Antidepressant use and risk of self-harm among people aged 40 years or older: A population-based cohort and self-controlled case series study

Background: Studies on the association between antidepressants and self-harm in adults were mostly conducted over a decade ago and have inconsistent findings. We aimed to compare self-harm risks by antidepressant classes among people aged 40 years or older with depression. Methods: Individuals aged ≥40 years with depression who initiated antidepressant treatment between 2001 and 2015 were retrieved from the Hong Kong Clinical Data Analysis & Reporting system, and were followed up until December 31, 2016. We conducted self-controlled case series (SCCS) analyses to estimate the incidence rate ratio (IRR) of self-harm comparing the pre-exposure (90 days before the first antidepressant use), index exposure (the first antidepressant use), and subsequent exposure (subsequent antidepressant use) periods to nonexposed periods. We applied Cox proportional hazard regressions to estimate the hazard ratio (HR) of self-harm comparing five antidepressant classes (tricyclic and related antidepressant drugs [TCAs], selective serotonin reuptake inhibitors [SSRIs], noradrenergic and specific serotonergic antidepressants [NaSSAs], serotonin–norepinephrine reuptake inhibitors [SNRIs], and others). Findings: A total of 48,724 individuals were identified. SCCS analyses (N = 3,846) found that the increased self-harm risk occurred during the pre-exposure (IRR: 22.24; 95% CI, 20.25-24.42), index exposure (7.03; 6.34-7.80), and subsequent exposure periods (2.47; 2.18-2.79) compared to the unexposed period. Cohort analyses (N = 48,724) found an association of higher self-harm risks in short-term (one year) for NaSSAs vs. TCAs (HR, 2.13; 95% CI, 1.53-2.96), SNRIs vs. TCAs (1.64; 1.01-2.68), and NaSSAs vs. SSRIs (1.75; 1.29-2.36) in the 40-64 years group. The higher risk remained significant in long-term (> one year) for NaSSAs vs. TCAs (1.55; 1.26-1.91) and NaSSAs vs. SSRIs (1.53; 1.26-1.87). In the 65+ group, only short-term differences were observed (SSRIs vs. TCAs [1.31; 1.03-1.66], SNRIs vs. SSRIs [0.44; 0.22-0.87], and SNRIs vs. NaSSAs [0.43; 0.21-0.87]). Interpretation: Within-person comparisons did not suggest that antidepressant exposure is causally associated with an increased risk of self-harm in people with depression. Between-person comparisons revealed differences in self-harm risks between certain pairs of antidepressant classes. These findings may inform clinicians’ benefit-risk assessments when prescribing antidepressants

Bayesian astrostatistics: a backward look to the future

This perspective chapter briefly surveys: (1) past growth in the use of Bayesian methods in astrophysics; (2) current misconceptions about both frequentist and Bayesian statistical inference that hinder wider adoption of Bayesian methods by astronomers; and (3) multilevel (hierarchical) Bayesian modeling as a major future direction for research in Bayesian astrostatistics, exemplified in part by presentations at the first ISI invited session on astrostatistics, commemorated in this volume. It closes with an intentionally provocative recommendation for astronomical survey data reporting, motivated by the multilevel Bayesian perspective on modeling cosmic populations: that astronomers cease producing catalogs of estimated fluxes and other source properties from surveys. Instead, summaries of likelihood functions (or marginal likelihood functions) for source properties should be reported (not posterior probability density functions), including nontrivial summaries (not simply upper limits) for candidate objects that do not pass traditional detection thresholds.Comment: 27 pp, 4 figures. A lightly revised version of a chapter in "Astrostatistical Challenges for the New Astronomy" (Joseph M. Hilbe, ed., Springer, New York, forthcoming in 2012), the inaugural volume for the Springer Series in Astrostatistics. Version 2 has minor clarifications and an additional referenc

Crystallite size-modulated exciton emission in SnO₂ nanocrystalline films grown by sputtering

Author name used in this publication: Pan, Shu Sheng.Author name used in this publication: Yu, Siu Fung.2012-2013 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach.

BACKGROUND: Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene-environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene-environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health. METHODS: We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene-environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions. FINDINGS: Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24-1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene-environment correlation but did not show the absence of passive gene-environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration). INTERPRETATION: Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment. Family-based analyses point to a role of active and reactive gene-environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects. FUNDING: Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre.This work was supported by the Wellcome Trust (Grant refs: 214322/Z/18/Z, 104036/Z/14/Z, 204623/Z/16/Z, and 217065/Z/19/Z). VW was funded by the Bowring Research Fellowship from St. Catharine’s College, Cambridge and Wellcome Trust Collaborative Award (Grant Ref: 214322/Z/18/Z). ASFK and AM are supported by Wellcome Trust Grant 104036/Z/14/Z. ASFK is also supported by an ESRC Postdoctoral Fellowship (Grant ref: ES/V011650/1). ML is supported by the scholarship from the China Scholarship Council (No. 201706990036). The work of CC has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No 707404 and grant agreement No 848158 (EarlyCause Project). MHvIJ is supported by the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development) and by a Spinoza Prize of the Netherlands Organization for Scientific Research. HMS and MRM are supported by the Medical Research Council and the University of Bristol (MC_UU_00011/7) and by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol. HMS is also supported by the European Research Council (Grant ref: 758813 MHINT). CMN is supported by the National Institute for Mental Health NIMH R01MH106595 and the Center of Excellence for Stress and Mental Health (CESAMH), Veterans Affairs San Diego. AJG and SB are supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204623/Z/16/Z). TMM and RB are supported by the NIMH (R01MH117014, TMM; K23MH120437, RB).The research was conducted in association with the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, and the NIHR Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. This research was possible due to two applications to the UK Biobank: Projects 20904 and 23787. This research was co-funded by the NIHR Cambridge Biomedical Research Centre and a Marmaduke Sheild grant. The UK Medical Research Council and Wellcome (Grant Ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The study website contains details of all data available through a fully searchable data dictionary (http://www.bristol.ac.uk/alspac/researchers/our-data/). Part of this data was collected using REDCap, see the REDCap website for details https://projectredcap.org/resources/citations/). The first phase of the Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam; the Erasmus University Rotterdam; ZonMw; the Netherlands Organization for Scientific Research (NWO); and the Ministry of Health, Welfare and Sport. The authors gratefully acknowledge the contribution of all children and parents, general practitioners, hospitals, midwives and pharmacies involved in the Generation R Study. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Erasmus School of Social and Behavioural Sciences at Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare Foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam

Frequency and predictors of the lupus low disease activity state in a multi-national and multi-ethnic cohort

published_or_final_versio

The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases

Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Assis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Gomes Araújo, Flávio M.. Fundación Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. Fundación Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Oliveira, Guilherme. Instituto Tecnológico Vale; Brasil. Fundación Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin