Primary group size, social support, gender and future mental health status in a prospective study of people living in private households throughout Great Britain

Background. Structural characteristics of social networks such as primary group size have received less attention than measures of perceived social support. Previous research suggests that associations between social network size and later common mental disorder status may differ according to sex and initial mental state. Method. Adults participating in the 2000 British National Household Survey of psychiatric morbidity were randomly selected for follow-up 18 months later. The revised Clinical Interview Schedule (CIS-R) and the Interview Measure of Social Relations (IMSR) were administered at baseline and follow-up. Primary group size was defined as the total number of close relatives and friends. A four-level scale of common mental disorder was modelled with ordinal logistic regression, based on weighted data (n=2413). Findings. After adjusting for confounders, a primary group size of three or less at time 1 predicted worse mental health at time 2. This effect was greatest in men who were initially non-cases at baseline (averaged odds 4.5) and in women who were initially cases at baseline (average odds 2.9). Primary group size at time 2 was significantly predicted by level of common mental disorder at time 1 in women but not in men. Thus, confounding by baseline disorder does not explain risk of developing poor mental health in socially isolated men. Conclusion. This study replicates the strong effects of primary group size on future mental health that emerge when men and women are studied separately and when subjects are categorized according to baseline mental health status

Serological evidence for non-lethal exposures of Mongolian wild birds to highly pathogenic avian influenza H5N1 virus.

Surveillance for highly pathogenic avian influenza viruses (HPAIV) in wild birds is logistically demanding due to the very low rates of virus detection. Serological approaches may be more cost effective as they require smaller sample sizes to identify exposed populations. We hypothesized that antigenic differences between classical Eurasian H5 subtype viruses (which have low pathogenicity in chickens) and H5N1 viruses of the Goose/Guangdong/96 H5 lineage (which are HPAIV) may be used to differentiate populations where HPAIVs have been circulating, from those where they have not. To test this we performed hemagglutination inhibition assays to compare the reactivity of serum samples from wild birds in Mongolia (where HPAIV has been circulating, n = 1,832) and Europe (where HPAIV has been rare or absent, n = 497) to a panel of reference viruses including classical Eurasian H5 (of low pathogenicity), and five HPAIV H5N1 antigens of the Asian lineage A/Goose/Guangdong/1/96. Antibody titres were detected against at least one of the test antigens for 182 Mongolian serum samples (total seroprevalence of 0.10, n = 1,832, 95% adjusted Wald confidence limits of 0.09-0.11) and 25 of the European sera tested (total seroprevalence of 0.05, n = 497, 95% adjusted Wald confidence limits of 0.03-0.07). A bias in antibody titres to HPAIV antigens was found in the Mongolian sample set (22/182) that was absent in the European sera (0/25). Although the interpretation of serological data from wild birds is complicated by the possibility of exposure to multiple strains, and variability in the timing of exposure, these findings suggest that a proportion of the Mongolian population had survived exposure to HPAIV, and that serological assays may enhance the targeting of traditional HPAIV surveillance toward populations where isolation of HPAIV is more likely.Funding for this work was provided by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), and the Department of Health and Human Services under contracts HHSN266200700007C and HHSN266200700010C. Further support was provided through a doctoral training grant to MG by the Biotechnology and Biological Sciences Research Council (BB/F016786/1).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/ 10.1371/journal.pone.011356

Relaxation and overlap probability function in the spherical and mean spherical model

The problem of the equivalence of the spherical and mean spherical models, which has been thoroughly studied and understood in equilibrium, is considered anew from the dynamical point of view during the time evolution following a quench from above to below the critical temperature. It is found that there exists a crossover time $t^* \sim V^{2/d}$ such that for $t < t^*$ the two models are equivalent, while for $t > t^*$ macroscopic discrepancies arise. The relation between the off equilibrium response function and the structure of the equilibrium state, which usually holds for phase ordering systems, is found to hold for the spherical model but not for the mean spherical one. The latter model offers an explicit example of a system which is not stochastically stable.Comment: 11 pages, 1 figure, references corrected, to appear in Phys.Rev.

How much change is enough?:Evidence from a longitudinal study on depression in UK primary care

BACKGROUND: The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists. METHODS: A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a ‘global rating of change’ scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R). RESULTS: For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) −26.7 to −14.9) on the PHQ-9; 23% (95% CI −27.8 to −18.0) on the BDI-II and 26.8% (95% CI −33.5 to −20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were −1.7, −3.5 and −1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement. CONCLUSIONS: An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit. FUNDING: Funding. National Institute for Health Research

Characterization of co-circulating swine influenza A viruses in North America and the identification of a novel H1 genetic clade with antigenic significance.

Multiple genetically and antigenically distinct hemagglutinin genes of the H1 and H3 influenza A virus (IAV) subtypes co-circulate in North American swine. This diversity has evolved by repeated transmission of IAVs from humans to swine and subsequent antigenic drift in swine. To understand the evolutionary dynamics of these diverse HA lineages in North American swine, we undertook a phylogenetic analysis of 1576 H1 and 607 H3 HA gene segments, as well as 834 N1 and 1293 N2 NA gene segments, and 2126 M gene segments. These data revealed yearly co-circulation of H1N1, H1N2, and H3N2 viruses, with three HA clades representing the majority of the HA sequences: of the H1 viruses, 42% were classified as H1δ1 and 40.6% were classified as H1γ; and of the H3 viruses 53% were classified as cluster IV-A H3N2. We detected a genetically distinct minor clade consisting of 37 H1 viruses isolated between 2003 and 2013, which we classified as H1γ-2. We estimated that this clade circulated in swine since approximately 1995, but it was not detected in swine until 2003. Though this clade only represents 1.07% of swine H1 sequences reported over the past 10 years, hemagglutination inhibition (HI) assays demonstrated that representatives of this clade of viruses are antigenically distinct, and, when measured using antigenic cartography, were as many as 7 antigenic units from other H1γ viruses. Therefore vaccines against the contemporary H1γ viruses are not likely to cross-protect against γ-2 viruses. The long-term circulation of these γ-2 viruses suggests that minor populations of viruses may be underreported in the national dataset given the long branch lengths and gaps in detections. The identification of these γ-2 viruses demonstrates the need for robust surveillance to capture the full diversity IAVs in swine in the USA and the importance of antigenic drift in the diversification and emergence of new antigenic variants in swine, which complicates vaccine design.Funding was provided by USDA-ARS and USDA355 APHIS-VS by the Supplemental Appropriations Act of 2009. NSL was funded by USDA-ARS SCA agreement number 58-3625-2-103F and the EC FP7 award number 259949. TKA was funded by USDA ARS SCA agreement number 58-3625-4-070.This is the accepted manuscript. The final version is available at http://www.sciencedirect.com/science/article/pii/S0168170215000799

The effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse/recurrence: results of a randomised controlled trial (the PREVENT study)

Background: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse/recurrence. Maintenance antidepressant medication (m-ADM) for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to m-ADM. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce the risk of relapse/recurrence compared with usual care but has not yet been compared with m-ADM in a definitive trial. Objectives: To establish whether MBCT with support to taper and/or discontinue antidepressant medication (MBCT-TS) is superior to and more cost-effective than an approach of m-ADM in a primary care setting for patients with a history of recurrent depression followed up over a 2-year period in terms of preventing depressive relapse/recurrence. Secondary aims examined MBCT’s acceptability and mechanism of action. Design: Single-blind, parallel, individual randomised controlled trial. Setting: UK general practices. Participants: Adult patients with a diagnosis of recurrent depression and who were taking m-ADM. Interventions: Participants were randomised to MBCT-TS or m-ADM with stratification by centre and symptomatic status. Outcome data were collected blind to treatment allocation and the primary analysis was based on the principle of intention to treat. Process studies using quantitative and qualitative methods examined MBCT’s acceptability and mechanism of action. Main outcomes measures: The primary outcome measure was time to relapse/recurrence of depression. At each follow-up the following secondary outcomes were recorded: number of depression-free days, residual depressive symptoms, quality of life, health-related quality of life and psychiatric and medical comorbidities. Results: In total, 212 patients were randomised to MBCT-TS and 212 to m-ADM. The primary analysis did not find any evidence that MBCT-TS was superior to m-ADM in terms of the primary outcome of time to depressive relapse/recurrence over 24 months [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.67 to 1.18] or for any of the secondary outcomes. Cost-effectiveness analysis did not support the hypothesis that MBCT-TS is more cost-effective than m-ADM in terms of either relapse/recurrence or quality-adjusted life-years. In planned subgroup analyses, a significant interaction was found between treatment group and reported childhood abuse (HR 1.89, 95% CI 1.06 to 3.38), with delayed time to relapse/recurrence for MBCT-TS participants with a more abusive childhood compared with those with a less abusive history. Although changes in mindfulness were specific to MBCT (and not m-ADM), they did not predict outcome in terms of relapse/recurrence at 24 months. In terms of acceptability, the qualitative analyses suggest that many people have views about (dis)/continuing their ADM, which can serve as a facilitator or a barrier to taking part in a trial that requires either continuation for 2 years or discontinuation. Conclusions: There is no support for the hypothesis that MBCT-TS is superior to m-ADM in preventing depressive relapse/recurrence among individuals at risk for depressive relapse/recurrence. Both treatments appear to confer protection against relapse/recurrence. There is an indication that MBCT may be most indicated for individuals at greatest risk of relapse/recurrence. It is important to characterise those most at risk and carefully establish if and why MBCT may be most indicated for this group

Comparison of two modern vaccines and previous influenza infection against challenge with an equine influenza virus from the Australian 2007 outbreak

During 2007, large outbreaks of equine influenza (EI) caused by Florida sublineage Clade 1 viruses affected horse populations in Japan and Australia. The likely protection that would be provided by two modern vaccines commercially available in the European Union (an ISCOM-based and a canarypox-based vaccine) at the time of the outbreaks was determined. Vaccinated ponies were challenged with a representative outbreak isolate (A/eq/Sydney/2888-8/07) and levels of protection were compared. A group of ponies infected 18 months previously with a phylogenetically-related isolate from 2003 (A/eq/South Africa/4/03) was also challenged with the 2007 outbreak virus. After experimental infection with A/eq/Sydney/2888-8/07, unvaccinated control ponies all showed clinical signs of infection together with virus shedding. Protection achieved by both vaccination or long-term immunity induced by previous exposure to equine influenza virus (EIV) was characterised by minor signs of disease and reduced virus shedding when compared with unvaccinated control ponies. The three different methods of virus titration in embryonated hens’ eggs, EIV NP-ELISA and quantitative RT-PCR were used to monitor EIV shedding and results were compared. Though the majority of previously infected ponies had low antibody levels at the time of challenge, they demonstrated good clinical protection and limited virus shedding. In summary, we demonstrate that vaccination with current EIV vaccines would partially protect against infection with A/eq/Sydney/2888-8/07-like strains and would help to limit the spread of disease in our vaccinated horse population

Diffusion of transcription factors can drastically enhance the noise in gene expression

We study by simulation the effect of the diffusive motion of repressor molecules on the noise in mRNA and protein levels in the case of a repressed gene. We find that spatial fluctuations due to diffusion can drastically enhance the noise in gene expression. For a fixed repressor strength, the noise due to diffusion can be minimized by increasing the number of repressors or by decreasing the rate of the open complex formation. We also show that the effect of spatial fluctuations can be well described by a two-step kinetic scheme, where formation of an encounter complex by diffusion and the subsequent association reaction are treated separately. Our results also emphasize that power spectra are a highly useful tool for studying the propagation of noise through the different stages of gene expression.Comment: 15 pages, 6 figures, REVTeX