengue disease would be of enormous value for appropriate triaging of patients for management.

Investigators at Colorado State University (Fort Collins, USA; www.colostate.edu) decided to take advantage of advances in the field of metabolomics and analytic software to identify host small molecule biomarkers (SMBs) in acute

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phase clinical specimens that could differentiate dengue disease outcomes. Metabolomics is the analysis of low molecular weight biological molecules that result from metabolic processes. Disease states result in changes in metabolism in cells and systems that affect the profile of metabolites.

Analysis of metabolite profiles in disease conditions and comparison with the profiles of non-diseased individuals can be used in diagnosis.

The investigators used hydrophilic interaction liquid chromatography (HILIC)-mass spectrometry (MS) to identify small molecule metabolites that were associated with and statistically differentiated DHF/DSS, DF, and non-dengue (ND) diagnosis groups. They worked with serum samples obtained from dengue patients from Nicaragua and Mexico.

Results revealed that in the Nicaraguan samples, 191 metabolites differentiated DF from ND outcomes and 83 differentiated DHF/DSS and DF outcomes, while in the Mexican samples, 306 metabolites differentiated DF from ND and 37 differentiated DHF/DSS and DF outcomes.

Metabolomic analysis of serum samples from patients diagnosed as DF who progressed to DHF/DSS identified 65 metabolites that predicted dengue disease outcomes. The structural identities of 13 metabolites were confirmed using tandem mass spectrometry (MS/MS).

“Metabolomics provides new opportunities and a powerful approach to investigate potential viral, host, pathogenic, and immunological determinants of dengue infection and pathogenesis,” said Dr. Barry Beaty, professor of virology at Colorado State University.

The work was published in the February 25, 2016, online edition of the journal PLOS Neglected Tropical Diseases.

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Microfluidic Device Automatically Monitors Whole Blood Hemostasis n assay has been devised for testing blood’s clotting tendency, also known as hemostasis, which could one day prove lifesaving in a variety of clinical situations in which a patient’s health is jeopardized by abnormal blood coagulation and platelet function.

The microfluidic based device assay can be used with blood samples or potentially be integrated into patients’ blood flow lines; so that one day clinicians could have the foresight they need to prevent life-threatening events such as blood clotting or internal hemorrhaging.

Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University (Boston, MA, USA; http://wyss.harvard.edu) devised a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples.

The devices were designed to fit on a standard (75 × 50 mm) microscope slide to simplify microscopic analysis using appropriate software and they used SU8 2075 master templates (MicroChem Corporation; Newton, MA, USA; www.microchem. com) fabricated on Si (100) wafers using photolithography. The devices were fabricated using soft lithography of polydimethylsiloxane (PDMS). The device contains hollow channels that mimic the pathology of the narrowing of small blood vessels, which occurs in patients as a side effect of medical conditions or treatments and can often cause a shift in the fluid mechanics of blood flow that can lead to life-threatening blood clots or internal bleeds.

In a large animal study already conducted, the team perfused blood directly from a living vessel into a microfluidic device to measure clinical clotting parameters over time, and they recorded precise predictions for clotting times for blood samples that were far more accurate and faster than currentlyused clinical assays. The real-time monitoring ability of the device could also assess patients’ coagulation status almost continuously, in stark contrast to today’s standard of once or twice a day testing proVISIT US AT: cedures, thereby reducing the likelihood of toxic side effects resulting from anticoagulation thera2016 pies. The team also demonstrated that the device ANNUAL MEETING can detect abnormal platelet function in patients Booth: 2056 with a rare bleeding disorder that cannot be easily identified using conventional assays.

Abhishek Jain, PhD, a postdoctoral fellow and lead author of the study, said, “The physics of what’s happening inside our bodies is a major contributor to the reasons why blood clots form or why clotting fails during surgeries, traumas, or extracorporeal medical procedures. By mimicking the physics of blood clotting in our device more precisely, we hope this technology can one day be used to save lives.” The study was published on January 6, 2016, in the journal Nature Communications.

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Image: A hemostasis monitoring microdevice comprises a microfluidic mechanism with hollow channels through which blood is flowed and a proprietary algorithm for analyzing patient-specific data to predict when blood clots will form (Photo courtesy of the Wyss Institute).

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The Mini Cube continuous loading instrument is designed for the determination of ESR on four samples simultaneously, directly on the hematocrit tube. Measuring 135 x 191 125 mm and weighing 1.5 kg, it features a 480x272 TFT 16.7-inch display, as well as USB and Bluetooth connector.

The Nova provides batch analysis, walkaway automation, and throughput of 475 tests/hr. It uses whole blood/serum/plasma samples for stat/routine testing, as well as CSF and dialysate samples for specialty testing, and urine samples without pre-dilution, recalibration or reprogramming.

The QuikRead go is designed and calibrated for both photometric and turbidimetric measurement for in vitro diagnostic use. It consists of the instrument with an interactive touch screen and readyto-use reagent kits for application in primary healthcare settings.

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Blood Test Could Identify Which Patients Need Antibiotics cute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical car and despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics.

Misuse of antibiotics is a key contributor to antibiotic resistance; if a patient takes antibiotics for a viral infection, the drug will still attack bacteria in the body, but it will attack healthy or beneficial bacteria. This can cause antibiotic-resistant properties that can be passed on to other bacteria.

Scientists at Duke University (Durham, NC, USA; www.duke.edu) and their colleagues investigated whether host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. The observational cohort study determined whether host gene expression patterns discriminate noninfectious from infectious illness and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with

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community-onset acute respiratory infection (ARI) or noninfectious illness, as well as 44 healthy controls, was measured using microarrays.

By measuring patients’ gene expression profiles from blood samples, the team found they could use the previously identified gene signatures to correctly identify patients with influenza viruses, rhinovirus, various streptococci bacteria and other common infections with 87% accuracy. This Overall accuracy from 238 of 273 subjects was concordant with clinical adjudication, which was more accurate than procalcitonin (78%), and three published classifiers of bacterial versus viral infection (78 to 83%). The classifiers developed were externally validated in five publicly available data sets. A sixth publicly available data set included 25 patients with co-identification of bacterial and viral pathogens.

The authors concluded that by applying the ARI classifiers they could define four distinct groups: a host response to bacterial ARI, viral ARI, coinfection, and neither a bacterial nor a viral response.

These findings create an opportunity to develop and use host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance. They note that there is one major limitation, however as at present as it takes around 10 hours to assess a patient’s gene expression profile, but the team says they are in the process of working with developers to create a one hour test that can be used by clinicians.

Christopher Woods, MD, MPH, a professor of medicine and senior author of the study, said, “The ideal scenario, should this test ultimately be approved for broad use, is you would go to the doctor’s office and receive your results by the time you meet with your provider. We are working to develop a test that could be run in most clinical labs on existing equipment. We believe this could have a real impact on the appropriate use of antibiotics and guide the use of antiviral treatments in the future.” The study was published on January 20, 2016, in the journal Science Translational Medicine.

Blood Test Monitors DNA Fragments for Melanoma Metastases blood test which monitors blood levels of DNA fragments from dead cancer cells does a superior job than the current standard test at tracking the severity and potential spread of metastatic melanoma.

The standard test, in widespread use for decades to inform treatment decisions, measures blood levels of the enzyme lactate dehydrogenase (LDH).

Levels of the enzyme tend to spike during aggressive tumor growth, but are also known to rise as part of other diseases and biological functions.

Scientists at the New York University School of Medicine (NY, USA; www.med.nyu.edu) and their colleagues looks at levels of circulating tumor DNA, or ctDNA, released into the blood when tumor cells die and break apart to spill their contents. They studied 31 patients with inoperable metastatic melanoma, which took three years to complete. All

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had one of the two most common genetic mutations linked to the frequently fatal skin cancer, BRaf Proto-Oncogene, Serine/Threonine Kinase (BRAF) or Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (NRAS). All had ctDNA and LDH blood tests performed after therapy, and most before treatment. Normal blood levels of ctDNA were statistically determined by averaging results from 30 people who did not have melanoma.

The ctDNA levels were determined using droplet digital PCR (ddPCR) assays. Among patients with samples available prior to treatment initiation ctDNA and LDH levels were elevated in 12/15 (80%) and 6/20 (30%) patients respectively. In patients with Response Evaluation Criteria In Solid Tumors (RECIST) scores greater than 5 cm prior to treatment initiation, ctDNA levels were elevated in 5/7 (71%) patients compared to LDH, which was

elevated in 1/13 (8%) patients. In addition, ctDNA levels were elevated in 13/16 (81%) instances of non-RECIST disease progression, including 10/12 (83%) instances of new brain metastases. In comparison LDH was elevated 8/16 (50%) instances of non-RECIST disease progression, including 6/12 (50%) instances of new brain metastases.

David Polsky, MD, PhD, the senior author of the study, said, “Our study results show that circulating tumor DNA is a superior blood test for evaluating and tracking progression of metastatic melanoma. A reliable blood test for tracking potential disease progression is preferred because blood tests offer feedback on what is happening throughout the body, while scans may not always visualize all parts of the body.” The study was published in the January 2016 edition of the journal Molecular Oncology.

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New Data Filtering Tool Helps Identify Pathogenic Mutations new tool designed to assist geneticists to differentiate between pathogenic and harmless mutations is now available on the Internet.

The fraction of the genes that codes for proteins is called the exome, and genome wide analysis has revealed that while the DNA of a patient with a monogenic disease contains about 20,000 variations, only one or two are disease

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Genetic Test Introduced For High-Risk Breast And Ovarian Cancer new 26-gene screening panel, myBRCA HiRisk is a comprehensive High-Risk Breast and Ovarian Cancer (HBOC) screening test specifically designed for high-risk populations has been introduced.

Earlier this year, myBRCA screening test for breast cancer 1/2 (BRCA1 and BRCA2) genes was introduced as the most out-of-pocket affordable breast and ovarian cancer screening test and myBRCA is currently offered in over 20 countries worldwide and received the European CE marking in 2015.

A recently published clinical study performed over 10 years at Massachusetts General, Stanford, and Beth Israel Deaconess hospitals supports the use of this test. The myBRCA HiRisk panel also includes genes known to be associated with Lynch syndrome, Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome and several other genetic syndromes, including Bloom syndrome, Fanconi Anemia, and Ataxia Telangiectasia.

The authors of the study concluded, “In a clinically representative cohort, multigene panel testing for HBOC risk assessment yielded findings likely to change clinical management for substantially more patients than does BRCA1/2 testing alone. This approach may improve clinical outcomes for high-risk individuals and their families and will improve cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes.”

The Veritas Genetics’ (Boston, MA, USA; www.veritasgenetics.com) high-risk panel test identifies germline mutations in 26 genes, including BRCA1 and BRCA2, which are associated with increased risk for developing breast and ovarian cancer as well as other associated cancers. myBRCA HiRisk also tests for structural rearrangements in BRCA1 and BRCA2. myBRCA costs USD 199, does not require insurance authorization and includes genetic counseling and can be performed using a saliva or blood sample.

Joseph V. Thakuria, MD, Genetics Chief Medical Officer at Veritas Genetics, said, “Screening for BRCA1 and BRCA2 mutations, as offered through the myBRCA test, should be the first step in a HBOC cancer prevention regimen for most people. The needs of patients in the high-risk category are served much better with the more comprehensive approach offered with our new myBRCA HiRisk multigene panel.”

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causing. Thus, it is that 58% of rare variants in the protein-coding exome of the general population are located in only 2% of the genes.

To help differentiate between the many harmless variations and the few that are linked to disease, investigators at the Rockefeller Institute (New York, NY, USA; www.rockefeller.edu) developed the gene damage index (GDI). The GDI is a data analysis tool that weighs how frequently the gene is mutated in the general population and calculates the importance of a given gene in a specific disease group, including Mendelian disorders, cancer, autism, and primary immunodeficiencies.

The investigators compared GDI with the leading gene-level approaches, genic intolerance, and de novo excess, and demonstrated that GDI performed best for the detection of false positives (i.e., removing exome variants in genes irrelevant

to disease), whereas genic intolerance and de novo excess performed better for the detection of true positives (i.e., assessing de novo mutations in genes likely to be disease causing).

“To find a needle in the haystack, it helps to get rid of some of the hay,” said first author Dr. Yuval Itan, a researcher in the St. Giles Laboratory of Human Genetics of Infectious Disease at the Rockefeller Institute. “Filtering out the noise, the genes that pollute the data, is crucial. With this method, up to 60% of the irrelevant variants can be removed. The Gene Damage Index will help scientists more easily sort through the large amounts of data produced by next-generation sequencing.”

The GDI study was published in the November 3, 2015, issue of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

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DNA Technology Diagnoses Cases of Tuberculosis Faster he protracted Mycobacterium tuberculosis complex (MTBC) diagnosis and phenotypic drug susceptibility testing (DST) is due to slow growth in culture and contribute to reported treatment initiation delays of 8 to 80 days.

Although genotypic assays can in less than a day identify mycobacterial species and mutations conferring MTBC drug resistance independent of culture, they do not detect all resistance-conferring mutations and are typically still used after microbial culture.

A team of international scientists led by those at The John Radcliffe Hospital (University of Oxford; Oxford, UK; www.ouh.nhs.uk) compared sequencing mycobacteria from all newly positive liquid cultures with routine laboratory diagnostic workflows across eight laboratories in Europe and North America for diagnostic accuracy, processing times, and cost between September 6, 2013, and April 14, 2014. Routine diagnostic procedures at all centers included species identification and culture with isoniazid, rifampicin, ethambutol, and pyrazinamide to establish drug susceptibility.

The teams sequenced specimens once using local MiSeq platforms (Illumina; San Diego, CA, USA; www.illumina.com) and processed data centrally using a semi-automated bioinformatics pipeline.

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They identified species or complex using gene presence or absence, predicted drug susceptibilities from resistance-conferring mutations identified from reference-mapped MTBC genomes, and calculated genetic distance to previously sequenced UK MTBC isolates to detect outbreaks.

The scientists used whole-genome sequencing (WGS) and were able to detect presence of tuberculosis (TB) and whether it was resistant to commonly used antibiotics within one week that is up to eight times faster than utilizing traditional diagnosis methods. Compared with routine results, WGS predicted species with 93% accuracy in 322 of 345 specimens; 356 mycobacteria specimens submitted, and drug susceptibility also with 93% accuracy in 628 of 672 specimens; 168 MTBC specimens identified, with one sequencing attempt. The innovative technology also proved more cost effective, at an average cost of GBP 481 per positive case, compared to GBP 517 per case using current technologies.

Louise J Pankhurst, PhD, the lead author of the study, said, “This is a really exciting time to be working in infectious disease research. The UK is poised to become the first country in the world to

replace traditional tuberculosis diagnosis with whole genome sequencing. Our study has shown how this will dramatically speed up the time taken to diagnose TB, helping patients be placed on the most effective treatment as soon as possible and reducing the risk of disease transmission.” The study was published on December 4, 2015, in the journal Lancet Respiratory Medicine.

Image: The MiSeq next-generation sequencing system (Photo courtesy of Illumina).

Cancer Detected by Dynamic Morphology Tracking on Aptamer-Grafted Surfaces ell motility is a phenomenon where cells move by protruding and contracting sections of the membrane that is a complex process performed through sophisticated balancing act between internal cytoskeleton structure and the cell membrane proteins.

Cancer cells are known to be abnormally flexible compared to healthy cells, primarily due to their inherent weak structures and the forces between the cytoskeleton and the cell surface proteins, which differ between cancerous and healthy cells. The sur-

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face receptors are found in large numbers on the surface of cancer cells.

Scientists at the University of Texas (Arlington, TX, USA; www.uta.edu) and their colleagues have developed a novel cancer cell detection method based on real time cell behavior tracking on engineered surfaces. A synthetic ribonucleic acid (RNA) molecule is coated on chip surface to identify cancer cells. The one-step tumor cell detection approach is based on the dynamic morphological behavior tracking of cancer cells on a ligand-modified surface.

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The human glioblastoma (hGBM) cells showed distinctly enhanced cell movements and activity on the RNA functionalized chips. Every cell on the surface was tracked in real time for several minutes immediately after seeding until these were finally attached. Cancer cells were found to be very active in the aptamer microenvironment, changing their shapes rapidly from spherical to semi-elliptical, with much flatter spread and extending pseudopods at regular intervals.

When incubated on a functionalized surface, the balancing forces between cell surface molecules and the surface-bound aptamers together with the flexibility of the membranes caused cells to show these distinct dynamic activities and variations in their morphologies. On the other hand, healthy cells remained distinguishingly inactive on the surface over the same period. The quantitative image analysis of cell morphologies provided feature vectors that were statistically distinct between normal and cancer cells.

Samir Iqbal, PhD. the principal investigator of the study said, “The initial results hold great potential for applications like cancer screening. A multiple chip based device targeting several proteins can lead to a generic cancer diagnostic platform. The advantage of the technology compared to others is that it is suitable for a quick diagnosis. Once matured, the method has potential to serve as an additional modality to identify tumor cells based on their physical behavior from blood samples or biopsy specimen directly drawn from patients.” The study was published on November 16, 2015, in the journal TECHNOLOGY. LabMedica International June-July/2016

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Simplified Methodology Assists Molecular Analysis of Cholera implified sample preservation methods have been evaluated for molecular characterization using multi-locus variable-number tandem-repeat analysis (MLVA) for differentiation of Vibrio cholerae genotypes.

V. cholerae is endemic in South Asia and Africa where outbreaks of cholera occur widely and are particularly associated with poverty and poor sanitation and knowledge of the genetic diversity of toxigenic V. cholerae isolates, particularly in Africa, remains scarce.

Scientists at the Johns Hopkins University Bloomberg School of Public Health (Baltimore, MD, USA; www.jhsph.edu) and their colleagues collected stool specimens from two geographically distinct outbreaks in the Far North of Cameroon (FNC) in June 2014 and October 2014. Forty-seven V. cholerae isolates and 18 clinical stool specimens after enrichment in broth, from the cholera outbreaks in Cameroon, were preserved on Whatman filter paper for DNA extraction. In addition, a convenience sample of 14 isolates from the Philippines and eight from Mozambique were analyzed.

Cameroonian fecal specimens were screened for V. cholerae O1 and O139 using an enriched dipstick method (Crystal VC, Span Diagnostics; Udhna, Surat, India; www.span.co.in). To evaluate the use of simplified specimen preservation and sample shipping methods, the alkaline peptone water (APW) enriched specimen for each stool was also preserved on Whatman 903 filter paper (GE Healthcare Ltd.; Cardiff, UK; www3.gehealthcare.co.uk) to be tested for V. cholerae using molecular methods. One to two drops of the enriched specimen was aliquoted onto the Whatman filter paper and allowed to air dry; filter papers were stored in individual plastic bags at room temperature until they were sent for DNA extraction and polymerase chain reaction (PCR) processing.

All 87 DNAs were successfully analyzed including 16 paired samples, one a cultured isolate and the other the enriched specimen from which the isolate was collected. Genotypic results were identical between 15 enriched specimens and their culture isolates and the other pair differed at single locus. Two closely related, but distinct clonal complexes were identified among the Cameroonian specimens from 2014. When this simplified DNA

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Image: The Crystal VC Dipstick, a rapid immunochromatographic test for detection of Vibrio cholerae in stool (Photo courtesy of Span Diagnostics).

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preservation method was used, the team was able to molecularly characterize isolates in an on-going outbreak.

The authors concluded that collecting V. cholerae using simplified laboratory methods in remote and low-resource settings allows for subsequent advanced molecular characterization of V. cholerae O1. These simplified DNA preservation methods identify V. cholerae and make possible timely information regarding the genetic diversity of V. cholerae. The study was published on January 6, 2016, in the journal Public Library of Science Neglected Tropical Diseases.

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Multiplex Quantitative Assays Detect Polyparasitism ccurate quantitative assessment of infection with soil transmitted helminths and protozoa are essential to the interpretation of epidemiologic studies of these parasites, as well as for monitoring large-scale treatment efficacy and effectiveness studies.

As morbidity and transmission of helminth infections are directly related to both the prevalence and intensity of infection, there is particular need for improved techniques, such as polymerase chain reaction (PCR) methodology, for assessment of infection intensity for both purposes.

An international team of scientists led by those at the QIMR Berghofer Medical Research Institute (Herston, Australia; www.qimrberghofer.edu.au) collected fecal samples from a total of 680 people,

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originating from rural communities: 467 from samples Timor-Leste and 213 samples from Cambodia. DNA was extracted from stool samples and subject to two multiplex real-time PCR reactions, the first targeting both helminths and protozoa. Samples were also subject to sodium nitrate flotation for identification and quantification of soil transmitted helminth (STH) eggs, and zinc sulfate centrifugal flotation for detection of protozoan parasites.

DNA extraction was performed using the Powersoil DNA Isolation Kit (Mo Bio, Carlsbad, CA USA; www.mobio.com). Extracted DNA was run in two pentaplex real-time PCR reactions. The first was a quantitative assay for Necator americanus, Ancylostoma spp. (A. duodenale, A. ceylanicum), Ascaris spp., Trichuris trichiura; the second was a semi-quantitative assay for Entamoeba histolytica, Cryptosporidium spp., Giardia duodenalis, and Strongyloides stercoralis. The Rotor-Gene 6000 (Qiagen, Melbourne, Australia; www.qiagen.com) was used for all PCR assays, with reactions set up for both PCR reactions.

Higher parasite prevalence was detected by multiplex PCR (hookworms 2.9 times higher, Ascaris 1.2, Giardia 1.6, along with superior polyparasitism detection with this effect magnified as the number of parasites present increased (one: 40.2% vs.

38.1%, two: 30.9% vs. 12.9%, three: 7.6% vs.

0.4%, four: 0.4% vs. 0%). Although, all STH posi-

tive samples were low intensity infections by microscopy as defined by official guidelines the DNAload detected by multiplex PCR suggested higher intensity infections.

The authors concluded that multiplex PCR, in addition to superior sensitivity, enabled more accurate determination of infection intensity for Ascaris, hookworms and Giardia compared to microscopy, especially in samples exhibiting polyparasitism. The superior performance of multiplex PCR to detect polyparasitism and more accurately determine infection intensity suggests that it is a more appropriate technique for use in epidemiologic studies and for monitoring large-scale intervention trials. The study was published on January 28, 2016, in the journal Public Library of Science Neglected Tropical Diseases.

Image: The Powersoil DNA isolation kit (Photo courtesy of Mo Bio).

Tumor Biopsies with Blood Monitoring Show Lesion-Specific Response etastatic tumors driven by drug-targetable genetic mutations become resistant to a targeted therapy drug and the usual practice is to biopsy a single metastatic lesion to test for new mutations that can guide the selection of nextline therapies. A single-lesion biopsy at disease progression may vastly under represent the molecular heterogeneity of resistant tumor clones in an individual patient and may fail to detect the existence of distinct but important resistance mechanisms that could affect treatment responses.

Scientists at the Massachusetts General Hospital (Boston, MA, USA; www.massgeneral.org) and their Italian colleagues collected blood and tumor specimens from a patient with colorectal cancer metastatic to the liver, who responded to an epidermal growth factor receptor (EGFR) antibody drug cetuximab (Erbitux) for 15 months. When the patient’s disease became resistant to therapy, a biopsy of a single liver metastasis was performed to analyze for new, resistance-conferring mutations.

The biopsy specimen was found to have a mito-

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gen-activated protein kinase kinase (MEK1) mutation that had not been present before cetuximab treatment, and the authors demonstrated that MEK1 mutation could drive resistance to EGFR antibodies in laboratory models of colorectal cancer.

Based on those findings, the patient was treated with a combination of the MEK inhibitor trametinib (Mekinist) and another EGFR antibody panitumumab (Vectibix), a combination that had been effective in a cellular model of cetuximab-resistant tumor cells with the same mutation.

Ryan Corcoran, MD, PhD, translational research director, and co-corresponding author of the study, said, “Our conclusion is that the standard practice of performing molecular testing on a biopsy from a single metastatic lesion may be inadequate and that circulating tumor DNA testing may better capture the molecular diversity in a patient’s tumor, enhancing our ability to select effective therapies to overcome resistance.” The study was published on February 1, 2016, in the journal Cancer Discovery.

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New Method Designed to Screen Cancer Cells screening method has been developed that utilizes viscoelastic characteristics to classify many more different types of cancer cells and that could ultimately lead to better treatments for a variety of other diseases.

The method called parallel microfiltration may also have broader applications, including the ability to screen molecules that can alter particular genes and protein levels inside a cell, which could be useful in treating cancer, diabetes, malaria and other diseases.

Scientists at the University of California – Los Angeles (UCLA; CA, USA; www.ucla.edu) placed a mixture of cells and liquid on a porous membrane, and applied air pressure to force the mixture down through tiny pores that have a smaller circumference than the cells. Stiffer cells block the pores so that not much liquid can filter through; for squishier cells, more of the cell-and-liquid mixture passes through. The scientists can use parallel microfiltration to test many different small molecules at once by measuring the filtration of fluid into individual compartments.

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The team found that drug-resistant human ovarian cancer cells are softer than their drug-sensitive counterparts, and that more-invasive cancer cells are softer than less-invasive ones. In future studies, the investigators hope to establish whether squishier cancer cells are in fact more harmful than stiffer cancer cells, and whether their softness can be reversed.

Amy C. Rowat, PhD, the lead author of the study, said, “We want to screen cells based on their squishiness or stiffness. We created a technology to probe the deformability of hundreds of cell samples at the same time, so we can identify compounds that make the cells stiffer. Our hope is that we can identify new compounds that can help to prevent the spread of cancer.” The study was published on December 2, 2015, in the journal Scientific Reports.

Image: An illustration of the components of the parallel microfiltration system (Photo courtesy of UCLA).

Nosocomial Environmental Contamination by MERS-CoV Investigated lthough Middle East Respiratory Syndrome coronavirus (MERS-CoV) is characterized by a risk of nosocomial transmission, the detailed mode of transmission and period of virus shedding from infected patients are poorly understood. The potential role of environmental contamination by MERS-CoV in health care settings and defining the period of viable virus shedding from MERS patients has been investigated using reverse transcription polymerase chain reaction (PCR), and isolating viable virus by cultures.

Scientists at the Chungbuk National University (Cheongju City, Republic of Korea; www. chungbuk.ac.kr) and their colleagues enrolled four laboratory-confirmed MERS patients, hospitalized

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in two hospitals from June 8, 2015, to July 3, 2015.

Respiratory specimens and environmental samples were collected and cultured from all patients during the later stages of clinical disease. Viral ribonucleic acid (RNA) was extracted from all samples and MERS-CoV and the RNA amplified and quantified.

Amplicons were purified and sequenced on an ABI 373 XLDNA sequencer (PerkinElmer; Foster City, CA, USA; www.perkinelmer.com).

Many environmental surfaces of MERS patient rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV. Viral RNA was detected up to five days from environmental surfaces following the last positive PCR from patients’ respiratory specimens.

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MERS-CoV RNA was detected in samples from anterooms, medical devices, and air-ventilating equipment. In addition, MERS-CoV was isolated from environmental objects such as bed sheets, bedrails, intravenous fluid hangers, and X-ray devices. During the late clinical phase of MERS, viable virus could be isolated in three of the four enrolled patients on day 18 to day 25 after symptom onset.

The authors concluded that most of touchable surfaces in MERS units were contaminated by patients and health care workers and the viable virus could shed through respiratory secretion from clinically fully recovered patients. The study was published on December 17, 2015, in the journal Clinical Infectious Diseases.

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Prediabetes Linked to Early Kidney Damage he role of prediabetes as a risk factor for hyperfiltration and albuminuria in persons who do not develop diabetes is unclear and the lack of evidence is mainly due to the difficulty of accurately assessing the glomerular filtration rate (GFR) in the near-normal range of GFR. Diabetes is a major risk factor for kidney disease with around 30% of people with type 1 diabetes and 10%–40% of those with type 2 diabetes will go on to experience kidney failure. New findings suggest that even before a diabetes diagnosis, higherthan-normal blood sugar levels could be causing kidney damage.

Scientists at the University Hospital of North Norway (Tromso, Norway; www.unn.no) and their colleagues studied a sample of 1,627 persons aged 50 to 62 years from the general population without self-reported kidney disease, myocardial infarction, stroke, or diabetes. GFR was measured at baseline and follow-up using single-sample plasma iohexol clearance. Serum iohexol was measured by highperformance liquid chromatography.

Serum creatinine analyses were performed using a standardized enzymatic assay, and cystatin C was measured by particle-enhanced turbidimetric immunoassay. GFR was estimated from creatinine or cystatin C levels. Urinary albumin and urinary creatinine excretion were measured with commercial kits. The albumin-creatinine ratio (ACR) was calcu-

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lated in milligrams per millimole for each urine specimen, and the mean ACR was used in the analyses. HbA1c was measured using liquid chromatography (Variant II instrument; Bio-Rad Laboratories; Hercules CA, USA; www. bio-rad.com), and fasting serum glucose was measured on the Modular model P800 (Roche Diagnostics; Basel, Switzerland; www.roche.com). Insulin samples were measured with an enzymelinked immunosorbent assay kit.

In the study, prediabetes was classed as an fasting glucose (FG) level of 110125 mg/dL (6.1-6.9 mmol/L) and/or a HbA1c level of 6%–6.4%. The presence of prediabetes among study participants was assessed at study baseline, and subjects were followed-up for a median of 5.6 years. At study baseline, 595 of the participants had prediabetes. After adjusting for participants’ lifestyle and use of medications, the scientists found those with prediabetes had a higher measured GFR (mGFR) during follow-up than those without prediabetes, which is a sign of hyperfiltration in the kidneys. The team also found that high FG levels at baseline among these subjects were associated with high levels of the protein albumin in the urine during follow-up, an early sign of kidney disease.

Toralf Melsom, MD, PhD, the lead author of the

study said, “Our study shows that the pathological process of kidney injury caused by elevated blood glucose levels starts in prediabetes, well before the onset of diabetes. Prediabetes may be a target for early intervention to prevent chronic kidney disease (CKD) caused by hyperglycemia. If a patient has borderline elevated glucose levels found by their primary physician they should start lifestyle changes with respect to diet and physical activity to preventing diseases like diabetes and kidney disease.” The study was published on December 29, 2015, in the American Journal of Kidney Disease.

Image: The fully automated VARIANTII hemoglobin testing system (Photo courtesy of Bio-Rad Laboratories).

De Novo Mutation Causes Fanconi Anemia anconi anemia is clinically typified by susceptibility to bone marrow failure, leukemia, different types of solid tumors, and a strongly reduced life expectancy of the affected persons. Fanconi anemia (FA) is a rare recessive genetically heterogeneous chromosomal instability disorder with both autoso-

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mal and X-linked inheritance and all reported cases so far have displayed a recessive mode of inheritance. FA is characterized by multiple congenital abnormalities, hematological defects and a high predisposition to a diversity of cancers, including childhood acute myeloid leukemia and head and neck cancers.

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An international team of scientists led by those at the Institute for Systems Biology (Seattle, WA, USA; www.systemsbiology.org) used advanced whole genome sequencing as well as other cell and molecular biology techniques. Genomic DNA was isolated from lymphoblastoid cell lines of the patient, the healthy sibling and the parents and whole genomic sequencing performed. Mutation confirmation by Sanger sequencing was done by direct sequencing of polymerase chain reaction (PCR) products.

Samples were analyzed with an ABI 3730 DNA analyzer (Applied Biosystems; Foster City, CA, USA; www.appliedbiosystems.com). Other techniques used included cell cultures and transformations, growth inhibition analysis, cell viability assays, protein analysis, protein expression and purification, and cell cycle analysis which were performed subsequently by flow cytometry using a Particle Analyzing System (PAS, Partec; Görlitz, Germany; www.sysmex-partec.com).

D-loop formation, ATPase, DNA-binding assays were also carried out. Scanning force microscopy images were obtained on a NanoScope IIIa (Digital Instruments; Santa Barbara, CA, USA;

www.veeco.com).

The scientists found a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in one allele of the homologous recombination DNA repair gene RAD51 in an FA-like patient. This heterozygous mutation causes a novel FA subtype, “FA-R,” which appears to be the first subtype of FA caused by a dominantnegative mutation. The patient, who features microcephaly and mental retardation, has reached adulthood without the typical bone marrow failure and pediatric cancers.

Patrick May, PhD, a coauthor of the study, said, “The particular mutation in this patient was a surprise to us. It occurred only in one of the two RAD51 gene copies, which every person carries in the genome, but every RAD51 gene copy was normal in the child´s parents. In consequence the protein with the altered amino acid sequence due to the mutation interfered with the activity of the normal protein. These are the reasons why the child is affected by Fanconi Anemia although his or her relatives are not carrier of the mutation.” The study was published on December 18, 2015, in the journal Nature Communications.

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New Infectious Disease Test Promises Quick Diagnosis arly detection of specific pathogens has long been recognized as a vital strategy in the control of infectious diseases because it can lead to timely care of patients and prevent potential outbreaks.

The detection of specific bacteria represents a significant challenge because of the presence of many different species of bacteria in biological samples. Furthermore, for any given species of bacterium, only virulent strains are infectious while other strains of the same species may be harmless or even beneficial to human health.

A team of scientists led by those at McMaster University (Hamilton, ON, Canada; www.mcmaster.ca) found a way to make DNAzymes, or singlestranded catalytic DNA molecules from a simple test tube technique that allows for isolation of rare DNA sequences with special functions.

The team’s first success was the development of a molecular probe that

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precisely recognizes the strain, which caused the outbreak of Clostridium difficile infection in Hamilton, Ontario in 2011. This strain was very infectious, resistant to antibiotics and even fatal to some patients. Instead of having to do several different tests to narrow down to a positive identification of the specific strain, the scientists can now quickly pinpoint this superbug using their new molecular probe.

The team obtained an RNA-cleaving fluorogenic DNAzyme (RFD) that can recognize an infectious strain of C. difficile. This DNAzyme not only exhibits no cross-reactivity to other bacterial species, but also is highly strain-selective for C. difficile. The special DNAzyme (catalytic DNA), RFD-CD1, showed exquisite specificity for a pathogenic strain of C. difficile. RFD-CD1 was derived by an in vitro selection approach where a random-sequence DNA library was allowed to react with an unpurified molecular mixture derived from this

strain of C. difficile, coupled with a subtractive selection strategy to eliminate cross-reactivities to unintended C. difficile strains and other bacteria species.

Bruno J. Salena, MD, an associate professor of medicine and coauthor of the study, said, “This technology can be extended to the further discovery of other superbug strain-specific pathogens. For example, such technology would prove useful in the identifi-

cation of hypervirulent or resistant strains, implementation of the most appropriate strain-specific treatments and tracking of outbreaks.” The study was published on December 16, 2015, in the journal Angewandte Chemie International Edition.

Image: A colored transmission electron micrograph (TEM) of Clostridium difficile forming an endospore (red) (Photo courtesy of Dr. J. Thomas Lamont).

Rapid Test Accurately Profiles Brain Tumor Genetics rain tumors can be rapidly and accurately profiled with a next-generation, genesequencing test recently developed. The test, called GlioSeq, is now being used by oncologists to help guide treatment planning of brain cancers.

Historically, the diagnosis of central nervous system (CNS) tumors has been based primarily on histopathologic features. However, patients with morphologically identical tumors may experience different clinical outcomes and responses to treatment because the underlying genetic characteristics of the tumors differ.

Scientists at the University of Pittsburgh Schools of the Health Sciences (PA, USA; www. upmc.edu) and their colleagues used GlioSeq, a next-generation, gene-sequencing assay, to test 54 adult and pediatric brain tumor samples for genetic abnormalities, including point mutations, gene fusions, and small gene insertions and deletions that had already been characterized by other means. They used next-generation sequencing to simultaneously identify all previously known alterations, as well as many additional genetic markers in these tumors. This provided important information on classification of these tumors, and on possible new targets for therapy.

The teams identified 30 genes with genetic alterations repeatedly found in CNS tumors and designed custom DNA primer pools to generate libraries and sequence more than 1,360 CNS tumor-related hot spots of more than13,000 all cancer hot spots). The GlioSeq performance was evaluated in 54 CNS tumor specimens collected in 2012–2015, including 28 formalin-fixed, paraffin-

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embedded (FFPE) and 26 snap-frozen tissues. The investigators compared the GlioSeq cost of reagents with the cost of reagents using conventional techniques such as Sanger sequencing, reverse transcription polymerase chain reaction (RTPCR), and single nucleotide polymorphism array, that are needed to detect all types of genetic alterations and determined that conventional methods would cost 15 times more than GlioSeq analysis.

Frank S. Lieberman, MD, a professor of neurology, neurosurgery and medical oncology and

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co-author of the study said, “This test can help guide the physician and the patient in planning treatment, since the molecular information allows us to more precisely characterize tumors and more confidently predict survival and response to therapy. In addition, Glioseq facilitates the identification of clinical trial options with the appropriate molecular targets, as well as cases in which molecularly targeted drugs are available.”

The study was published on December 17, 2015, in the journal Neuro-Oncology.

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Blood Culture Detection Times Distinguishes Bacteremia from Contamination ontamination of blood culture is common, very costly for the health system, and often confuses clinicians. To minimize the risk of blood culture contamination with the normal skin flora, meticulous attention should be paid when preparing the skin for venipuncture.

Clinicians should be notified every time there is a positive blood culture because the microorganism can often represent an infection that may lead to death and moreover, knowledge of the start times for adequate antibiotic therapy is critical for the prognosis of patients with sepsis and bacteremia.

Scientists at the Fuenlabrada University Hospital (Madrid, Spain; www.uam.es) conducted a retrospective study of a database of 1,334 patients with a positive blood culture between January 2011 and June 2013. Together with the final blood culture results and the patient’s history, growth was then analyzed to assess whether it represented true bacteremia or bacterial contamination. The earliest detection times of bacterial growth in each batch of blood cultures were analyzed in a blinded fashion after classification. The BacT/Alert blood culture system (BioMérieux; Marcy l’Etoile, France; www. biomerieux-diagnostics.com) was employed

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throughout the study. Two pairs of blood culture vials were used for each patient, with a total recommended extracted volume of blood of 20 mL to 40 mL. These four vials, two for aerobic and two for anaerobic culture, were termed a “blood culture batch.” Blood cultures were performed depending on medical criteria in patients with suspected sepsis as there is no predictive model able to identify which patients should have blood cultures done.

In total, 590 batches of blood cultures corresponded to true bacteremia and 744 to bacterial contamination. In the bacteremia group, the median growth time was 12.72 hours. In the contaminated blood culture group, the median growth time was 20.6 hours which was statistically highly significant. Microorganisms such as Candida species and Bacteroides species presented median growth times significantly longer than those of the other microorganisms. The administration of antibiotics in the week prior to bacteremia was found to delay the growth time of microorganisms.

The authors concluded that the time at which growth is detected in blood cultures using the automated BacT/Alert system could inform clinicians of whether the culture represents true bacteremia or

not, pending the time required for a definitive identification of the microorganism involved. The factors that influence these growth times are the association of the culture with true bacteremia, the prior use of antibiotic therapy, and the type of microorganism. The study was published in the December 2015 issue of the International Journal of Infectious Diseases.

Image: The BacT/Alert blood culture system (Photo courtesy of BioMérieux).

Tumor Sample Purity May Significantly Bias Genomic Analyses he proportion of normal cells, especially immune cells, intermixed with cancerous cells in a given tissue sample may significantly skew the results of genetic analyses and other tests performed by physicians selecting precision therapies. Measures used to predict the effectiveness of checkpoint-inhibitor drugs, the most widely used form of cancer immunotherapy, are accurate only when the extent of infiltration of immune cells into the tumor was explicitly quantified. When this aspect of tumor purity was not accounted for, estimates of the likely success of immunotherapy were either too high or too low.

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Scientists at the University of California, San Francisco (CA, USA; www.ucsf.edu) made use of a massive dataset known as The Cancer Genome Atlas (TCGA), a joint initiative of the National Cancer Institute and the National Human Genome Research Institute. The TCGA dataset is derived from samples of tumors and normal tissue from 11,000 patients, and represents 33 types of cancer. The team used four different methods to measure tumor purity in more than 10,000 TCGA samples representing 21 cancer types, and examined how purity might affect the reliability of three of the most common genomic methods used in cancer research:

correlation, clustering, and differential analysis.

In a type of bladder cancer known as bladder carcinoma, for example, two genes called Janus Kinase 3 (JAK3) and Colony Stimulating Factor 1 Receptor (CSF1R) tend to be jointly expressed at high levels, which suggests that they somehow act together to drive the cancer. The team found that the tandem expression of JAK3 and CSF1R in bladder carcinoma varied widely if tumor purity was taken into account as in the purest samples there was little correlation between the expression of the two genes, calling their potential joint role in a cancerdriving pathway into question.

Urine Test Helps Diagnose Bladder Cancer ladder cancer is the seventh most common type in the UK, with around 10,000 people diagnosed every year and around two-thirds of cases recur within five years, so patients are monitored routinely after treatment.

Patients with bladder cancer are currently tested and monitored via an invasive cystoscopy examination, which involves passing a thin device through the urethra, the tube which carries urine out of the body, to examine the inside of the bladder.

Clinicians at Southampton General Hospital (UK; www.uhs.nhs.uk) are set to lead a pioneering UK study into the use of a urine test that could help to diagnose bladder cancer. The team will recruit around 40 patients

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who have been diagnosed with the disease to participate in the trial.

They will take urine samples from patients before treatment begins and at every follow-up appointment over a six-month period.

The test works by detecting a protein known as minichromosome maintenance complex component 5 (MCM5), which is shed into urine by bladder and prostate tumors. The MCM5- enzyme-linked immunosorbent assay (ELISA) was developed by Arquer Diagnostics Ltd. (Sunderland, UK; www.arquerdx.com). A recent successful screening trial involving 350 hematuria patients indicated that the MCM5-ELISA test has a sensitivity of 83%, a specificity of 77% and negative predictive value of 98%.

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Edited by Tahir Pillay MBChB, PhD, FRCPath(Lon), FCPath(SA) IFCC members may send news to: Tahir Pillay MBChB, PhD, Head, Dept of Chemical Pathology, Faculty of Health Sciences, University of Pretoria, Private Bag Bag x323, Arcadia, 0007, South Africa Tel: (27) 12 319-2116; Fax: (27) 328 6000; Email: enews@ifcc.org

NEWS

Three Candidates to Compete in Election of Next IFCC President

by Dr Bernard GOUGET, chair, IFCC Nominations Committee he IFCC-NC received three nominations for IFCC PresidentElect position. The President elect will start on January 1st, 2017 to be confirmed as IFCC President on January 1st, 2018 until 31st December 2020. The 3 candidates have been nominated by their National Societies which are in good standing.

The candidates have given a written consent for their candidacy. All applications were declared valid and all three will go into the ballot. The candidate are: Prof. Howard Morris (Australasian Association of Clinical Biochemists; AACB); Prof. Tomris Özben (Turkish Biochemical Society; TBS); Prof. Tomáš Zima (Czech Society of Clinical Biochemistry; CSKB).

Full details of each candidate’s nomination including a personal statement are available at following link: www. ifcc.org/media/417125/IFCC_EB_ 2017_2020_President_elect_slate_of_ candidates.pdf All IFCC Officers’ elections take place electronically; accordingly, the electronic ballot for the election of the President-elect position, will be held during September 1-30, 2016. The voting body will consist of IFCC full member societies.

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Prof. Howard Morris Australia

IFCC Institutes Medal For Outstanding Service

By Maurizio Ferrari, IFCC President Introduction: The IFCC Executive Board has agreed to introduce the IFCC Medal for Outstanding Service (hereinafter ‘The Medal’) in recognition of sustained service to IFCC by an individual at the highest level in promoting the international practice of clinical chemistry and laboratory medicine. The first award of The Medal will be made in 2017 and nominations are now being sought with a closing date of 31st December 2016.

Eligibility: Individuals who are eligible to receive The Medal will be members of an IFCC Full or Affiliate Member Society or an IFCC Corporate Member Company. To be eligible individuals will have worked in a voluntary capacity at a global or multi-national level over a period of at least ten years during which they will have served in a voluntary capacity for IFCC for a minimum of six years.

Eligible individuals will have made an exceptional contribution to promoting the practice of clinical chemistry and laboratory medicine.

Serving Members of the IFCC Executive Board are not eligible for nomination.

VISIT US AT:

2016

ANNUAL MEETING

Booth: 2349

Nomination Process: Nominations for The Medal should be submitted by the IFCC cont’d on page 62

IFCC OFFICE Via Carlo Farini 81, 20159 Milan, ITALY Tel: (39) 02-6680-9912 • Fax: (39) 02-6078-1846 E-mail: ifcc@ifcc.org • Web: www.ifcc.org Office Hours: 8.30-13.00 and 13.30-17.30 Staff Members: Paola Bramati, Silvia Cardinale, Silvia Colli-Lanzi

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Prof. Tomris Özben Turkey

Prof. Tomáš Zima Czech Republic

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

NEWS IN MEMORIAM

Prof. Daniel Mazziotta, EB Member (2015-2016)

By Rosa Isabel Sierra-Amor, IFCC EB Member. he IFCC community, both across Latin America and worldwide, deeply saddened by the death of Prof.

Daniel Mazziotta from Argentina.

Daniel passed away quietly in Buenos Aires on Sunday, February 14, 2016.

The IFCC has lost one of its brightest and sharpest specialists in lab medicine who contributed to worldwide IFCC reputation with a broad smile, spreading enthusiasm in promoting Lab Medicine well beyond the Latin American borders.

Daniel Mazziotta participated very actively in IFCC, beginning as corresponding member of the Committee on Analytical Quality (C-AQ) of the Education and Management Division (1992). After that, he was member of the Nomination Committee (1994) and full member and Chair of the CAQ (1997, 1998-2002). In 2002, he was elected Member of the IFCC Executive Board (2003-2005, 20062008), and elected again for the term 2015-2017. Unfortunately, he could not resist the cancer he suffered for several years already.

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Daniel was Professor of Clinical Chemistry at National University of La Plata as of 1989, Director of the External Quality Assessment Program of the Argentine Biochemical Foundation as of 1987 and Director of the Reference and Standardization Laboratory in Clinical Biochemistry of Argentine Biochemical Foundation (1997). He graduated in Chemistry (1974) and Biochemistry, Clinical Orientation (1976) at the National University of La Plata, Argentina. From 1974 to 1982, he served the Central Laboratory Service of the Hospital San Juan de Dios of La Plata working for the Intensive Care Unit and the Heart and Lung Functional Exploration Service. He became member of the Central Commission of External Quality Control of the Ministry of Health of Province of Buenos Aires (1978) and the organizer of External Quality Control Program for the same Ministry from 1980 to 1986.

He also participated very actively in other organizations, holding positions as member of the Executive Board of the Specialists on Biological Analyses

Association (1984 and 1986), Secretary of the Biochemical Federation of the Province of Buenos Aires (1986 to 1992). Member of the Permanent Scientific Section of the Latin-American Confederation of Clinical Biochemistry since 1987. In addition, he was also National Representative of Argentina.

He contributed as member of the Editorial Board of Acta Bioquimica Clinica Latinoamericana, the official journal of the Latin-American Confederation of Clinical Biochemistry (COLABIOCLI), and Member of the Intercontinental Board of Accreditation and Quality Assurance journal. He received the American Association for Clinical Chemistry International Fellowship Award in 2000. He was Honorary National Member of the Argentine Medical Association and Member of Honour of the Cuban Society of Clinical Pathology. In 2006 he received an award for his Professional Career in Argentina after developing intensive post-graduate education courses on Quality Control around the country, as well as in many Latin-

American countries, including Bolivia, Chile, Paraguay, Uruguay, Dominican Republic, Ecuador, Guatemala, Costa Rica, Honduras, Mexico, Venezuela and Brazil. He acted as advisor for the Pan-American Health Organization in Guatemala and Ecuador.

We express our appreciation to Daniel for his efforts promoting quality management and laboratory medicine worldwide.

Your friendship was of great value to all. Daniel, you will be missed with great respect!

IFCC Institutes Medal for Outstanding Service

contâ&#x20AC;&#x2122;d from page 61

Member to the IFCC Secretary by 31 December each year. Nominations should comprise: A letter of nomination on headed notepaper, which explains the outstanding international contribution made by the nominee A copy of the Curriculum Vitae of the nominee Nominations may be accompanied by at least three letters of support that illustrate how the nominee meets the eligibility criteria.

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Process: The Medal is awarded on the recommendation of the IFCC Executive Board and is ratified by the IFCC Council without appeal. The Medal is presented at an IFCC WorldLab congress, or an IFCC Regional Federation congress or the IFCC General Conference. There is no limit on the number of Medals presented but the eligibility criteria suggest that the number will be small. There is no requirement to award The Medal in any triennial period.

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Recognition: A short article will be published in IFCC News to recognise each recipient of The Medal. The names of recipients of The Medal will be listed in the IFCC Handbook and in the IFCC website The Medal: The Medal will comprise a medallion in a presentation box. The Medal will bear the IFCC logo, the name of the recipient and the year in which it was awarded. No honorarium is attached to the award.

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News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

NEWS

Tunisian Society Marks 35th Anniversary at Hammamet Congress

by Prof. Hmida SLAMA, STBC President, Prof. Farouk BARGUELLIL, STBC Vice-President and Dr Bernard GOUGET, chair, IFCC Nominations Committee, General Secretary FIFBCML he Société Tunisienne de Biologie Clinique (STBC) celebrated its 35th birthday at the 30th Journées Nationales de Biologie Clinique (30th Clinical Biology Conference, JNBC), that took place in Hammamet from May 12-14, 2016. More than 800 participants gathered in the presence of 11 countries of the Arab Federation of Clinical Biology (Dr. Mohammed Hassan KAMIL, AFCB President), the executive board members of the FIFBCML (Dr Marc-Antoine Zablith, Président), the Syndicat des Biologistes (FR) (Dr François Blanchecotte, President) and the Fédération EuroMediterranéenne des Laboratoires (Jean Benoit, FeMLab President, Dr Bari Cherif, General Secretary and Jean Begué).

The three-and-a-half decades of continuous activity of the STBC have provided support to Tunisian laboratory medicine specialists in their daily professional practice. This long-term commitment led to a mature operation, that allowed the STBC to undertake ambitious projects, especially to meet the challenges of restructuring laboratory medicine in Tunisia. Therefore, the STBC is strongly invested in developing continuing education and in the quality assurance and accreditation process according to standard ISO 15189.

The STBC is always available to national organizations to defend scientific expertise, specificity of practice and the interests of the profession within the medical profession and Tunisian healthcare facilities. It therefore plans to set up continuing professional development based on the French experience. The STBC is also active internationally with IFCC, AFBC, AFCC, and FIFBCML.

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LabMedica International June-July/2016

Laboratory medicine, benefiting from increasingly precise knowledge of cellular and molecular structures, encompasses both scientific and social issues. It stands out as a dynamic discipline that provides a great deal of hope in addressing the major health scourges. The 30th JNBC brought together international and Tunisian speakers. They began with the 3rd Arab course in molecular biology (PCR-RFLP) and two workshops: critical reading of scientific articles and a lesson on high-throughput DNA sequencing and its applications in clinical biology. The subjects included the role of laboratories in the performance of hemodialysis centers.

Prof. Christophe BURUCOA inaugurated the conferences with a discussion of microbiota. The other subjects related to heparins and biosimilars (Prof. Mehdi DRIDI), endocrine disruption (Prof. Jacques AUGER), fetal DNA in maternal circulation (Prof. Annie LEVY), computerization of medical biology laboratories and standard ISO 15189 (Alain COEUR).

The other sessions brought us upto-date on: molecular biology in diagnosis and follow-up of hematological malignancies, chronic inflammatory bowel disease (IBD), toxoplasmosis, autoimmunity, LC/MS and its applications in clinical biology and infection with multidrug-resistant bacteria (MDROs).

Thanks again to the many industrial partners who held satellite workshops on the sidelines of the exhibition on early detection of colon cancer and prenatal screening for trisomy 21 and preeclampsia.

E-posters have attracted many young people to discuss their work and for some of them to receive a prize.

Today, by celebrating its thirtieth birthday, the STBC showed that it is capable of a great deal of energy and determination to bring the Tunisian and foreign medical biologist communities together and that Tunisia is more than ever a land of welcome, openness and tolerance that offers foreigners a strong tradition of hospitality and openness.

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NEWS

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

Mexico City Symposium Focuses On Alzheimer’s Biomarkers

By Rosa Sierra Amor, IFCC Executive Board Member; Sergio Bernardini, IFCC Executive Board Secretary exico City hosted the 2nd IFCC Symposium of Biomarkers of Alzheimer Disease (AD), at the Hotel Camino Real Polanco on May 20th, 2016. It was a high-level conference with more than 70 attendees and an excellent scientific programme.

During the Symposium, the speakers focused on the following issues:

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The bad news: “We are waiting for a big wave of AD all over the world. That’s for sure! Currently we don’t have reliable blood tests for screening, no prevention programmes, no an effective cure” (Ralph Martins).

“The Neuropathology is very complicated. It is not a WES or NO as in other diseases (cancer) but HOW MUCH is that?. Very often the different kind of histological aggregates (Ab, a synuclein, TDP-43, CVD) are superimposed, almost nothing seemed to be pure..” (Johannes Attems).

“Impressive has been the analysis of preanalytical confounders, there is a huge preanalitical and analytical variability as well as variability in cut off values”. (Armand Perret Liaudet).

“In many countries the laboPhoto: Speakers of the 2nd IFCC Symposium on Biomarkers of Alzheimer´s ratory diagnosis of neurode- Disease, held in Mexico City on May 20th, 2016. generative diseases cannot be set up because of financial constraints and para- a supportive treatments” (Ralph Martins).

“Ab1-42, tau and P-tau are robust biomarkers for doxically in these countries the prevalence is higher” diagnosis and progression and start to be patholog(Maria-Esther Jimenez-Capdeville). icaly positive 15 years before the onset of symptoms” (Kaj Blenow).

The good news: “Neuroimaging (with PET tracers) and laboratory “Lifestyle factors, and in particular phisical exercise and MeDi can influence a bit the outcome. Hor- analyses start to be integrated between them and monal environment and in particular testosterone, with clinical data as in the IWG2 Criteria. And this oestrogens and insulin resistance can be targets of will be really important to stratify patients in clinical trials. Moreover tau tracers will be available soon” (Leslie Shaw).

“Advancements in Genomic Medicine are ongoing and possibly will be able to intercept candidates for AD. Technological improvements are available as Next Generations Sequencers make it possible to study quickly APP1, Presenilins for EOAD and many minor candidate genes for LOAD as ApoE4, and other candidates such as clusterin, ABCA7, REM2, PLD3, MAPT, Progranulin, C9orf72 as well as immunoresponse and endocytosis proteins coding genes” (Maurizio Ferrari).

“Even targeted proteomics of CSF seems to be promising and many studies are ongoing less invasive matrices” (Sergio Bernardini).

“New diagnostic approaches are coming as the Retinal amyloid Fluorescent Imaging” (Ralph Martins) and “pathological Tau in the epidermidis” (Maria-Esther Jimenez-Capdeville).

“AD Association QC programs, reference measurement procedures and Reference certified material are available, or will be coming soon, limiting the fonts of variability” (Kej Blennow).

“New biomarker: the synaptic protein neurogranin is discovered and seems to be promising” (Kaj Blennow).

“A Prion-like, but not infectious way of propagation can be theorized and this can be another way to interfere with the progression” (Johannes Attems).

“Fully automated analytical systems are available” (Richard Batrlab) and “probably Mass Spectrometry becoming more popular and might become an important analytical support to diagnosis” (Kaj Blenow).

In summary, we could say that probably we are on the right path but we need to talk more and more about “dementia” disorders and strongly support research and educational programmes all around the world. We need to become aware of an actual health problem identifying AD patients properly, as well as other pathologies related to dementia.

Rosa Sierra-Amor and Sergio Bernardini, IFCC EB Member and Secretary respectively coordinated this activity. Thanks to Roche Global for their support in organizing it, and to the speakers for making it possible to learn and hear the latest news about the importance of Biomarkers of Alzheimer´s Disease.

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News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

NEWS

IFCC Welcomes Nepalese National Society As New Affiliate Member

by Ram Vinod Mahato General Secretary Nepalese Association for Clinical Chemistry (NACC) epalese Association for Clinical Chemistry (NACC) is a non-governmental and non-profit organization that currently organizes more than two hundred Nepalese biochemists/clinical chemists who are engaged in the field of laboratory medicine, healthcare set-ups, academics and research. After a yearlong effort, NACC was officially born on 4th July 2014, when it was formally registered by the government. NACC has its headquarters in the capital, Kathmandu. It has several of the most senior and experienced biochemists of Nepal in its executive body. This is the only professional organization representing Nepalese professionals in biochemistry/clinical chemistry and laboratory Medicine. Hence, it has the sole responsibility of safeguarding professional rights, promoting improvement and expansion of the quality services in laboratory medicine and opening new avenues for research and collaborations for professional and academic growth. NACC believes that these goals for upholding the profession of biochemistry/clinical chemistry can be fulfilled only by meeting the following specific objectives to: 1. Increase awareness of the importance of clinical chemistry in the lay community and assist them in getting quality laboratory services.

2. Organize and operate assemblies, conferences, meetings, symposiums and CMEs. 3. Gather and award research grants to any member of this Association who proposes high quality research work with specific relevance to Nepal within the subject area of the association.

4. Promote collaborative research activities nationally and internationally.

5. Provide grants for thesis/dissertation to co-members of this Association who present appropriate proposals for their thesis/dissertation.

6. Submit opinions, suggestions and information to the governmental, non-governmental bodies and universities concerned related to clinical chemistry, chemicals/reagents and procedures by evaluating their worth.

7. Grant honorary membership to any person who makes remarkable contribution for development and promotion of the clinical biochemistry subject both inside and outside Nepal.

8. Monitor and deliver opinions and suggestions for assessment of quality of the clinical biochemistry laboratory and after prior approval from the departments concerned run External Quality Assessment (EQAS and IQC) and Good Laboratory Practice (GLP) programmes.

9. Coordinate with the relevant departments the necessity for development of curriculum, examination system and valuation, function and duties of designated professionals and their assessment.

10. Organize suitable training events for refining skills and knowledge of clinical chemists and issue certificates upon completion.

11. Publish news bulletins and journal including news.

12. Coordinate with national and international organizations such as IFCC, AACC, APFCB, AACB, ACBI, etc., and to organize Invited lectures from foreign scholars.

13. Represent the association in the programmes of the national and international organization of a similar nature.

14. Implement the aforementioned objectives by applying to local administration for a license and obtaining it, whenever relevant.

Executive Board Members: President: Prof. Bharat Jha-Tribhuvan, University, Institute of Medicine (IOM),

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Kathmandu; Sr. Vice-President: Prof.Dr. Madhab Lamsal, BP Koirala Institute of Health Science, Dharan; Vice-President: Dr. Vijay Kumar Sharma, Tribhuvan University, Institute of Medicine (IOM), Kathmandu; Vice-President: Dr. Prabodh Risal, Kathmandu University Medical School (KUMS), Dhulikhel; General Secretary: Ram Vinod Mahato, Tribhuvan University, Institute of Medicine (IOM), Kathmandu; Secretary: Dr.Suprita Gupta, National Medical College and Hospital, Birgunj; Treasurer: Mr. Prasant Regmi, Nepal Medical College (NMC), Kathmandu.

Some highlights of the current and past activities of NACC: 1. Organization of National Symposium of Clinical Biochemistry and Laboratory Medicine on March 13-14, 2015.

2. Publication of Annals of Clinical Chemistry and Laboratory Medicine, an official Journal of NACC: http://nacc.org.np/submit-a-manuscript or www. nepjol.info/index.php/ACCLM/user/register. Author guidelines can be found at www.nepjol.info/ index.php/ACCLM/about/submissions#author Guidelines 3. Received membership of Asia Pacific Federation for Clinical Biochemistry (APFCB) and International Federation for Clinical Chemistry (IFCC).

The associationâ&#x20AC;&#x2122;s official web page (www. nacc.org.np) contains the latest news and information. E-mail: nacc2070@gmail.com.

EFLM CORNER Editor: Harjit Pal Bhattoa, MD, PhD, EuSpLM

European Federation of Clinical Chemistry and Laboratory Medicine

12th EFLM Balkan Symposium Held in Conjuction with 20th Serbian National Congress

by Dr. Snežana Jovičić; Society of Medical Biochemists of Serbia n May 25–27, Society of Medical Biochemists of Serbia (SMBS) and Faculty of Pharmacy of the University of Belgrade organized the 20th Congress of Medical Biochemistry and Laboratory Medicine with international participation. The congress was organized under the auspices of International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), Balkan Clinical Laboratory Federation (BCLF), Ministry of Education, Science, and Technological Development, and Ministry of Health of Republic of Serbia. It had five sessions dedicated to the current findings in different areas of clinical chemistry and laboratory medicine, and their application in patient care.

During the opening ceremony, after the review of the past congresses through photos presentation, the traditional reward of the “Magistra Milica Marković” Foundation, intended to laboratories that advanced the most in the past two years between the two congresses, was awarded to the laboratory of the Community Health Centre “Palilula” from Belgrade. The reward was Alifax Test 1 BCL fully automated analyzer for determination of erythrocytes sedimentation rate, donated by the company Promedia. Also, on the occasion of the jubilee of the 20th Congress, SMBS delivered Diplomas and Acknowledgments to individuals and organizations that contributed significantly to the work of the SMBS and to the development of medical biochemistry in Serbia.

The working part of the 20th Congress officially started with the opening plenary lecture entitled “Quality assurance in clinical chemistry: a touch of statistics and a lot of common sense” held by the distinguished professor Elvar Theodorsson, from the Linköping University, Sweden. The first session was dedicated to the new biomarkers in laboratory medicine – the role of genome-wide association studies in new biomarkers discovery in the case of osteoporosis, paraoxonase enzymes in cardiovascular disease, LC-MS/MS for analysis of cholesterol synthesis and absorption markers, and adiponectin in coronary artery disease.

Toxicological, pharmacokinetic, and biochemical aspects of the application of drugs were the topics of the second session. The talks comprehended the influence of environmental pollutants cadmium and polychlorinat-

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ed biphenyls on thyroid hormone levels, the recommendations on application of therapeutic drug monitoring, diagnostic and therapeutic possibilities in familiar hypercholesterolemia, and Photo: Prof. Dr. Elvar Theodorsson with members of the Scientific and monitoring of biochemical parameters the Organizing Committee of the 20th Congress (from left to right – in the assessment of immunosuppres- Prof. Dr. Nada Majkić-Singh, Prof. Dr. Elvar Theodorsson, Dr. Zorica sive therapy safety. Šumarac, Dr. Snežana Jovičić, Dr. Velibor Canić).

The third session was dedicated to ple interferents testing, management of processes in contemporary methodological approaches in laboratory the preanalytical phase, the impact of laboratory test remedicine – application of HPLC-MS/MS techniques, sults, management of critical-risk results as a tool for PCR methodology implementation in pathogen detecimprovement clinicians' decisions, urinanalysis, critical tion and human genomics, implementation of the recomvalues reporting, solutions in monitoring performance in mendations of the World Health Organization in stanpre-pre and post-post analytical phases, managing labdardization of procedures for spermogram making, and oratory demand, clinical awareness about pre and post pharmacogenetics testing, biochemical and therapeutic analytical phase, and the level of communication bemonitoring as the basis of personalized medicine. tween clinicians and medical laboratory. Next to prof.

The fourth session elaborated the role of oxidative Plebani, the participants had the pleasure to hear about stress in contemporary diseases, as risk factor for the these issues from the eminent lecturers, members of development of eye disease, in prediabetes, then the EFLM and IFCC working groups – Prof. Dr. Gustav Korole of genetic polymorphisms of glutathione transferasvac, Dr. Zorica Šumarac, Prof. Dr. Ana-Maria Šimundić, es omega class in end-stage renal disease, and the role Dr. Laura Sciacovelli, Prof. Dr. Tatjana Cvetković, Prof. of reduced antioxidant defense and obesity in the develDr. Dunja Rogić, Prof. Dr. Éva Ajzner, Prof. Dr. Svetlana opment of cardiovascular disease in young people.

Ignjatović, Prof. Dr. Mercèdes Ibarz, Dr. Pinar Eker, and The closing, fifth session was dedicated to molecuAssoc. Prof. Dr. Snežana Jovičić; as well as from nalar biomarkers of diagnosis and monitoring of therational specialists in this field – Assoc. Prof. Dr. Neda peutic response in immune diseases – multiple scleroMilinković, Dr. Vera Lukić, Dr. Drina Topalov, Dr. Biljana sis, liver fibrosis and celiac disease.

Glišić, and Dr. Zorica Reljić.

As part of the 20th Congress, the 12th EFLM SymThe congress program also included two industriposium for Balkan Region was organized by the SMBS al workshops and poster session, with notable particand EFLM on May 26 and 27. This year’s Symposium ipation of students of medical biochemistry at the Facwas entitled “Harmonization of the total process: Influulty of Pharmacy, University of Belgrade, with their reence of the extra-laboratory phases”. The Symposium search results. was opened with the plenary lecture by the distinThe 20th Congress and 12th EFLM Symposium guished Prof. Mario Plebani, the leading expert in this for Balkan region were marked with significant attenfield, entitled “Extra-analytical phases quality managedance of medical biochemists and laboratory specialment: New achievement”. ists from mostly Serbia, but also from Bosnia and During the four-part program, European and SerHerzegovina, Montenegro, Croatia, Macedonia, and bian lecturers presented different aspects of important Turkey. With the closing of these events, SMBS has issues in extra-laboratory phases. The topics covered announced the 13th EFLM Symposium for Balkan rational ordering of laboratory parameters, harmonizaRegion for September 2017, which will be dedicated tion and external quality assessment of preanalytical to laboratory medicine management and leadership phase, quality indicators, application of biological variskills for effective laboratory. ability, drug interferences, systematic automated sam-

Hong Kong’s Prof. Dennis Lo to Keynote 4th Joint EFLM-UEMS Congress in Warsaw he Scientific Committee of the 4th Joint EFLMUEMS Congress in Warsaw is proud to announce that key speaker at the Opening Ceremony on Wednesday September 21 will be Prof. Dennis Lo (Dept of Chemical Pathology, The Chinese University of Hong Kong) with the lecture “Plasma DNA: Driver of a revolution in molecular diagnostics for the clinic”.

Prof. Dennis Lo is the Director of the Li Ka Shing Institute of Health Sciences, Head of the Department of Chemical Pathology of the Chinese University of Hong Kong (CUHK) and the Associate Dean (Research) of the Faculty of Medicine of CUHK. He graduated from the University of Cambridge and obtained MD and PhD degrees from the University of Oxford.

He worked as a lecturer at the John Radcliffe Hospital, the teaching hospital of the University of Oxford Clinical School.

In 1997 he discovered the presence of fetal DNA in maternal plasma. His research team was the first to re-

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port the presence of cell-free fetal RNA and fetal epigenetic markers in maternal plasma and pioneered their as markers for noninvasive prenatal diagnosis.

Moreover, they demonstrated that cell-free fetal nucleic acids in maternal plasma could be used for the noninvasive prenatal diagnosis of fetal trisomy 21.

With the use of massively parallel sequencing and the development of novel bioinformatics strategies, Prof.

Dennis Lo created a genome-wide genetic map of the fetus based on the analysis of the small amounts of fragmented DNA found in the blood of pregnant women.

Prof. Dennis Lo has been the recipient of numerous awards, including the 2005 State Natural Science Award from the State Council of China, the 2006 IFCCAbbott Award for Outstanding Contribution to Molecular Diagnostics, the 2006 US National Academy of Clinical Biochemistry Distinguished Scientist Award, a Croucher Senior Medical Research Fellowship, the 2007 Sigi

Zeiring Award from the American Association of Clinical Chemistry and Fulbright Distinguished Scholar 2009. He was elected as a Fellow of the Royal Society in 2011 and as a Foreign Associate of the US National Academy of Sciences in 2013 Prof. Dennis Lo Do not miss the opportunity to attend the lecture of this eminent researcher and speaker talking about the future of the molecular diagnostic.

Visit the congress website at http://www.eflmuems.warsaw2016.eu/ to know more about the full scientific programme.

We look forward to seeing you in Warsaw this September!

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EFLM CORNER

European Federation of Clinical Chemistry and Laboratory Medicine

News from the Turkish Biomedical Society Turkey’s Woman Biochemists Raise Profile in EFLM and IFCC he Turkish Biochemical Society now has four new members in the various working groups of EFLM and IFCC. Prof. Dr. Yeşim Özarda was elected as the chair of IFCC Reference Intervals and Decision Limits Committee (C-RIDL). Following Prof. Dr. Sedef Yenice, chair of the IFCC Clinical Laboratory Management Committee (C-CLM), Prof. Özarda is Turkey’s second chair for one of the IFCC Committees. Prof.

Dr. Ferhan G. Sağın was elected as a member of the new IFCC Task Force on Geriatric Laboratory Medicine (TF-GLM). Mesude Falay MD was elected as a full member for EFLM Harmonisation of Total Testing Process Working Group and, last but not least, Merve Sibel Güngören MD is now a full member on EFLM Promotion and Publications Working Group (WG-P) in which she was previously a corresponding member.

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National Symposia in Kahramanmaraş and Adana pril and May 2016 were highly productive months with two national symposia on clinical chemistry.

The first symposium was held between April 7- 9, 2016 in the city of Kahramanmaraş, under the title The First Kahramanmaraş Thalasaemia Symposium. The symposium also included a one-day workshop entitled 'Hemoglobin Disorders'. The second forum was the Pre-Analytical Phase Symposium (Adana, May 19-20, 2016) starting with a half-day course of Biological Variation: Calculations and Applications. Additionally, another training course for phlebotomists was held within this symposium, the content of which was based on the Phlebotomy Guideline published by TBS in 2015.

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1st In Vitro Diagnostic Symposium Held in Izmir he 1st Turkish In Vitro Diagnostic (IVD) Symposium was held between 18-20 February 2016, in the city of Izmir on the Western coast of Turkey.

The symposium was organized under the cooperation of Turkish Biochemical Society, Izmir Branch and Dokuz Eylül University Health Sciences Institute. The special feature of this meeting was that IVD related topics were for the first time discussed in detail and with a multidisciplinary approach in Turkey. Lecturers and participants included: Academicians, medical laboratory supervisors, various specialists, scientists, representatives of Ministry of Health, Turkish Standards Institution as a conformity assessment body, representatives of leading manufacturers, researchers on health technology and biomedical engineering, students, and representatives from non-governmental organizations.

At the end of the symposium a final report covering designations, limitations and suggestions, was prepared in order to be presented to the national authorities and to be shared on the website of the symposium for the country's wider IVD community. The establishment of an online interactive IVD Medical Device portal related to the projected outcomes of the symposium was suggested in order to enable this issue to be dealt continuously and systematically, thus contributing to the dissemination of numerous activities in the field.

The various presentations, discussions, opinions and suggestions as part of this comprehensive and beneficial IVD symposium, contributed toward the development of strategies and policies for advancing R&D, production, quality standards, and innovation in Turkey's IVD medical device sector.

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Prof. Dr. Yeşim Özarda

Prof. Dr. Ferhan G. Sağın

Mesude Falay, M.D.

Merve Sibel Güngören, M.D.

EFLM CORNER

European Federation of Clinical Chemistry and Laboratory Medicine

58th National Conference in Szeged Celebrates 70th Anniversary of Hungarian Society t is our great pleasure to announce the 58th National Conference of the Hungarian Society of Laboratory Medicine (HSLM58), which will be held in Szeged, 25-27 August 2016. The conference is organised under the auspices of three main organisations of laboratory profession: the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), the International Federation of Clinical Chemistry (IFCC) and the European Union of Medical Specialists (UEMS). The Conference is the celebration of the 70th year anniversary of our Society (www.mldt.hu). A special issue of the electric Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (eJIFCC) has also been devoted to the 70-year-anniversary (www.ifcc.org/media/415280/ eJIFCC2016Vol27No2.pdf).

The conference, HSLM58 will be held at the Attila József Teaching and Conference Centre of the University of Szeged, which is Hungary’s first green conference centre in the heart of the city Szeged.

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The scientific program is planned in parallel sections including Case presentations in laboratory medicine, The role of laboratory medicine in clinical research, Routine laboratory diagnostics, Hematology and hemostasis, Endocrinology. A joint session of laboratory specialists with clinicians though real life clinical examples will focus on those steps of the total testing process, which should be shared responsibility of laboratories and clinicians.

A special plenary session (Youth forum – “You have the X FACTOR”) is organised for the novel research achievements of young laboratory scientists who will compete for the award of “The best young speaker of HSLM58”. In addition, separate sections are dedicated for plenary lectures of Lóránt Jendrassik prize - the greatest recognition of our Society awardees.

A distinguished attention will be paid to the daughter societies of HSLM as the Hungarian Society of Laboratory Professionals (MOLSZE) and the national

proficiency test provider QualiCont will be represented on HSLM58 with dedicated symposiums. We will celebrate that it was 20 years ago when HSLM cofounded both organisations.

E-poster sessions are also organised on HSLM58 when all posters will be presented in short oral presentations. E-poster sessions became very popular elements of HSLM congresses by now, since they induce live poster discussions and result in a better poster recognition.

In addition to the scientific content, social activities on HSLM58 will be also organised hoping that both scientific and social events of this conference will be unforgettable for you.

Organizing and Scientific Committees of HSLM58 as well as the Executive Board of HSLM invite you to celebrate the 70th year anniversary of our Society together! Szeged is waiting for you!

Imre Földesi, President of the HSLM58; Éva Ajzner, President of HSLM

Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) Promotes Residents’ Training he Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC), through its board of directors, promotes and gives new momentum to clinical laboratory specialists. To that end, the Society will increase the number of grants and double the amount granted, this year reaching €84,000.

Dr Imma Caballé, SEQC’s president, explains that the Society is committed to residents, their future and their training.

The SEQC “recognises how difficult it is to find a job once the residence has been

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completed and therefore we have decided to double the amount of grants and keep the residence period free of fees.”

Dr Caballé adds that “our goal is to facilitate and contribute to the improvement of continued training through diverse activities, including seminars, lectures through the web, pre-congress courses, Scientific Committee sessions, the edition of monographs and documents with experts’ recommendations, etc.”

Dr Dolors Balsells, a member of SEQC’s education committee and the secre-

tary of Fundación José Luis Castaño, emphasizes the need for constant training efforts to maintain professional competencies in the clinical lab speciality since “scientific advances in methodology and diagnostic proceedings, instrumental techniques, robotics or information systems require that specialists in this field update their knowledge constantly.”

To support residents’ and post-residents’ training in the different areas of clinical laboratory, SEQC – through Fundación José Luis Castaño – has launched this year seven post-residence grants, twice as many as in previous editions (financed, half by Fundación, and half by SEQC).

Also, SEQC subsidizes five grants to cover registration costs of all courses and meetings organised by SEQC and this year is offering four international grants for stages in labs in foreign countries where there is a scientific society subsidiary of IFCC (International Federation of Clinical Chemistry and Laboratory Medicine).

Through these actions and through the creation of a Residents’ committee within the scientific committee, the board of directors wants to reflect its concern for the future of residents and post-residents “since they will become the driving force of our Society a few years from now,” as Dr Balsells puts it.

Change of Guard at EFLM National Societies Ukrainian Society of Clinical Laboratory Diagnostics (USCLD) Dr. Dr. Valerii Dieiev, USCLD President, will also serve as EFLM National Representative replacing Dr. Igor Mishunin. A warm thanks to Dr. Mishunin for his collaboration during the past eight years.

Swedish Society for Clinical Chemistry (SFKK) Dr. Maria Berggren-Söderlund (Div. of Clinical Chemistry and Pharmacology, Dept. of Laboratory Medicine, Lund University) has been elected as new SFKK President replacing Dr. Mattias Aldrimer. A warm welcome to Dr. Berggren-Söderlund!

CIRME to Mark 10th Anniversary At Milan Conference he Research Centre for Metrological Traceability in Laboratory Medicine (CIRME) is pleased to celebrate its 10th anniversary, with the organization of an International Scientific Meeting in Milan (Italy) on 17th-18th November 2016 under the auspices of JCTLM, IFCC and EFLM. During this event, an international faculty will summarize the work done by CIRME from its creation and report the progress so far achieved in the field of metrological traceability in Laboratory Medicine.

In this regard, some world-renowned speakers will be in attendance to present lectures on very interesting topics, such as updates on standardization programs of specific analytes, how to manage the issue of standardization of heterogenous measurands, how to derive robust biological variation data and obtain analytical performance specifications and, last but not least, discussing the metrological traceability as a tool for improving the definition of reference intervals and the quality control schemes.

It is now widely recognized that only through the knowledge and the correct application of all these crucial aspects, Laboratory Medicine will be able to meet its main objective, namely to provide useful information for contributing to the right clinical decision-making and to the optimal quality of health-care. The complete programme of the meeting is available at http://users.unimi.it/cirme/home/index.php. To make registration, please access the following link: http://ems.mzcongressi.com/start/1189/eng.

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Industry News

International Calendar

Sysmex and Siemens Extend Alliance in Hemostasis Testing ysmex Corporation (Kobe, Japan; www.sysmex.co.jp/en) and Siemens Healthcare Laboratory Diagnostics (NY, USA; http://usa.healthcare.siemens.com) have announced an extension to their long-standing partnership through at least 2020. The contract extension adds a minimum of 2 additional years to the global supply, distributorship, and sales and service agreement for hemostasis clinical testing products.

The partnership enables clinical laboratories around the world to continue to benefit from the large portfolio. The companies, which began collaborating over 20 years ago, also agreed to continue joint hemostasis product development activities that will streamline and optimize lab testing.

Siemens Healthcare and Sysmex provide products used to test for blood clotting disorders, preoperative bleeding risk management, and monitoring of patients on anticoagulant therapy medications. In the past few years alone, the companies have introduced several cutting-edge INNOVANCE reagents and multiple new platforms for various laboratory set-

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tings, including the recent worldwide launch of the Sysmex CS-2500 System, and the US launch of the Sysmex CS-5100 System with optional track-based automation. (The products are not commercially available in all countries. Due to regulatory reasons their future availability cannot be guaranteed.)

The relationship extension was celebrated in April 2016 at Siemens AG headquarters in Munich (Germany; www.siemens.com). “We are pleased to extend our longstanding partnership with Siemens Healthcare,” said Hisashi Ietsugu, Chairman and CEO, Sysmex Corporation, “With the aging population, hemostasis testing has become even more important. Our partnership provides our customers with the innovative technologies needed to manage the increase in testing volumes, while providing accurate results for improved patient care.”

“The continued collaboration and 20-year partnership between Siemens and Sysmex is rare in the rapidly changing world of diagnostics,” said Franz Walt, President, Siemens Healthcare Laboratory Diagnostics.

Luminex Acquisition to Forge Premier Molecular Testing Portfolio uminex Corporation (Austin, TX, USA; www.luminex corp.com) and Nanosphere, Inc. (Northbrook, IL, USA; www. nanosphere.us) have entered into a definitive agreement under which Luminex will acquire Nanosphere, a leader in molecular microbiology and diagnostics, in an all-cash transaction valued at approximately USD 77 million (USD 1.70 per share).

With its focus on the molecular microbiology segment, Nanosphere delivers proprietary diagnostic tools that enable rapid and accurate detection of respiratory, gastroenteric, and bloodstream infections.

Benefits of the transaction include an ideal strategic fit: Nanosphere's Verigene platform, broad menu, and strong presence in the molecular microbiology market with over 240 customers to complement Luminex's customer base. The combination will add a growing revenue stream and new platforms for growth. It amplifies Luminex's market leadership as Nanosphere's Verigene technology leads in the high-growth bloodstream

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infection segment and complements Luminex's current infectious disease portfolio. Following the acquisition, only Luminex will be able to offer customers automated molecular platforms for both syndromic and targeted molecular diagnostic testing (Verigene and ARIES).

The merger is expected to immediately accelerate total revenue growth (accretive to Luminex’s adjusted earnings by end of 2017), reflecting Nanosphere's high doubledigit revenue growth and the ability to leverage Luminex's global molecular diagnostic distribution.

"The acquisition of Nanosphere will significantly enhance Luminex's growth trajectory by expanding our product portfolio, delivering access to new markets, and strengthening our pipeline of future products to make us the partner of choice for all molecular labs," said Homi Shamir, president and CEO, Luminex, "The deal demonstrates prudent execution of our fourth strategic growth pillar – leveraging our financial strength to accelerate growth in our target markets."

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AUGUST 2016 FIME 2016 – Florida International Medical Exhibition. Aug 2-4; Miami, FL, USA; Web: www.fimeshow.com

SEPTEMBER 2016 34th International ISBT – International Society Blood Transfusion Congress. Sep 38; Dubai, UAE; Web: www.isbtweb.org Eurotox 2016 – 52nd Congress of the European Societies of Toxicology. Sep 4-7; Istanbul, Turkey; Web: www.eurotox2016.com 55th Annual ESPE Meeting – European Society of Paediatric Endocrinology. Sep 1012; Paris, France; Web: www.espe2016.org 19th Annual Meeting of the ESCV – European Congress of Virology. Sep 14-17; Lisbon, Portugal; Web: www.escv.org ASCP 2016 – American Society for Clinical Pathology. Sep 14-17; Mandalay Bay, Las Vegas; Web: www.ascp.org 26th International CPOCT Symposium.

Sep 21-24; Copenhagen, Denmark; Web: www.aacc.org 4th Joint EFLM-UEMS Congress Laboratory Medicine at the Clinical Interface.

Sep 21-24; Warsaw, Poland; Web: www. ifcc.org/ifcc-congresses-and-conferences 15th International Congress on Antiphospholipid Antibodies. Sep 21-24; Istanbul, Turkey; Web: www.isbtweb.org ESP 2016 – 28th European Congress of Pathology. Sep 25-30; Cologne, Germany; Web: www.esp-pathology.org 42nd Annual Meeting of the American Society for Histocompatibility and Immunogenetics (ASHI). Sep 26-30; St. Louis, MO, USA; Web: www.ashi-hla.org BSACI – British Society of Allergy & Clinical Immunology Annual Meeting. Sep 29Oct 1; Telford, UK; Web: www.bsaci.org

OCTOBER 2016 BCLF 2016 - 24th Meeting of Balkan Clinical Laboratory Federation. Oct 1-4; Tirana, Albania; Web: www.bclf.info 40th European Congress of Cytology. Oct 2-5; Liverpool, UK; Web: www.britishcytology. org.uk Analytica China. Oct 10-12; Shangai, China; Web: www.analyticachina.com/ ASHG 2015- The American Society of Human Genetics. Oct 18-22; Vancouver, Canada; Web: www.ashg.org

NOVEMBER 2016 Association for Molecular Pathology (AMP) Annual Meeting 2016. Nov 10-12; Charlotte, NC, USA; Web: www.amp.org MEDICA 2016. Nov 16-19; Dusseldorf, Germany; Web: www.medica.de WASPaLM 2016- 29th World Congress of Pathology. Nov 18-21; Las Vegas, NV, USA; Web: www.waspalm.org 14th Asia-Pacific Federation for Clinical Biochemistry and Laboratory Medicine Congress. Nov 26-29; Web: www. apfcbcongress2016.org WCTD 2016 - World Congress on Clinical Trials in Diabetes. Nov 30-Dec 1; Berlin, Germany; Web: www.wctd2016.com

JANUARY 2017 The British Fertility Society (BFS) Annual

Meeting. Jan 5-7; Edinburgh, UK; Web: http://fertilityconference.org CBRD 2017 - 4th Caribbean Biomedical Research Days. Jan 16-18; Gros Islet, Saint Lucia; Web: www.stress-and-behavior.com

FEBRUARY 2017 SLAS 2017 - Society of Laboratory Automation and Screening. Feb 4-8; Washington, DC, USA; Web: www.slas.org Labquality Days2017. Feb 9-10; Helsinki, Finland; Web: www.labquality.fi

MARCH 2017 Pittcon Conference and Expo 2017. Mar 59; Atlanta, GA, USA; Web: http://pittcon.org KIMES 2017. Mar 16-19; Seoul, Korea; Web: www.kimes.kr ARABLAB 2017. Mar 20-23; Dubai, UAE; Web: www.arablab.com MEDLAB Asia Pacific 2017. Mar 29-31; Singapore; Web: www.medlabasia.com

APRIL 2017 ENDO 2017 – Endocrine Society Annual Meeting. Apr 1-4; Orlando, FL, USA; Web: www.endocrine.org MEDICAL FAIR INDIA. Apr 6-8; New Delhi, India; Web: http://medicalfair-india.com ECCMID 2017. Apr 22-25; Vienna, Austria; Web: www.eccmid.org/eccmid_2017

MAY 2017 Biomarkers & Diagnostics World Congress 2017. May 2-4; Philadelphia, PA, USA; www.biomarkerworldcongress.com ISLH 2017 – International Society of Laboratory Hematology. May 4-6; Honolulu, HI, USA; Web: www.islh.org 19th European Congress of Endocrinology. May 20-23; Munich, Germany; Web: www.ese-hormones.org/meetings ESPID 2017- European Society for Paediatric Infectious Diseases. May 23-27; Madrid, Spain; Web: www.kenes.com/ espid_2017_lp ESHG 2017 - European Human Genetics Conference. May 27-30; Copenhagen, Denmark, Web: www.eshg.org

JUNE 2017 EuroMedLab 2017. June 11-15; Athens, Greece; Web: www.ifcc.org FOCIS 2017 - Federation of Clinical Immunology Societies. June 14-17; Boston, MA, USA; Web: www.focisnet.org 2017 BIO International Convention. June 19-22; San Diego, CA, USA; Web: http:// convention.bio.org

JULY 2017 FEMS 2017- 7th Cong. of European Microbiologists. July 9-13; Valencia, Spain; Web: www.fems-microbiology2017.kenes.com AACC 2017 – 69th Annual Meeting of American Association for Clinical Chemistry. July 30-Aug 3; San Diego, CA, USA; www.aacc.org

SEPTEMBER 2017 ESP 2017 - 29th European Congress of Pathology. Sep 2-6; Amsterdam, Netherlands; www.esp-congress.org

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