Investigation of False Positive Results with an Oral Fluid Rapid HIV-1/2 Antibody Test

BACKGROUND: In March 2004, the OraQuick® rapid HIV antibody test became the first rapid HIV test approved by the US Food and Drug Administration for use on oral fluid specimens. Test results are available in 20 minutes, and the oral fluid test is non-invasive. From August 2004–June 2005, we investigated a sudden increase in false-positive results occurring in a performance study of OraQuick® oral-fluid rapid HIV tests in Minnesota. METHODOLOGY/PRINCIPAL FINDINGS: In a field investigation, we reviewed performance study data on oral-fluid and whole-blood OraQuick® rapid HIV test device lots and expiration dates and assessed test performance and interpretation with oral-fluid and whole-blood specimens by operators who reported false-positive results. We used multivariate logistic regression to evaluate client demographic and risk characteristics associated with false-positive results. Next, we conducted an incidence study of false-positive OraQuick rapid HIV tests in nine US cities and tested both oral-fluid and finger-stick whole-blood specimens from clients; reactive tests were confirmed with Western blot. Sixteen (4.1%) false-positive oral-fluid results occurred in the performance study from April 15, 2004 through August 31, 2004 with unexpired devices from six test lots among 388 HIV-uninfected clients (specificity, 95.9%; 95% CI: 93.4–97.6). Three test operators who had reported false-positive results performed and interpreted the test according to package-insert instructions. In multivariate analysis, only older age was significantly associated with false-positive results (adjusted odds ratio = 4.5, 95% CI: 1.2–25.7). In the incidence study, all valid oral-fluid and whole-blood results from 2,268 clients were concordant and no false-positive results occurred (100% specificity). CONCLUSIONS/SIGNIFICANCE: The field investigation did not identify a cause for the increase in false-positive oral-fluid results, and the incidence study detected no false-positive results. The findings suggest this was an isolated cluster; the test's overall performance was as specified by the manufacturer

False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women

Objective: Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). Design: To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. Methods: Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. Results: HIV prevalence was 0.06 % among 921,438 pregnant women and 1.34 % among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14 % vs. 0.21%, odds ratio 0.65 [95 % confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p,0.01) to have Western blot-negative (52.9 % vs. 9.8%) and indeterminate results (17.0 % vs. 3.7%) and lower PPV (30 % vs. 87%). The p24 band was detected more often among pregnant women (p,0.01). Conclusions: False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

First population-level effectiveness evaluation of a national programme to prevent HIV transmission from mother to child, South Africa

BACKGROUND : There is a paucity of data on the national population-level effectiveness of preventing mother-tochild transmission (PMTCT) programmes in high-HIVprevalence, resource-limited settings. We assessed national PMTCT impact in South Africa (SA), 2010. METHODS : A facility-based survey was conducted using a stratified multistage, cluster sampling design. A nationally representative sample of 10 178 infants aged 4–8 weeks was recruited from 565 clinics. Data collection included caregiver interviews, record reviews and infant dried blood spots to identify HIV-exposed infants (HEI) and HIV-infected infants. During analysis, self-reported antiretroviral (ARV) use was categorised: 1a: triple ARV treatment; 1b: azidothymidine >10 weeks; 2a: azidothymidine ≤10 weeks; 2b: incomplete ARV prophylaxis; 3a: no antenatal ARV and 3b: missing ARV information. Findings were adjusted for non-response, survey design and weighted for live-birth distributions. RESULTS : Nationally, 32% of live infants were HEI; early mother-to-child transmission (MTCT) was 3.5% (95% CI 2.9% to 4.1%). In total 29.4% HEI were born to mothers on triple ARV treatment (category 1a) 55.6% on prophylaxis (1b, 2a, 2b), 9.5% received no antenatal ARV (3a) and 5.5% had missing ARV information (3b). Controlling for other factors groups, 1b and 2a had similar MTCT to 1a (Ref; adjusted OR (AOR) for 1b, 0.98, 0.52 to 1.83; and 2a, 1.31, 0.69 to 2.48). MTCT was higher in group 2b (AOR 3.68, 1.69 to 7.97). Within group 3a, early MTCT was highest among breastfeeding mothers 11.50% (4.67% to 18.33%) for exclusive breast feeding, 11.90% (7.45% to 16.35%) for mixed breast feeding, and 3.45% (0.53% to 6.35%) for no breast feeding). Antiretroviral therapy or >10 weeks prophylaxis negated this difference (MTCT 3.94%, 1.98% to 5.90%; 2.07%, 0.55% to 3.60% and 2.11%, 1.28% to 2.95%, respectively). CONCLUSIONS : SA, a high-HIV-prevalence middle income country achieved <5% MTCT by 4–8 weeks post partum. The long-term impact on PMTCT on HIV-free survival needs urgent assessment.South African National Research Foundationhttp://jech.bmj.comhb201

Definitions, Foundations and Associations of Physical Literacy: A Systematic Review

Background: The concept of physical literacy has stimulated increased research attention in recent years—being deployed in physical education, sport participation, and the promotion of physical activity. Independent research groups currently operationalize the construct differently. Objective The purpose of this systematic review was to conduct a systematic review of the physical literacy construct,as reflected in contemporary research literature. Methods: Five databases were searched using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for systematic reviews. Inclusion criteria were English language, peer reviewed, published by March 2016, and seeking to conceptualize physical literacy. Articles that met these criteria were analysed in relation to three core areas: properties/attributes, philosophicalfoundations and theoretical associations with other constructs. A total of 50 published articles met the inclusion criteria and were analysed qualitatively using inductive thematic analysis.Results: The thematic analysis addressed the three core areas. Under definitions, core attributes that define physical literacy were identified, as well as areas of conflict between different approaches currently being adopted. One relatively clear philosophical approach was prominent in approximately half of the papers, based on a monist/holistic ontology and phenomenological epistemology. Finally, theanalysis identified a number of theoretical associations, including health, physical activity and academic performance.Conclusions: Current literature contains different representations of the physical literacy construct. The costs and benefits of adopting an exclusive approach versus pluralism are considered. Recommendations for both researchers and practitioners focus on identifying and clearly articulating the definitions, philosophical assumptions and expected outcomes prior to evaluating the effectiveness of this emerging concept

Prophylactic Melatonin for Delirium in Intensive Care (Pro-MEDIC): Study protocol for a randomised controlled trial

Background: Delirium is an acute state of brain dysfunction characterised by fluctuating inattention and cognitive disturbances, usually due to illness. It occurs commonly in the intensive care unit (ICU), and it is associated with greater morbidity and mortality. It is likely that disturbances of sleep and of the day-night cycle play a significant role. Melatonin is a naturally occurring, safe and cheap hormone that can be administered to improve sleep. The main aim of this trial will be to determine whether prophylactic melatonin administered to critically ill adults, when compared with placebo, decreases the rate of delirium. Methods: This trial will be a multi-centre, randomised, placebo-controlled study conducted in closed ICUs in Australia. Our aim is to enrol 850 adult patients with an expected ICU length of stay (LOS) of 72h or more. Eligible patients for whom there is consent will be randomised to receive melatonin 4mg enterally or placebo in a 1:1 ratio according to a computer-generated randomisation list, stratified by site. The study drug will be indistinguishable from placebo. Patients, doctors, nurses, investigators and statisticians will be blinded. Melatonin or placebo will be administered once per day at 21:00 until ICU discharge or 14days after enrolment, whichever occurs first. Trained staff will assess patients twice daily to determine the presence or absence of delirium using the Confusion Assessment Method for the ICU score. Data will also be collected on demographics, the overall prevalence of delirium, duration and severity of delirium, sleep quality, participation in physiotherapy sessions, ICU and hospital LOS, morbidity and mortality, and healthcare costs. A subgroup of 100 patients will undergo polysomnographic testing to further evaluate the quality of sleep. Discussion: Delirium is a significant issue in ICU because of its frequency and associated poorer outcomes. This trial will be the largest evaluation of melatonin as a prophylactic agent to prevent delirium in the critically ill population. This study will also provide one of the largest series of polysomnographic testing done in ICU. Trial registration: Australian New Zealand Clinical Trial Registry (ANZCTR) number: ACTRN12616000436471. Registered on 20 December 2015

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications

Sequencing-based DNA methylation profiling methods are comprehensive and, as accuracy and affordability improve, will increasingly supplant microarrays for genome-scale analyses. Here, four sequencing-based methodologies were applied to biological replicates of human embryonic stem cells to compare their CpG coverage genome-wide and in transposons, resolution, cost, concordance and its relationship with CpG density and genomic context. The two bisulfite methods reached concordance of 82% for CpG methylation levels and 99% for non-CpG cytosine methylation levels. Using binary methylation calls, two enrichment methods were 99% concordant, while regions assessed by all four methods were 97% concordant. To achieve comprehensive methylome coverage while reducing cost, an approach integrating two complementary methods was examined. The integrative methylome profile along with histone methylation, RNA, and SNP profiles derived from the sequence reads allowed genome-wide assessment of allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

‘Measuring’ Physical Literacy and Related Constructs: A Systematic Review of Empirical Findings

BACKGROUND:The concept of physical literacy has received increased research and international attention recently. Where intervention programs and empirical research are gaining momentum, their operationalizations differ significantly.OBJECTIVE:The objective of this study was to inform practice in the measure/assessment of physical literacy via a systematic review of research that has assessed physical literacy (up to 14 June, 2017).METHODS:Five databases were searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines, with 32 published articles meeting the inclusion criteria. English-language, peer-reviewed published papers containing empirical studies of physical literacy were analyzed using inductive thematic analysis.RESULTS:Qualitative methods included: (1) interviews; (2) open-ended questionnaires; (3) reflective diaries; (4) focus groups; (5) participant observations; and (6) visual methods. Quantitative methods included: (1) monitoring devices (e.g., accelerometers); (2) observations (e.g., of physical activity or motor proficiency); (3) psychometrics (e.g., enjoyment, self-perceptions); (4) performance measures (e.g., exergaming, objective times/distances); (5) anthropometric measurements; and (6) one compound measure. Of the measures that made an explicit distinction: 22 (61%) examined the physical domain, eight (22%) the affective domain; five (14%) the cognitive domain; and one (3%) combined three domains (physical, affective, and cognitive) of physical literacy. Researchers tended to declare their philosophical standpoint significantly more in qualitative research compared with quantitative research.CONCLUSIONS:Current research adopts diverse often incompatible methodologies in measuring/assessing physical literacy. Our analysis revealed that by adopting simplistic and linear methods, physical literacy cannot be measured/assessed in a traditional/conventional sense. Therefore, we recommend that researchers are more creative in developing integrated philosophically aligned approaches to measuring/assessing physical literacy. Future research should consider the most recent developments in the field of physical literacy for policy formation