Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium

Background The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods. Methods Data were assembled from a subset of seven of 19 international sites in the Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium. In this analysis, the cohort was restricted to women aged 19–40 years with information about onset of depressive symptoms in the perinatal period and complete prospective data for the ten-item Edinburgh postnatal depression scale (EPDS). Principal components and common factor analysis were used to identify symptom dimensions in the EPDS. The National Institute of Mental Health research domain criteria functional constructs of negative valence and arousal were applied to the EPDS dimensions that reflect states of depressed mood, anhedonia, and anxiety. We used k-means clustering to identify subtypes of women sharing symptom patterns. Univariate and bivariate statistics were used to describe the subtypes. Findings Data for 663 women were included in these analyses. We found evidence for three underlying dimensions measured by the EPDS: depressed mood, anxiety, and anhedonia. On the basis of these dimensions, we identified five distinct subtypes of perinatal depression: severe anxious depression, moderate anxious depression, anxious anhedonia, pure anhedonia, and resolved depression. These subtypes have clear differences in symptom quality and time of onset. Anxiety and anhedonia emerged as prominent symptom dimensions with post-partum onset and were notably severe. Interpretation Our findings show that there might be different types and severity of perinatal depression with varying time of onset throughout pregnancy and post partum. These findings support the need for tailored treatments that improve outcomes for women with perinatal depression

Roadless wilderness area determines forest elephant movements in the Congo Basin

A dramatic expansion of road building is underway in the Congo Basin fuelled by private enterprise, international aid, and government aspirations. Among the great wilderness areas on earth, the Congo Basin is outstanding for its high biodiversity, particularly mobile megafauna including forest elephants (Loxodonta africana cyclotis). The abundance of many mammal species in the Basin increases with distance from roads due to hunting pressure, but the impacts of road proliferation on the movements of individuals are unknown. We investigated the ranging behaviour of forest elephants in relation to roads and roadless wilderness by fitting GPS telemetry collars onto a sample of 28 forest elephants living in six priority conservation areas. We show that the size of roadless wilderness is a strong determinant of home range size in this species. Though our study sites included the largest wilderness areas in central African forests, none of 4 home range metrics we calculated, including core area, tended toward an asymptote with increasing wilderness size, suggesting that uninhibited ranging in forest elephants no longer exists. Furthermore we show that roads outside protected areas which are not protected from hunting are a formidable barrier to movement while roads inside protected areas are not. Only 1 elephant from our sample crossed an unprotected road. During crossings her mean speed increased 14-fold compared to normal movements. Forest elephants are increasingly confined and constrained by roads across the Congo Basin which is reducing effective habitat availability and isolating populations, significantly threatening long term conservation efforts. If the current road development trajectory continues, forest wildernesses and the forest elephants they contain will collapse

Antipsychotic medication versus psychological intervention versus a combination of both in adolescents with first-episode psychosis (MAPS): a multicentre, three-arm, randomised controlled pilot and feasibility study

Background Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy [CBT] and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis. Methods We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14–18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433. Findings Of 101 patients referred to the study, 61 patients (mean age 16·3 years [SD 1·3]) were recruited from April 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 [84%] participants retained at the 6-month primary endpoint), a high rate of adherence to psychological intervention (defined as six or more sessions of CBT; in 32 [82%] of 39 participants in the monotherapy and combined groups), and a moderate rate of adherence to antipsychotic medication (defined as at least 6 consecutive weeks of exposure to antipsychotics; in 28 [65%] of 43 participants in the monotherapy and combined groups). Mean scores for PANSS total at the 6-month primary endpoint were 68·6 (SD 17·3) for antipsychotic monotherapy (6·2 points lower than at randomisation), 59·8 (13·7) for psychological intervention (13·1 points lower than at randomisation), and 62·0 (15·9) for antipsychotics plus psychological intervention (13·9 points lower than at randomisation). A good clinical response at 6 months (defined as ≥50% improvement in PANSS total score) was achieved in four (22%) of 18 patients receiving antipsychotic monotherapy, five (31%) of 16 receiving psychological intervention, and five (29%) of 17 receiving antipsychotics plus psychological intervention. In as-treated groups, serious adverse events occurred in eight [35%] of 23 patients in the combined group, two [13%] of 15 in the antipsychotics group, four [24%] of 17 in the psychological intervention group, and four [80%] of five who did not receive any treatment. No serious adverse events were considered to be related to participation in the trial. Interpretation This trial is the first to show that a head-to-head clinical trial comparing psychological intervention, antipsychotics, and their combination is safe in young people with first-episode psychosis. However, the feasibility of a larger trial is unclear because of site-specific recruitment challenges, and amendments to trial design would be needed for an adequately powered clinical and cost-effectiveness trial that provides robust evidence

Accommodating Dynamic Oceanographic Processes and Pelagic Biodiversity in Marine Conservation Planning

Pelagic ecosystems support a significant and vital component of the ocean's productivity and biodiversity. They are also heavily exploited and, as a result, are the focus of numerous spatial planning initiatives. Over the past decade, there has been increasing enthusiasm for protected areas as a tool for pelagic conservation, however, few have been implemented. Here we demonstrate an approach to plan protected areas that address the physical and biological dynamics typical of the pelagic realm. Specifically, we provide an example of an approach to planning protected areas that integrates pelagic and benthic conservation in the southern Benguela and Agulhas Bank ecosystems off South Africa. Our aim was to represent species of importance to fisheries and species of conservation concern within protected areas. In addition to representation, we ensured that protected areas were designed to consider pelagic dynamics, characterized from time-series data on key oceanographic processes, together with data on the abundance of small pelagic fishes. We found that, to have the highest likelihood of reaching conservation targets, protected area selection should be based on time-specific data rather than data averaged across time. More generally, we argue that innovative methods are needed to conserve ephemeral and dynamic pelagic biodiversity

Disinfection with sodium hypochlorite in hospital environmental surfaces in the reduction of contamination and infection prevention: a systematic review

OBJECTIVETo search for evidence of the efficiency of sodium hypochlorite on environmental surfaces in reducing contamination and prevention of healthcare-associated infection HAIs.METHODSystematic review in accordance with the Cochrane Collaboration.RESULTSWe analyzed 14 studies, all controlled trials, published between 1989-2013. Most studies resulted in inhibition of microorganism growth. Some decreased infection, microorganism resistance and colonization, loss of efficiency in the presence of dirty and surface-dried viruses.CONCLUSIONThe hypochlorite is an effective disinfectant, however, the issue of the direct relation with the reduction of HAIs remains. The absence of control for confounding variables in the analyzed studies made the meta-analysis performance inadequate. The evaluation of internal validity using CONSORT and TREND was not possible because its contents were not appropriate to laboratory and microbiological studies. As a result, there is an urgent need for developing specific protocol for evaluating such studies

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, abeta, and alzheimer's disease.

Background: The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD). Methodology/Principal findings: We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants. Four of these showed significant association with IDE transcript levels in samples from 194 LOAD cerebella. The strongest, rs6583817, which has not previously been reported, showed unequivocal association (p = 1.5x10(-8), fold-increase = 2.12,); the eleven haplotypes were also significantly associated with transcript levels (global p = 0.003). Using an in vitro dual luciferase reporter assay, we found that rs6583817 increases reporter gene expression in Be(2)-C (p = 0.006) and HepG2 (p = 0.02) cell lines. Furthermore, using data from a recent genome-wide association study of two Croatian isolated populations (n = 1,879), we identified a proxy for rs6583817 that associated significantly with decreased plasma Abeta40 levels (ss = -0.124, p = 0.011) and total measured plasma Abeta levels (b = -0.130, p = 0.009). Finally, rs6583817 was associated with decreased risk of LOAD in 3,891 AD cases and 3,605 controls. (OR = 0.87, p = 0.03), and the eleven IDE haplotypes (global p = 0.02) also showed significant association. Conclusions: Thus, a previously unreported variant unequivocally associated with increased IDE expression was also associated with reduced plasma Ass40 and decreased LOAD susceptibility. Genetic association between LOAD and IDE has been difficult to replicate. Our findings suggest that targeted testing of expression SNPs (eSNPs) strongly associated with altered transcript levels in autopsy brain samples may be a powerful way to identify genetic associations with LOAD that would otherwise be difficult to detect

A three-arm feasibility randomised controlled trial comparing antipsychotic medication to psychological intervention to a combined treatment in adolescents with first episode psychosis: The Managing Adolescent first episode Psychosis Study (MAPS)

Background: The evidence base for treatments for early-onset psychosis (EOP) is limited and of low quality. Current guidance for the treatment of EOP is mostly extrapolated from trials in adult populations. NICE, in the United Kingdom (UK), make a specific research recommendation for the evaluation of clinical and cost-effectiveness of antipsychotics (AP), versus psychological intervention (cognitive behaviour therapy [CBT] and family intervention), versus combination treatment for EOP. The National Institute for Health Research (NIHR) in the UK commissioned this research to establish feasibility and acceptability of a definitive trial examining these three treatment options. Methods: We conducted a multi-site, Prospective Randomised Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing AP monotherapy with psychological intervention monotherapy (PI) plus a combination of these treatments in 14-18-year olds with a first episode of psychosis. We recruited participants from seven United Kingdom sites. Participants were followed-up at six and 12 months. Cognitive behavioural therapy incorporated up to 26 sessions over 6 months plus up to four booster sessions. Family intervention included up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. The primary outcome was feasibility data (recruitment, retention, acceptability) and the main effectiveness outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 6 months. We conducted a repeated-measures analysis of the proposed primary outcome (PANSS) and the secondary outcome, the Questionnaire about the Process of Recovery (QPR) using a mixed effects model to account for the discrete timing of the follow-up assessments and adjusted for site. Safety outcomes were reported on the basis of as treated status defined as any one session of CBT or any one dose of APs; descriptive statistics are reported for safety outcomes. The study was prospectively registered on 27th February 2017, http://www.isrctn.com/ISRCTN80567433. Findings: 61 patients (aged 14-18 years; mean 16.3, SD 1.3) were recruited from 1st April 2017 to 31st October 2018, 18 were assigned to psychological intervention, 22 to antipsychotics and 21 to the combination. The feasibility of recruitment was unclear, since the trial only recruited 61 of a target of 90 participants. The study had a low referral: randomisation ratio (101:61), high rates of retention (>80%), high rates of adherence for psychological intervention (82.1%) defined as 6 or more sessions of CBT, and moderate rates of adherence for antipsychotic medication (65.1%), defined as 6 or more consecutive weeks of APs. The median number of sessions for CBT for those in the PI arm was 14 (IQR 9, 23) and 15 in the combined arm (IQR 9, 17). Of those in receipt of APs the mean duration that the participant remained on the medication was 31.5 weeks (SD 14.6, minimum 8.7 and maximum 52). There were no serious adverse events considered to be related to the trial. Interpretation: This is the first trial to show that it is safe to conduct a head-to-head clinical trial comparing psychological intervention with antipsychotics and the combination in people in young people with a first-episode psychosis. However, feasibility is unclear due to not meeting the recruitment progression criteria, so amendments to trial design are required in order to conduct an adequately powered clinical and cost effectiveness trial to provide robust evidence