As public health laboratories expand their genomic sequencing and bioinformatics capacity for the surveillance of different pathogens, labs must carry out robust validation, training, and optimization of wet- and dry-lab procedures. Achieving these goals for algorithms, pipelines and instruments often requires that lower quality datasets be made available for analysis and comparison alongside those of higher quality. This range of data quality in reference sets can complicate the sharing of sub-optimal datasets that are vital for the community and for the reproducibility of assays. Sharing of useful, but sub-optimal datasets requires careful annotation and documentation of known issues to enable appropriate interpretation, avoid being mistaken for better quality information, and for these data (and their derivatives) to be easily identifiable in repositories. Unfortunately, there are currently no standardized attributes or mechanisms for tagging poor-quality datasets, or datasets generated for a specific purpose, to maximize their utility, searchability, accessibility and reuse. The Public Health Alliance for Genomic Epidemiology (PHA4GE) is an international community of scientists from public health, industry and academia focused on improving the reproducibility, interoperability, portability, and openness of public health bioinformatic software, skills, tools and data. To address the challenges of sharing lower quality datasets, PHA4GE has developed a set of standardized contextual data tags, namely fields and terms, that can be included in public repository submissions as a means of flagging pathogen sequence data with known quality issues, increasing their discoverability. The contextual data tags were developed through consultations with the community including input from the International Nucleotide Sequence Data Collaboration (INSDC), and have been standardized using ontologies - community-based resources for defining the tag properties and the relationships between them. The standardized tags are agnostic to the organism and the sequencing technique used and thus can be applied to data generated from any pathogen using an array of sequencing techniques. The tags can also be applied to synthetic (lab created) data. The list of standardized tags is maintained by PHA4GE and can be found at https://github.com/pha4ge/contextual_data_QC_tags. Definitions, ontology IDs, examples of use, as well as a JSON representation, are provided. The PHA4GE QC tags were tested, and are now implemented, by the FDA's GenomeTrakr laboratory network as part of its routine submission process for SARS-CoV-2 wastewater surveillance. We hope that these simple, standardized tags will help improve communication regarding quality control in public repositories, in addition to making datasets of variable quality more easily identifiable. Suggestions for additional tags can be submitted to PHA4GE via the New Term Request Form in the GitHub repository. By providing a mechanism for feedback and suggestions, we also expect that the tags will evolve with the needs of the community.

Vaccine effectiveness (VE) studies utilizing the test-negative design are typically conducted in clinical settings, rather than community populations, leading to bias in VE estimates against mild disease and limited information on VE in healthy young adults. In a community-based university population, we utilized data from a large SARS-CoV-2 testing program to estimate relative VE of COVID-19 mRNA vaccine primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection from September 2021 to July 2022. We used the test-negative design and logistic regression implemented via generalized estimating equations adjusted for age, calendar time, prior SARS-CoV-2 infection, and testing frequency (proxy for test-seeking behavior) to estimate relative VE. Analyses included 2,218 test-positive cases (59 % received monovalent booster dose) and 9,615 test-negative controls (62 %) from 9,066 individuals, with median age of 21 years, mostly students (71 %), White (56 %) or Asian (28 %), and with few comorbidities (3 %). More cases (23 %) than controls (6 %) had COVID-19-like illness. Estimated adjusted relative VE of primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection was 40 % (95 % CI: 33-47 %) during the overall analysis period and 46 % (39-52 %) during the period of Omicron circulation. Relative VE was greater for those without versus those with prior SARS-CoV-2 infection (41 %, 34-48 % versus 33 %, 9 %-52 %, P < 0.001). Relative VE was also greater in the six months after receiving a booster dose (41 %, 33-47 %) compared to more than six months (27 %, 8-42 %), but this difference was not statistically significant (P = 0.06). In this relatively young and healthy adult population, an mRNA monovalent booster dose provided increased protection against symptomatic SARS-CoV-2 infection, overall and with the Omicron variant. University testing programs may be utilized for estimating VE in healthy young adults, a population that is not well-represented by routine VE studies.

Newborn screening (NBS), a comprehensive system that includes testing, diagnosis, follow-up, treatment, education, and evaluation, was recently named one of the Top 10 Great Public Health Achievements by the Centers for Disease Control and Prevention (CDC).1 Each year, approximately 10,000 infants are identified with NBS conditions, which frequently go unnoticed at birth.2 NBS is administered by state public health programs across the country and provides for early identification of newborns with certain congenital, metabolic, endocrine, hematologic, and other genetic conditions. Early identification of these conditions in newborns facilitates timely interventions that result in significant decreases in morbidity, mortality, and disability.1 | | Screening begins by pricking a newborn's heel to get enough blood to fill a few circles on a filter paper card. The specimen, referred to as a dried blood spot, is collected by a health-care provider—typically at the birthing facility—during the first 24–48 hours of life. Some states are required to collect two specimens, in which case the second specimen is collected between seven and 15 days of life. The specimens are then sent to a state-designated NBS laboratory for analysis. When a test result is out of normal range, laboratory or follow-up personnel contact the birthing facility and the newborn's physician to ensure the child receives the appropriate diagnostic work-up and treatment. NBS goes beyond blood-spot screening to include point-of-care testing for hearing and, in some states, critical congenital heart disease. These tests are performed at the hospital shortly after birth, and the state NBS program performs follow-up testing. Although there is some variability in protocols among states, most NBS programs have similar components, including specimen collection, laboratory testing, follow-up, education of providers and the public, verification of a diagnosis, treatment, and ongoing program evaluation.3

In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.

Fast, efficient public health actions require well-organized and coordinated systems that can supply timely and accurate knowledge. Public databases of pathogen genomic data, such as the International Nucleotide Sequence Database Collaboration (INSDC), have become essential tools for efficient public health decisions. However, these international resources began primarily for academic purposes, rather than for surveillance or interventions. Now, queries need to access not only the whole genomes of multiple pathogens but also make connections using robust contextual metadata to identify issues of public health relevance. Databases that over time developed a patchwork of submission formats and requirements need to be consistently organized and coordinated internationally to allow effective searches.To help resolve these issues, we propose a common pathogen data structure called the Pathogen Data Object Model (DOM) that will formalize the minimum pieces of sequence data and contextual data necessary for general public health uses, while recognizing that submitters will likely withhold a wide range of non-public contextual data. Further, we propose contributors use the Pathogen DOM for all pathogen submissions (bacterial, viral, fungal, and parasites), which will simplify data submissions and provide a consistent and transparent data structure for downstream data analyses. We also highlight how improved submission tools can support the Pathogen DOM, offering users additional easy-to-use methods to ensure this structure is followed.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

Persons receiving maintenance dialysis are at increased risk for SARS-CoV-2 infection and its severe outcomes, including death. However, rates of SARS-CoV-2 infection and COVID-19-related deaths in this population are not well described. Since November 2020, CDC's National Healthcare Safety Network (NHSN) has collected weekly data monitoring incidence of SARS-CoV-2 infections (defined as a positive SARS-CoV-2 test result) and COVID-19-related deaths (defined as the death of a patient who had not fully recovered from a SARS-CoV-2 infection) among maintenance dialysis patients. This analysis used NHSN dialysis facility COVID-19 data reported during June 30, 2021-September 27, 2022, to describe rates of SARS-CoV-2 infection and COVID-19-related death among maintenance dialysis patients. The overall infection rate was 30.47 per 10,000 patient-weeks (39.64 among unvaccinated patients and 27.24 among patients who had completed a primary COVID-19 vaccination series). The overall death rate was 1.74 per 10,000 patient-weeks. Implementing recommended infection control measures in dialysis facilities and ensuring patients and staff members are up to date with recommended COVID-19 vaccination is critical to limiting COVID-19-associated morbidity and mortality.

BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.).

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019–2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019–2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019–2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets. © 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

BACKGROUND: The potential for work to be a risk factor for coronavirus disease 2019 (COVID-19) was recognized early in the pandemic based on the likelihood of work-related differences in exposures to COVID-19 in different occupations. Due to intense demands of the pandemic, implementation of recommendations to collect information on occupation in relation to COVID-19 has been uneven across the United States. The objective of this study was to investigate COVID-19 test positivity by occupation. METHODS: We analyzed data collected from September 8 to November 30, 2020, by the Delphi Group at Carnegie Mellon University USCOVID-19 Trends and Impact Survey, offered daily to a random sample of US-based Facebook users aged 18 years or older, who were invited via a banner in their news feed. Our focus was ever testing positive for COVID-19 in respondents working outside the home for pay in the past 4 weeks. RESULTS: The major occupational groups of"Production", "Building and grounds cleaning and maintenance,""Construction and extraction,""Healthcare support,"and "Food preparation and serving" had the five highest test positivity percentages (16.7%-14.4%). Highest detailed occupational categories (28.6%-19.1%) were "Massage therapist,""Food processing worker,""Bailiff, correctional officer, or jailer,""Funeral service worker,""First-line supervisor of production and operating workers,"and "Nursing assistant or psychiatric aide."Differences in test positivity by occupation remained after adjustment for age, gender, and pre-existing medical conditions. CONCLUSION: Information on differences in test positivity by occupation can aid targeting of messaging for vaccination and testing and mitigation strategies for the current and future respiratory infection epidemics and pandemics. These results, obtained before availability of COVID-19 vaccines, can form a basis for comparison to evaluate impacts of vaccination and subsequent emergence of viral variants.

BACKGROUND: While other studies have reported estimates of COVID-19 vaccine uptake by broad occupational group, little is known about vaccine uptake by detailed occupational category. METHODS: Data on COVID-19 vaccination were provided by US adults ages ≥18 years old who responded to the Facebook/Delphi Group COVID-19 Trends and Impact Survey (Delphi US CTIS) in April-May 2021, reported working for pay in the past 4 weeks, and answered questions about their COVID-19 vaccine status. Percentages of occupational groups reporting having had at least one COVID-19 vaccination were weighted to resemble the US general population and calculated for 23 major occupational groups and 120 detailed occupational categories in 15 major groups. RESULTS: COVID-19 vaccine uptake for all 828,401 working adult respondents was 73.6%. Uptake varied considerably across the 23 major occupational groups, from 45.7% for Construction and Extraction to 87.9% for Education, Training, and Library. Percentage vaccinated was also very low for Installation, Maintenance, and Repair at 52.1% and Farming, Fishing, and Forestry at 53.9%. Among the 120 detailed occupational categories, the highest percentage vaccinated was 93.9% for Postsecondary Teacher and the three lowest values were 39.1% for Any Extraction Worker in Oil, Gas, Mining, or Quarrying; 40.1% for Vehicle or Mobile Equipment Mechanic, Installer, or Repairer; and 42.0% for Any Construction Trades Worker. CONCLUSION: Low vaccination percentages were seen in many US occupations by the end of May 2021, early in the period of widespread availability of vaccines for adults. These findings could help inform the deployment of occupation-specific vaccinepromotion activities during future viral epidemics and pandemics.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Identifying determinants of HIV reservoir levels may inform novel viral eradication strategies. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-infections were assessed as predictors of HIV proviral DNA level in 26 HIV RNA-suppressed Kenyan children starting antiretroviral therapy (ART) before 7 months of age. Earlier acquisition of CMV and EBV, and higher cumulative burden of systemic EBV DNA viremia were each associated with higher HIV DNA level in the reservoir after 24 months of ART, independent of HIV RNA levels over time. These data suggest delaying or containing CMV and EBV viremia may be novel strategies to limit HIV reservoir formation.

Background: Endemic and emerging respiratory viruses are a threat to public health, and a robust public health laboratory system is essential to ensure global health security. Objective: This program sought to expand molecular laboratory testing capacity to detect a broad range of respiratory pathogens in clinical respiratory specimens collected during disease surveillance and outbreak investigations. Methods: As a part of the Global Health Security Agenda (GHSA), the United States Centers for Disease Control and Prevention utilised the equipment and training infrastructure already in place at the World Health Organization National Influenza Centers to expand testing capacity for respiratory viruses in laboratories in GHSA partner countries. This was done through the provision of quality assured reagents, including multiplex platforms and technical guidance for laboratory staff, as well as the assessment of laboratory testing accuracy. Conclusion: Early findings illustrated that GHSA laboratories have been able to expand testing capacity using specimens from routine surveillance, as well as from outbreak situations.

Electronic vapor products (EVPs) comprise a diverse group of devices, including electronic cigarettes (e-cigarettes). EVP users inhale an aerosol that typically contains nicotine, flavorings, and other additives (1). Nicotine is a developmental toxicant that adversely affects pregnancy and infant outcomes (2). Data from the 2015 Pregnancy Risk Assessment Monitoring System (PRAMS) for Oklahoma and Texas were analyzed to estimate population-based EVP use among women with a recent live birth. EVP use before pregnancy (defined as >3 months before pregnancy) and around the time of pregnancy (defined as any time during the 3 months before pregnancy, the last 3 months of pregnancy, or 2-6 months after delivery), reasons for EVP use, and dual use of EVPs and cigarettes were assessed. Prevalence of EVP use was 10.4% before pregnancy and 7.0% around the time of pregnancy, including 1.4% during the last 3 months of pregnancy. Among women using EVPs during the last 3 months of pregnancy, 38.4% reported use of EVPs containing nicotine, and 26.4% were unsure of nicotine content. Among women who had used EVPs and cigarettes, dual use prevalence was 38.0% in the 3 months before pregnancy, 7.7% during the last 3 months of pregnancy, and 11.8% in the 2-6 months after delivery. The most frequently reported reasons for EVP use around the time of pregnancy were curiosity (54.0%), the perception that EVPs might help with quitting or reducing cigarette smoking (45.2%), and the perception of reduced harm to the mother, when compared with cigarette smoking (45.2%). Clear messages that EVP use is not safe during pregnancy are needed, and broad, barrier-free access to evidence-based tobacco cessation strategies need to be made available.

In 1961, Dr. Robert Guthrie initiated the collection of blood as dried spots on filter paper for testing newborns for the detection of phenylketonuria (PKU) (1, 2). He analyzed these dried blood spot (DBS) specimens with a bacterial inhibition test that he developed to measure phenylalanine (2). This combination of easily transportable specimens and an inexpensive, simple test made large-scale testing for PKU possible. As a result of Guthrie’s efforts, the successful introduction of DBS as a source for PKU screening eventually led to population-based screening for over 32 disorders for all newborns in the United States from only a few blood drops collected from a heel stick and absorbed into special filter paper. | Today, newborn screening (NBS) is the largest population-based genetic screening effort in the U.S. and is performed worldwide (3). The detection of treatable, inherited congenital disorders is a major public health responsibility. The U.S. Centers for Disease Control and Prevention has recognized newborn screening as one of the ten great public health achievements in the United States in the first decade on the 21st century (4). Newborn screening programs are designed to detect asymptomatic newborns that are at higher risk for certain diseases from those who may not, using DBS specimens collected 24–72 hours after birth. Babies that are screen-positive are rapidly followed-up with a diagnostic confirmation and appropriate treatment that helps to prevent mental retardation, premature death and other deleterious clinical outcomes. Improvements in technology and the expansion of the recommended uniform newborn screening panel of diseases have led to earlier life-saving treatment and intervention for at least 12,000 additional newborns each year in the United States with selected genetic, hearing and endocrine disorders (5).

Radiochemical neutron activation analysis (RNAA) was used to measure arsenic at four levels in standard reference material (SRM) 955c Toxic Elements in Caprine Blood and at two levels in SRM 2668 Toxic Elements in Frozen Human Urine for the purpose of providing mass concentration values for certification. Samples were freeze-dried prior to analysis followed by neutron irradiation for 3 h at a fluence rate of 1 × 10^14 cm^−2 s^−1. After sample dissolution in perchloric and nitric acids, arsenic was separated from the matrix either by retention on hydrated manganese dioxide (urine) or by extraction into zinc diethyldithiocarbamate in chloroform (blood). ^76As was quantified by gamma-ray spectroscopy. Differences in chemical yield and counting geometry between samples and standards were monitored by measuring the count rate of a ^77As tracer added before sample dissolution. RNAA results were combined with inductively coupled plasma-mass spectrometry values from National Institute of Standards and Technology and collaborating laboratories to provide certified values of 10.81 ± 0.54 and 213.1 ± 0.73 μg/L for SRM 2668 Levels I and II, and certified values of 21.66 ± 0.73, 52.7 ± 1.1, and 78.8 ± 4.9 μg/L for SRM 955c Levels II–IV, respectively. Because of discrepancies between values obtained by different methods for SRM 955c Level I, an information value of <5 μg/L was assigned for this material.

The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health (NIH), has developed a Standard Reference Material (SRM) to support technology development in metabolomics research. SRM 1950 Metabolites in Human Plasma is intended to have metabolite concentrations that are representative of those found in adult human plasma. The plasma used in the preparation of SRM 1950 was collected from both male and female donors, and donor ethnicity targets were selected based upon the ethnic makeup of the U.S. population. Metabolomics research is diverse in terms of both instrumentation and scientific goals. This SRM was designed to apply broadly to the field, not toward specific applications. Therefore, concentrations of approximately 100 analytes, including amino acids, fatty acids, trace elements, vitamins, hormones, selenoproteins, clinical markers, and perfluorinated compounds (PFCs), were determined. Value assignment measurements were performed by NIST and the Centers for Disease Control and Prevention (CDC). SRM 1950 is the first reference material developed specifically for metabolomics research.

Excessive gestational weight gain (GWG) predicts adverse pregnancy outcomes and later obesity risk for both mother and child. Women who receive GWG advice from their obstetric clinicians are more likely to gain the recommended amount, but many clinicians do not counsel their patients on GWG, pointing to the need for new strategies. Electronic medical records (EMRs) are a useful tool for tracking weight and supporting guideline-concordant care, but their use for care related to GWG has not been evaluated. We performed in-depth interviews with 16 obstetric clinicians from a multi-site group practice in Massachusetts that uses an EMR. We recorded, transcribed, coded, and analyzed the interviews using immersion-crystallization. Many respondents believed that GWG had "a lot" of influence on pregnancy and child health outcomes but that their patients did not consider it important. Most indicated that excessive GWG was a big or moderate problem in their practice, and that inadequate GWG was rarely a problem. All used an EMR feature that calculates total GWG at each visit. Many were enthusiastic about additional EMR-based supports, such as a reference for recommended GWG for each patient based on pre-pregnancy body mass index, a "growth chart" to plot actual and recommended GWG, and an alert to identify out-of-range gains, features which many felt would remind them to counsel patients about excessive weight gain. Additional decision support tools within EMRs would be well received by many clinicians and may help improve the frequency and accuracy of GWG tracking and counseling.

The external quality assessment of 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) genotyping by de Beer et al. reveals issues with its international performance (5). Detailed analysis of the data was confounded by the complexity of the participants. The five genotyping laboratories in Canada and the United States participating in this study use similar typing protocols based on the standardized protocol proposed by Supply et al. (8) and developed in collaboration with each other. Systems for routine handling of samples and data management are well established. Quality control (QC) and assurance measures include routine testing of the Mycobacterium tuberculosis strain H37Rv and repeat testing of 1% of isolates at an external laboratory. The laboratorians conducting the analysis have at a minimum 5 years of experience performing MIRU-VNTR typing. This cohesiveness allows for a more in-depth analysis of the data collected by de Beer et al. | Each laboratory reported 24-locus MIRU-VNTR results for the proficiency testing panel of 30 DNA samples (including 10 pairs of duplicates), and their performance is summarized in Table 1. Reproducibility as calculated at the sample level and disregarding missing results ranged from 93% to 100%, and typeability as calculated by the percentage of loci with a reportable result ranged from 98.9% to 100%. Here we present a detailed description of the 38 observed discrepancies to provide a more complete understanding of the performance of MIRU-VNTR typing in our laboratories.

Swine influenza viruses (SIV), have been shown to sporadically infect humans, and are infrequently identified by Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypable influenza A virus samples. Real-time RT-PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N.Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data of the first two viruses, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. Analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per-reaction and 10(-1.3 approximately -0.7) ID(50) per-reaction for cultured viruses. Cross reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation.