A note on the use of sensitivity analysis to explore the potential impact of declining institutional care utilisation on disability prevalence

Many health and disability surveys are conducted using the non-institutionalised population as a sampling frame. Consequently, it is possible that changes in the utilisation of institutional care could account for all or part of any change in the observed prevalence of functional limitation, disability or other health state, based on samples from the non-institutionalised population. Using conditional probability arguments, I present an adjustment formula for computing health state prevalences for the non-institutionalised population under a scenario in which health state prevalences are held constant except for movement into the non-institutionalised population of individuals who would formerly have been in institutional care. By comparing the adjusted prevalence with observed non-institutionalised health state prevalences the contribution of changes in institutionalisation to observed changes in the non-institutionalised health state prevalence can be assessed

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by ~17% for every 1% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time

Supernova 2007bi as a pair-instability explosion

Stars with initial masses 10 M_{solar} < M_{initial} < 100 M_{solar} fuse progressively heavier elements in their centres, up to inert iron. The core then gravitationally collapses to a neutron star or a black hole, leading to an explosion -- an iron-core-collapse supernova (SN). In contrast, extremely massive stars (M_{initial} > 140 M_{solar}), if such exist, have oxygen cores which exceed M_{core} = 50 M_{solar}. There, high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs prior to oxygen ignition, and leads to a violent contraction that triggers a catastrophic nuclear explosion. Tremendous energies (>~ 10^{52} erg) are released, completely unbinding the star in a pair-instability SN (PISN), with no compact remnant. Transitional objects with 100 M_{solar} < M_{initial} < 140 M_{solar}, which end up as iron-core-collapse supernovae following violent mass ejections, perhaps due to short instances of the pair instability, may have been identified. However, genuine PISNe, perhaps common in the early Universe, have not been observed to date. Here, we present our discovery of SN 2007bi, a luminous, slowly evolving supernova located within a dwarf galaxy (~1% the size of the Milky Way). We measure the exploding core mass to be likely ~100 M_{solar}, in which case theory unambiguously predicts a PISN outcome. We show that >3 M_{solar} of radioactive 56Ni were synthesized, and that our observations are well fit by PISN models. A PISN explosion in the local Universe indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic limit, perhaps resulting from star formation processes similar to those that created the first stars in the Universe.Comment: Accepted version of the paper appearing in Nature, 462, 624 (2009), including all supplementary informatio

A mass accuracy sensitive probability based scoring algorithm for database searching of tandem mass spectrometry data

<p>Abstract</p> <p>Background</p> <p>Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has become one of the most used tools in mass spectrometry based proteomics. Various algorithms have since been developed to automate the process for modern high-throughput LC-MS/MS experiments.</p> <p>Results</p> <p>A probability based statistical scoring model for assessing peptide and protein matches in tandem MS database search was derived. The statistical scores in the model represent the probability that a peptide match is a random occurrence based on the number or the total abundance of matched product ions in the experimental spectrum. The model also calculates probability based scores to assess protein matches. Thus the protein scores in the model reflect the significance of protein matches and can be used to differentiate true from random protein matches.</p> <p>Conclusion</p> <p>The model is sensitive to high mass accuracy and implicitly takes mass accuracy into account during scoring. High mass accuracy will not only reduce false positives, but also improves the scores of true positive matches. The algorithm is incorporated in an automated database search program MassMatrix.</p

Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

Background: Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. the goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone.Methodology: We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-gamma ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-gamma, TNF-alpha, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-gamma responses and survived a lethal challenge given within the first 3 months following immunization. the addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro restimulation.Conclusion: Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi.National Institutes of HealthFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Millennium Institute for Gene TherapySt Louis Univ, Dept Internal Med, St Louis, MO 63103 USAUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, BrazilSt Louis Univ, Dept Mol Microbiol, St Louis, MO 63103 USAUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, BrazilNational Institutes of Health: RO1 AI040196CNPq: 420067/2005-1Web of Scienc

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Calculation of health expectancies with administrative data for North Rhine-Westphalia, a Federal State of Germany, 1999–2005

Pinheiro JP, Krämer A. Calculation of health expectancies with administrative data for North Rhine-Westphalia, a Federal State of Germany, 1999-2005. Population Health Metrics. 2009;7(1):4.OBJECTIVES: The main objectives of this study were to prove the feasibility of health expectancy analyses with regional administrative health statistics and to explore the utility of the calculated health expectancies in describing the health state of the population living in North Rhine-Westphalia, a Federal State of Germany. MATERIALS AND METHODS: Administrative population and mortality data as well as health data on disability and long-term care provided by public services were used to calculate: a) the life expectancy and b) the health expectancies Severe-Disability-Free Life Expectancy (SDFLE) and Long-Term-Care-Free Life Expectancy (LTCFLE) from 1999 to 2005. Calculations were done using the Sullivan method. RESULTS: SDFLE at birth was 69.9 years (males 66.2 and females 73.2 years) in 1999 and it increased to 71.7 years (males 68.6 and females 74.7 years) in 2005. The proportion of the SDFLE on the total life expectancy at birth was 89.8% (males 88.6 and females 90.8%) in 1999 and 90.7% (males 89.8 and females 91.4%) in 2005.LTCFLE at birth was 75.3 years (males 73.1 and females 77.5 years) in 1999 and it increased to 76.6 years (males 74.7 and females 78.6 years) in 2005. The proportion of the LTCFLE on the total life expectancy at birth was 96.8% (males 97.8 and females 96.1%) in 1999 and 96.8% (males 97.8 and females 96.2%) in 2005. DISCUSSION AND CONCLUSION: Both health expectancies indicate an improvement in the quantity as well as in the quality of healthy life for the population living in North Rhine Westphalia and therefore suggest a compression of morbidity from 1999 to 2005. The findings however have several limitations in their sensitivity, since we applied dichotomous valuations to the health states. In addition, the results are restricted to comparisons over time because the morbidity concepts do not allow for comparisons with populations other than the German one. Refined calculations with other summary measures of population health and with health data on other morbidity concepts are therefore reasonable

Bottom-up assembly of metallic germanium

Extending chip performance beyond current limits of miniaturisation requires new materials and functionalities that integrate well with the silicon platform. Germanium fits these requirements and has been proposed as a high-mobility channel material, a light emitting medium in silicon-integrated lasers, and a plasmonic conductor for bio-sensing. Common to these diverse applications is the need for homogeneous, high electron densities in three-dimensions (3D). Here we use a bottom-up approach to demonstrate the 3D assembly of atomically sharp doping profiles in germanium by a repeated stacking of two-dimensional (2D) high-density phosphorus layers. This produces high-density (1019 to 1020 cm-3) low-resistivity (10-4Ω ∙ cm) metallic germanium of precisely defined thickness, beyond the capabilities of diffusion-based doping technologies. We demonstrate that free electrons from distinct 2D dopant layers coalesce into a homogeneous 3D conductor using anisotropic quantum interference measurements, atom probe tomography, and density functional theory

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank

Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6 and the Scottish Funding Council HR03006. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z. YZ acknowledges support from China Scholarship Council. IJD is supported by the Centre for Cognitive Ageing and Cognitive Epidemiology which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). AMMcI and T-KC acknowledges support from the Dr Mortimer and Theresa Sackler Foundation. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Ethics approval for the study was given by the NHS Tayside committee on research ethics (reference 05/S1401/8)Peer reviewedPublisher PD