Frequency of health-care utilization by adults who use illicit drugs: a systematic review and meta-analysis.

AIMS: To summarize evidence on the frequency and predictors of health-care utilization among people who use illicit drugs. DESIGN: Systematic search of MEDLINE, EMBASE and PsychINFO for observational studies reporting health-care utilization published between 1 January 2000 and 3 December 2018. We conducted narrative synthesis and meta-analysis following a registered protocol (identifier: CRD42017076525). SETTING AND PARTICIPANTS: People who use heroin, powder cocaine, crack cocaine, methamphetamine, amphetamine, ecstasy/3,4-methyl​enedioxy​methamphetamine (MDMA), cannabis, hallucinogens or novel psychoactive substances; have a diagnosis of 'substance use disorder'; or use drug treatment services. MEASUREMENTS: Primary outcomes were the cumulative incidence (risk) and rate of care episodes in three settings: primary care, hospital admissions (in-patient) and emergency department (ED). FINDINGS: Ninety-two studies were included, 84% from North America and Australia. Most studies focused on people using heroin, methamphetamine or crack cocaine, or who had a diagnosis of drug dependence. We were able to conduct a meta-analysis of rates across 25 studies reporting ED episodes and 25 reporting hospital admissions, finding pooled rates of 151 [95% confidence interval (CI) = 114-201] and 41 (95% CI = 30-57) per 100 person-years, respectively; on average 4.8 and 7.1 times more often than the general population. Heterogeneity was very high and was not explained by drugs used, country of study, recruitment setting or demographic characteristics. Predictors of health-care utilization were consistent across studies and included unstable housing, drug injection and mental health problems. Opioid substitution therapy was consistently associated with reduced ED presentation and hospital admission. There was minimal research on health-care utilization by people using ecstasy/MDMA, powder cocaine, hallucinogens or novel psychoactive substances. CONCLUSIONS: People who use illicit drugs are admitted to emergency department or hospital several times more often than the general population

A research agenda for seed-trait functional ecology

Trait-based approaches have improved our understanding of plant evolution, community assembly and ecosystem functioning. A major challenge for the upcoming decades is to understand the functions and evolution of early life-history traits, across levels of organization and ecological strategies. Although a variety of seed traits are critical for dispersal, persistence, germination timing and seedling establishment, only seed mass has been considered systematically. Here we suggest broadening the range of morphological, physiological and biochemical seed traits to add new understanding on plant niches, population dynamics and community assembly. The diversity of seed traits and functions provides an important challenge that will require international collaboration in three areas of research. First, we present a conceptual framework for a seed ecological spectrum that builds upon current understanding of plant niches. We then lay the foundation for a seed-trait functional network, the establishment of which will underpin and facilitate trait-based inferences. Finally, we anticipate novel insights and challenges associated with incorporating diverse seed traits into predictive evolutionary ecology, community ecology and applied ecology. If the community invests in standardized seed-trait collection and the implementation of rigorous databases, major strides can be made at this exciting frontier of functional ecology

DNA methylation predicts age and provides insight into exceptional longevity of bats

This work was supported by a Paul G. Allen Frontiers Group grant to S.H., the University of Maryland, College of Computer, Mathematical and Natural Sciences to G.S.W., an Irish Research Council Consolidator Laureate Award to E.C.T., a UKRI Future Leaders Fellowship (MR/T021985/1) to S.C.V. and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to P.A.F. S.C.V. and P.D. were supported by a Max Planck Research Group awarded to S.C.V. by the Max Planck Gesellschaft, and S.C.V. and E.Z.L. were supported by a Human Frontiers Science Program Grant (RGP0058/2016) awarded to S.C.V. L.J.G. was supported by an NSERC PGS-D scholarship.Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.Publisher PDFPeer reviewe

A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity

Background: The clinical attack rate of influenza is influenced by prior immunity and mixing patterns in the host population, and also by the proportion of infections that are asymptomatic. This complexity makes it difficult to directly estimate R0 from the attack rate, contributing to uncertainty in epidemiological models to guide pandemic planning. We have modelled multiple wave outbreaks of influenza from different populations to allow for changing immunity and asymptomatic infection and to make inferences about R0. \ud \ud Data and Methods. On the island of Tristan da Cunha (TdC), 96% of residents reported illness during an H3N2 outbreak in 1971, compared with only 25% of RAF personnel in military camps during the 1918 H1N1 pandemic. Monte Carlo Markov Chain (MCMC) methods were used to estimate model parameter distributions. \ud \ud Findings. We estimated that most islanders on TdC were non-immune (susceptible) before the first wave, and that almost all exposures of susceptible persons caused symptoms. The median R0 of 6.4 (95% credibility interval 3.7–10.7) implied that most islanders were exposed twice, although only a minority became ill in the second wave because of temporary protection following the first wave. In contrast, only 51% of RAF personnel were susceptible before the first wave, and only 38% of exposed susceptibles reported symptoms. R0 in this population was also lower [2.9 (2.3–4.3)], suggesting reduced viral transmission in a partially immune population. \ud \ud Interpretation: Our model implies that the RAF population was partially protected before the summer pandemic wave of 1918, arguably because of prior exposure to interpandemic influenza. Without such protection, each symptomatic case of influenza would transmit to between 2 and 10 new cases, with incidence initially doubling every 1–2 days. Containment of a novel virus could be more difficult than hitherto supposed

Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development

β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome

Standard comparison of local mental health care systems in eight European countries

Aims. There is a need of more quantitative standardised data to compare local Mental Health Systems (MHSs) across international jurisdictions. Problems related to terminological variability and commensurability in the evaluation of services hamper like-with-like comparisons and hinder the development of work in this area. This study was aimed to provide standard assessment and comparison of MHS in selected local areas in Europe, contributing to a better understanding of MHS and related allocation of resources at local level and to lessen the scarcity in standard service comparison in Europe. This study is part of the Seventh Framework programme REFINEMENT (Research on Financing Systems' Effect on the Quality of Mental Health Care in Europe) project. Methods. A total of eight study areas from European countries with different systems of care (Austria, England, Finland, France, Italy, Norway, Romania, Spain) were analysed using a standard open-access classification system (Description and Evaluation of Services for Long Term Care in Europe, DESDE-LTC). All publicly funded services universally accessible to adults (>= 18 years) with a psychiatric disorder were coded. Care availability, diversity and capacity were compared across these eight local MHS. Results. The comparison of MHS revealed more community-oriented delivery systems in the areas of England (Hampshire) and Southern European countries (Verona - Italy and Girona - Spain). Community-oriented systems with a higher proportion of hospital care were identified in Austria (Industrieviertel) and Scandinavian countries (Sor-Trondelag in Norway and Helsinki-Uusimaa in Finland), while Loiret (France) was considered as a predominantly hospital-based system. The MHS in Suceava (Romania) was still in transition to community care. Conclusions. There is a significant variation in care availability and capacity across MHS of local areas in Europe. This information is relevant for understanding the process of implementation of community-oriented mental health care in local areas. Standard comparison of care provision in local areas is important for context analysis and policy planning.Peer reviewe

Harvesting Memory, Preserving Home: A Cookbook of the Painted Turtle Farm/Cosechando Memoria, Preservando el Hogar: Un Libro de Cocina de la Granja de la Tortuga Pintada

About this Project In the fall of 2018, 14 of the families and 32 students from two first-year seminars, Crossing Borders: Immigration, Identity, and Development and Immigrant Stories, worked together to create this cookbook. Families submitted their favorite dishes and then invited students to their homes to demonstrate the preparation. As they cooked and ate together, students recorded the steps to make the recipe and listened as connections between food, memory, family, migration, traditions, and religion emerged. Harvesting Memory, Preserving Home: A Cookbook of the Painted Turtle Farm is the product of this undertaking. In it, we offer the collection of recipes as well as a short story from each family, bring meaning to the food we eat, the places life brings us, and the memories we share. Sobre este Projecto En el otoño de 2018, 12 de las familias y 32 estudiantes de dos clases, Cruzando Fronteras: Immigración, Identidad, y Desarrollo y Las Historias Immigrantes trabajaron juntos para cear este libro de cocina. Las familias escogieron platos con una importancia o una memoria especial para preparar en sus casas con los estudiantes. Durante el proceso de concinar y comer juntos, los estudiantes anotaron los pasos para preparar la receta. Ellos escucharon las conexiones entre la comida, la memoria, la familia, la migración, las tradiciones, y la religión. Cosechando Memoria, Preservando el Hogar: Un Libro de Cocina de la Granja de la Tortuga Pintada es el fruto de este proyecto. Ofrecemos la collección de recetas además de una historia breve de cada familia, para dar significado a los alimentos que comemos, los lugares donde la vida nos trae, y las memorias que nos compartimos

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text