Situation of HIV infections and STIs in the United Kingdom in 2007.

In the United Kingdom (UK) in 2007, an estimated 77,400 persons were living with human immunodeficiency virus (HIV) of whom 28% are unaware of their infection. A total of 7,734 persons were newly diagnosed with HIV infection in 2007, of which 31% were diagnosed late. This highlights the need for wider HIV testing, especially in those areas with a high diagnosed prevalence, as recommended in recent national guidelines. Among newly diagnosed cases of HIV in 2007, 41% acquired their infection through sex between men (four in five of whom acquired their infection in the UK) and 55% through heterosexual contact (four in five of whom acquired their infection abroad, mainly in sub-Saharan Africa). Young persons aged 16 to 24 years are disproportionally affected by sexually transmitted diseases (STIs) accounting for 65% of genital chlamydia infections, 50% of cases of genital warts and 50% of cases of gonorrhoea that were diagnosed in 2007

The diverse nature of island isolation and its effect on land bridge insular faunas

Aim: Isolation is a key factor in island biology. It is usually defined as the distance to the geographically nearest mainland, but many other definitions exist. We explored how testing different isolation indices affects the inference of impacts of isolation on faunal characteristics. We focused on land bridge islands and compared the relationships of many spatial and temporal (i.e., through time) isolation indices with community‐, population‐ and individual‐level characteristics (species richness, population density and body size, respectively). Location: Aegean Sea islands, Greece. Time period: Current. Taxon: Many animal taxa. Methods: We estimated 21 isolation indices for 205 islands and recorded species richness data for 15 taxa (invertebrates and vertebrates). We obtained body size data for seven lizard species and population density data for three. We explored how well indices predict each characteristic, in each taxon, by conducting a series of ordinary least squares regressions (controlling for island area when needed) and a meta‐analysis. Results: Isolation was significantly (and negatively) associated with species richness in 10 of 15 taxa. It was significantly (and positively) associated with body size in only one of seven species and was not associated with population density. The effect of isolation on species richness was much weaker than that of island area, regardless of the index tested. Spatial indices generally out‐performed temporal indices, and indices directly related to the mainland out‐performed those related mainly to neighbouring islands. No index was universally superior to others, including the distance to the geographically nearest mainland. Main conclusions: The choice of index can alter our perception of the impacts of isolation on biological patterns. The nearly automatic, ubiquitous use of distance to the geographically nearest mainland misrepresents the complexity of the effects of isolation. We recommend the simultaneous testing of several indices that represent different aspects of isolation, in order to produce more constructive and thorough investigations and avoid imprecise inference

Neuroscience in gambling policy and treatment: an interdisciplinary perspective

Neuroscientific explanations of gambling disorder can help people make sense of their experiences and guide the development of psychosocial interventions. However, the societal perceptions and implications of these explanations are not always clear or helpful. Two workshops in 2013 and 2014 brought together multidisciplinary researchers aiming to improve the clinical and policy-related effects of neuroscience research on gambling. The workshops revealed that neuroscience can be used to improve identification of the dangers of products used in gambling. Additionally, there was optimism associated with the diagnostic and prognostic uses of neuroscience in problem gambling and the provision of novel tools (eg, virtual reality) to assess the effectiveness of new policy interventions before their implementation. Other messages from these workshops were that neuroscientific models of decision making could provide a strong rationale for precommitment strategies and that interdisciplinary collaborations are needed to reduce the harms of gambling

The mothers, Omega-3 and mental health study

<p>Abstract</p> <p>Background</p> <p>Major depressive disorder (MDD) during pregnancy and postpartum depression are associated with significant maternal and neonatal morbidity. While antidepressants are readily used in pregnancy, studies have raised concerns regarding neurobehavioral outcomes in exposed infants. Omega-3 fatty acid supplementation, most frequently from fish oil, has emerged as a possible treatment or prevention strategy for MDD in non-pregnant individuals, and may have beneficial effects in pregnant women. Although published observational studies in the psychiatric literature suggest that maternal docosahexaenoic acid (DHA) deficiency may lead to the development of MDD in pregnancy and postpartum, there are more intervention trials suggesting clinical benefit for supplementation with eicosapentaenoic acid (EPA) in MDD.</p> <p>Methods/Design</p> <p>The Mothers, Omega-3 and Mental Health study is a double blind, placebo-controlled, randomized controlled trial to assess whether omega-3 fatty acid supplementation may prevent antenatal and postpartum depressive symptoms among pregnant women at risk for depression. We plan to recruit 126 pregnant women at less than 20 weeks gestation from prenatal clinics at two health systems in Ann Arbor, Michigan and the surrounding communities. We will follow them prospectively over the course of their pregnancies and up to 6 weeks postpartum. Enrolled participants will be randomized to one of three groups: a) EPA-rich fish oil supplement (1060 mg EPA plus 274 mg DHA) b) DHA-rich fish oil supplement (900 mg DHA plus 180 mg EPA; or c) a placebo. The primary outcome for this study is the Beck Depression Inventory (BDI) score at 6 weeks postpartum. We will need to randomize 126 women to have 80% power to detect a 50% reduction in participants' mean BDI scores with EPA or DHA supplementation compared with placebo. We will also gather information on secondary outcome measures which will include: omega-3 fatty acid concentrations in maternal plasma and cord blood, pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in maternal and cord blood, need for and dosage of antidepressant medications, and obstetrical outcomes. Analyses will be by intent to treat.</p> <p>Discussion</p> <p>This study compares the relative effectiveness of DHA and EPA at preventing depressive symptoms among pregnant women at risk.</p> <p>Trial registration</p> <p>Clinical trial registration number: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00981877">NCT00711971</a></p

Nasal continuous positive airway pressure improves myocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) has been associated with cardiovascular disease (CVD), but whether OSA is an independent risk factor for CVD is controversial. The purpose of this study is to determine if patients with OSA have subclinical cardiovascular disease that is detectable by multi-modality cardiovascular imaging and whether these abnormalities improve after nasal continuous positive airway pressure (nCPAP).</p> <p>Results</p> <p>Of the 35 consecutive subjects with newly diagnosed moderate to severe OSA recruited from the Stanford Sleep Disorders Clinic, 20 patients were randomized to active vs. sham nCPAP. Active nCPAP was titrated to pressures that would prevent sleep disordered breathing based on inpatient polysomnography. OSA patients had baseline vascular function abnormalities including decreased myocardial perfusion reserve (MPR), brachial flow mediated dilation (FMD) and nitroglycerin-induced coronary vasodilation. Patients randomized to active nCPAP had improvement of MPR (1.5 ± 0.5 vs. 3.0 ± 1.3, p = 0.02) and brachial FMD (2.5% ± 5.7% vs. 9.0% ± 6.5%, p = 0.03) after treatment, but those randomized to sham nCPAP showed no significant improvement. There were no significant changes seen in chamber sizes, systolic and diastolic function, valvular function and coronary vasodilation to nitroglycerin.</p> <p>Conclusions</p> <p>Patients with moderate to severe OSA had decreased MPR and brachial FMD that improved after 3 months of nCPAP. These findings suggest that relief of apnea in OSA may improve microvascular disease and endothelial dysfunction, which may prevent the development of overt cardiovascular disease. Further study in a larger patient population may be warranted.</p

Pastoralism and Emergent Complex Settlement in the Middle Bronze Age, Azerbaijan: Isotopic analyses of mobility strategies in transformation

Objectives. This article explores the scale and seasonal patterns of mobility at the complex settlement site of Qızqala during the Middle Bronze Age (2400–1,500 BCE). By integrating human bone, teeth, and environmental samples this research tests the hypothesis of the persistent importance of community-wide seasonal pastoral transhumance during the early formation of complex settlement systems of the South Caucasus. Methods. This research applies stable oxygen and radiogenic strontium isotope analyses on incremental samples of human tooth enamel, bulk tooth enamel, and bone to resolve mobility patterns. Sequential and bulk sampling techniques elucidate seasonal and residential mobility behaviors. Extensive environmental isotope samples of plant and water were collected through regional survey and establish local and regional isotopic baselines, which are compared to human isotope analysis results. Results. Qızqala individuals exhibit low isotopic variability compared to regional contemporaries. 87Sr/86Sr ratios from human remains indicate seasonal and residential isotopic variability within the baseline ranges of local landscapes. δ18O values display erratic patterns, but correspond to seasonal variability with fluctuations between highland and lowland altitudinal zone baseline values. Conclusions. Results suggest that isotopic analysis of multiple elements and sequential enamel samples offers finer resolution on the complexities of human mobility strategies and elucidate the daily lives of often overlooked mobile populations. Higher resolution of individual mobility reveals shared routine behaviors that underscore the importance of diverse social collaborations in forming complex polities in the South Caucasus

The Princeton Protein Orthology Database (P-POD): A Comparative Genomics Analysis Tool for Biologists

Many biological databases that provide comparative genomics information and tools are now available on the internet. While certainly quite useful, to our knowledge none of the existing databases combine results from multiple comparative genomics methods with manually curated information from the literature. Here we describe the Princeton Protein Orthology Database (P-POD, http://ortholog.princeton.edu), a user-friendly database system that allows users to find and visualize the phylogenetic relationships among predicted orthologs (based on the OrthoMCL method) to a query gene from any of eight eukaryotic organisms, and to see the orthologs in a wider evolutionary context (based on the Jaccard clustering method). In addition to the phylogenetic information, the database contains experimental results manually collected from the literature that can be compared to the computational analyses, as well as links to relevant human disease and gene information via the OMIM, model organism, and sequence databases. Our aim is for the P-POD resource to be extremely useful to typical experimental biologists wanting to learn more about the evolutionary context of their favorite genes. P-POD is based on the commonly used Generic Model Organism Database (GMOD) schema and can be downloaded in its entirety for installation on one's own system. Thus, bioinformaticians and software developers may also find P-POD useful because they can use the P-POD database infrastructure when developing their own comparative genomics resources and database tools

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

&lt;p&gt;Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.&lt;/p&gt; &lt;p&gt;Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate &#60;60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.&lt;/p&gt; &lt;p&gt;Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.&lt;/p&gt

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Background: Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP). Methods and Findings: Three population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression. Conclusion: The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification