Malawi's mental health service

No Abstrac

Dark matter annihilation and decay in dwarf spheroidal galaxies: The classical and ultrafaint dSphs

Dwarf spheroidal (dSph) galaxies are prime targets for present and future gamma-ray telescopes hunting for indirect signals of particle dark matter. The interpretation of the data requires careful assessment of their dark matter content in order to derive robust constraints on candidate relic particles. Here, we use an optimised spherical Jeans analysis to reconstruct the `astrophysical factor' for both annihilating and decaying dark matter in 21 known dSphs. Improvements with respect to previous works are: (i) the use of more flexible luminosity and anisotropy profiles to minimise biases, (ii) the use of weak priors tailored on extensive sets of contamination-free mock data to improve the confidence intervals, (iii) systematic cross-checks of binned and unbinned analyses on mock and real data, and (iv) the use of mock data including stellar contamination to test the impact on reconstructed signals. Our analysis provides updated values for the dark matter content of 8 `classical' and 13 `ultrafaint' dSphs, with the quoted uncertainties directly linked to the sample size; the more flexible parametrisation we use results in changes compared to previous calculations. This translates into our ranking of potentially-brightest and most robust targets---viz., Ursa Minor, Draco, Sculptor---, and of the more promising, but uncertain targets---viz., Ursa Major 2, Coma---for annihilating dark matter. Our analysis of Segue 1 is extremely sensitive to whether we include or exclude a few marginal member stars, making this target one of the most uncertain. Our analysis illustrates challenges that will need to be addressed when inferring the dark matter content of new `ultrafaint' satellites that are beginning to be discovered in southern sky surveys.Comment: 19 pages, 14 figures, submitted to MNRAS. Supplementary material available on reques

JAK inhibitors: a potential treatment for JDM in the context of the role of interferon-driven pathology

Juvenile Idiopathic Inflammatory Myopathies (IIM) are a group of rare diseases that are heterogeneous in terms of pathology that can include proximal muscle weakness, associated skin changes and systemic involvement. Despite options for treatment, many patients continue to suffer resistant disease and lasting side-effects. Advances in the understanding of the immunopathology and genetics underlying IIM may specify new therapeutic targets, particularly where conventional treatment has not achieved a clinical response. An upregulated type I interferon signature is strongly associated with disease and could be a prime target for developing more specific therapeutics. There are multiple components of the IFN pathway that could be targeted for blockade therapy.Downstream of the cytokine receptor complexes are the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, which consists of JAK1-3, TYK2, and STAT1-6. Therapeutic inhibitors have been developed to target components of this pathway. Promising results have been observed in case studies reporting the use of the JAK inhibitors, Baricitinib, Tofacitinib and Ruxolitinib in the treatment of refractory Juvenile Dermatomyositis (JDM). There is still the question of safety and efficacy for the use of JAK inhibitors in JDM that need to be addressed by clinical trials. Here we review the future for the use of JAK inhibitors as a treatment for JDM

Diverse Epidemiology of Leptospira Serovars Notified in New Zealand, 1999-2017

(c) The Author/sPublishe

Adiposity, obesity, and arterial aging: longitudinal study of aortic stiffness in the Whitehall II cohort

We sought to determine whether adiposity in later midlife is an independent predictor of accelerated stiffening of the aorta. Whitehall II study participants (3789 men; 1383 women) underwent carotid-femoral applanation tonometry at the mean age of 66 and again 4 years later. General adiposity by body mass index, central adiposity by waist circumference and waist:hip ratio, and fat mass percent by body impedance were assessed 5 years before and at baseline. In linear mixed models adjusted for age, sex, ethnicity, and mean arterial pressure, all adiposity measures were associated with aortic stiffening measured as increase in pulse wave velocity (PWV) between baseline and follow-up. The associations were similar in the metabolically healthy and unhealthy, according to Adult Treatment Panel-III criteria excluding waist circumference. C-reactive protein and interleukin-6 levels accounted for part of the longitudinal association between adiposity and PWV change. Adjusting for chronic disease, antihypertensive medication and risk factors, standardized effects of general and central adiposity and fat mass percent on PWV increase (m/s) were similar (0.14, 95% confidence interval: 0.05-0.24, P=0.003; 0.17, 0.08-0.27, P<0.001; 0.14, 0.05-0.22, P=0.002, respectively). Previous adiposity was associated with aortic stiffening independent of change in adiposity, glycaemia, and lipid levels across PWV assessments. We estimated that the body mass index-linked PWV increase will account for 12% of the projected increase in cardiovascular risk because of high body mass index. General and central adiposity in later midlife were strong independent predictors of aortic stiffening. Our findings suggest that adiposity is an important and potentially modifiable determinant of arterial aging

Mycobacterium tuberculosis cords within lymphatic endothelial cells to evade host immunity

The ability of Mycobacterium tuberculosis to form serpentine cords is intrinsically related to its virulence, but specifically how M. tuberculosis cording contributes to pathogenesis remains obscure. Here, we show that several M. tuberculosis clinical isolates form intracellular cords in primary human lymphatic endothelial cells (hLECs) in vitro and in the lymph nodes of patients with tuberculosis. We identified via RNA-Seq a transcriptional program that activated, in infected-hLECs, cell survival and cytosolic surveillance of pathogens pathways. Consistent with this, cytosolic access was required for intracellular M. tuberculosis cording. Mycobacteria lacking ESX-1 type VII secretion system or phthiocerol dimycocerosates expression, which failed to access the cytosol, were indeed unable to form cords within hLECs. Finally, we show that M. tuberculosis cording is a size-dependent mechanism used by the pathogen to avoid its recognition by cytosolic sensors and evade either resting or IFN-γ–induced hLEC immunity. These results explain the long-standing association between M. tuberculosis cording and virulence and how virulent mycobacteria use intracellular cording as strategy to successfully adapt and persist in the lymphatic tracts

The epigenetic impacts of social stress: how does social adversity become biologically embedded?

Epigenetic mechanisms are implicated in the processes through which social stressors erode health in humans and other animals. Here I review progress in elucidating the biological pathways underlying the social gradient in health, with particular emphasis on how behavioral stresses influence epigenomic variation linked to health. The evidence that epigenetic changes are involved in embedding of social status-linked chronic stress is reviewed in the context of current knowledge about behavior within animal dominance hierarchies and the impacts of social position on behaviors that affect health. The roles of epigenetic mechanisms in responses to trauma and the evidence for their involvement in intergenerational transmission of the biological impacts of traumatic stress are also considered. Taken together, the emerging insights have important implications for development of strategies to improve societal health and well-being

WHO collaborative study to assess the suitability of the 1st International Standard and the 1st International Reference Panel for antibodies to Ebola virus

A WHO international collaborative study was undertaken to evaluate preparations of Ebola virus disease (EVD) convalescent plasmas for their suitability to serve as the WHO 1st International Standard (IS) and the WHO 1st International Reference Panel (IRP) for Ebola virus antibodies for use in the standardization and control of assays. The study involved participants testing the convalescent plasma sample preparations and additional monoclonal antibody samples in a blinded manner alongside the WHO International Reference Reagent (NIBSC code 15/220) using anti-EBOV assays established in their laboratories. The candidate 1st IS for Ebola virus antibodies (study sample code 92, NIBSC 15/262) consists of ampoules containing the freeze-dried equivalent of 0.5 mL pooled convalescent plasma obtained from six Sierra Leone patients recovered from EVD. The candidate 1st IRP of anti-Ebola virus convalescent plasmas (NIBSC 16/344) consists of freeze-dried preparations of single donations of convalescent plasma obtained from four patients and one healthy blood donor. Each panel member is an ampoule containing the equivalent of 0.25mL plasma. All convalescent plasmas are confirmed PCR-negative for Ebola virus and underwent, along with the negative plasma, solvent detergent (SD) treatment prior to their development into candidate WHO biological reference materials. In this collaborative study, 17 laboratories from 4 countries used a range of live Ebola virus neutralization assays, pseudotyped virus neutralisation assays and enzyme immunoassays to test the collaborative study samples. Surface plasmon resonance and Western blot assessments were also undertaken. The study found that the candidate International Standard has the highest absolute titre among the convalescent plasma samples, although the geometric mean titres of all the convalescent plasmas fall within ~5-fold of each other. The potencies of three of the convalescent samples fall near the detection limit of some assays. This study also demonstrated that the agreement between laboratories for potencies relative to the candidate International Standard represents an improvement compared to the agreement in absolute titres; however, there is poor agreement between relative potencies for some assays. The results obtained from accelerated thermal degradation studies at 1year indicate that the candidate IS is stable and suitable for long-term use. The results of the collaborative study indicate the suitability of the candidates to serve as WHO reference materials and it is proposed that 15/262 is established as the WHO 1st IS for EBOV antibodies with an assigned potency of 1.5 IU/mL when reconstituted as directed in the instructions for use. It is also proposed that 16/344 is established as the WHO 1st IRP of anti-EBOV convalescent plasmas with panel member code 95 (NIBSC 15/280) assigned a unitage of 1.1 IU/mL when reconstituted as directed in the instructions for use. The other panel members have not been assigned a unitage. The implementation and use by laboratories of the proposed WHO reference materials for EBOV antibodies will facilitate the characterization of the factors that contribute to assay variability and standardization of results across assays and laboratorie

Education, sense of mastery and mental health: results from a nation wide health monitoring study in Norway

<p>Abstract</p> <p>Background</p> <p>Earlier studies have shown that people with low level of education have increased rates of mental health problems. The aim of the present study is to investigate the association between level of education and psychological distress, and to explore to which extent the association is mediated by sense of mastery, and social variables like social support, negative life events, household income, employment and marital status.</p> <p>Methods</p> <p>The data for the study were obtained from the Level of Living Survey conducted by Statistics Norway in 2002. Data on psychological distress and psychosocial variables were gathered by a self-administered questionnaire, whereas socio-demographic data were based on register statistics. Psychological distress was measured by Hopkins Symptom Checklist 25 items.</p> <p>Results</p> <p>There was a significant association between low level of education and psychological distress in both genders, the association being strongest in women aged 55–67 years. Low level of education was also significantly associated with low sense of mastery, low social support, many negative life events (only in men), low household income and unemployment,. Sense of mastery emerged as a strong mediating variable between level of education and psychological distress, whereas the other variables played a minor role when adjusting for sense of mastery.</p> <p>Conclusion</p> <p>Low sense of mastery seems to account for much of the association between low educational level and psychological distress, and should be an important target in mental health promotion for groups with low level of education.</p

Household item ownership and self-rated health: material and psychosocial explanations

BACKGROUND: There has been an ongoing debate whether the effects of socioeconomic factors on health are due to absolute poverty and material factors or to relative deprivation and psychosocial factors. In the present analyses, we examined the importance for health of material factors, which may have a direct effect on health, and of those that may affect health indirectly, through psychosocial mechanisms. METHODS: Random national samples of men and women in Hungary (n = 973) and Poland (n = 1141) were interviewed (response rates 58% and 59%, respectively). The subjects reported their self-rated health, socioeconomic circumstances, including ownership of different household items, and perceived control over life. Household items were categorised as "basic needs", "socially oriented", and "luxury". We examined the association between the ownership of different groups of items and self-rated health. Since the lists of household items were different in Hungary and Poland, we conducted parallel identical analyses of the Hungarian and Polish data. RESULTS: The overall prevalence of poor or very poor health was 13% in Poland and 25% in Hungary. Education, material deprivation and the number of household items were all associated with poor health in bivariate analyses. All three groups of household items were positively related to self-rated health in age-adjusted analyses. The relation of basic needs items to poor health disappeared after controlling for other socioeconomic variables (mainly material deprivation). The relation of socially oriented and luxury items to poor health, however, persisted in multivariate models. The results were similar in both datasets. CONCLUSIONS: These data suggest that health is influenced by both material and psychosocial aspects of socioeconomic factors