Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment: A UK Population-Based Electronic Health Records Study

Importance: Self-harm is a prominent cause of morbidity in patients with bipolar disorder and is strongly associated with suicide. There is evolving evidence that lithium use may reduce suicidal behavior, in addition to concerns that the use of anticonvulsants may increase self-harm. Information is limited about the effects of antipsychotics when used as mood stabilizer treatment. Rates of unintentional injury are poorly defined in bipolar disorder, and understanding drug associations with this outcome may shed light on mechanisms for lithium's potential antisuicidal properties through reduction in impulsive aggression. Objective: To compare rates of self-harm, unintentional injury, and suicide in patients with bipolar disorder who were prescribed lithium, valproate sodium, olanzapine, or quetiapine fumarate. Design, Setting, and Participants: This investigation was a propensity score (PS)-adjusted and PS-matched longitudinal cohort study in a nationally representative UK sample using electronic health records data collected between January 1, 1995, and December 31, 2013. Participants included all patients diagnosed as having bipolar disorder who were prescribed lithium, valproate, olanzapine, or quetiapine as maintenance mood stabilizer treatment. Main Outcomes and Measures: The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide. Results: Of the 14 396 individuals with a diagnosis of BPD, 6671 were included in the cohort, with 2148 prescribed lithium, 1670 prescribed valproate, 1477 prescribed olanzapine, and 1376 prescribed quetiapine as maintenance mood stabilizer treatment. Self-harm rates were lower in patients prescribed lithium (205; 95% CI, 175-241 per 10 000 person-years at risk [PYAR]) compared with those prescribed valproate (392; 95% CI, 334-460 per 10 000 PYAR), olanzapine (409; 95% CI, 345-483 per 10 000 PYAR), or quetiapine (582; 95% CI, 489-692 per 10 000 PYAR). This association was maintained after PS adjustment (hazard ratio [HR], 1.40; 95% CI, 1.12-1.74 for valproate, olanzapine, or quetiapine vs lithium) and PS matching (HR, 1.51; 95% CI, 1.21-1.88). After PS adjustment, unintentional injury rates were lower for lithium compared with valproate (HR, 1.32; 95% CI, 1.10-1.58) and quetiapine (HR, 1.34; 95% CI, 1.07-1.69) but not olanzapine. The suicide rate in the cohort was 14 (95% CI, 9-21) per 10 000 PYAR. Although this rate was lower in the lithium group than for other treatments, there were too few events to allow accurate estimates. Conclusions and Relevance: Patients taking lithium had reduced self-harm and unintentional injury rates. This finding augments limited trial and smaller observational study results. It supports the hypothesis that lithium use reduces impulsive aggression in addition to stabilizing mood

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

Description et évaluation d'un réseau d'épidémiosurveillance des pathologies porcines mis en place dans un district du Nord Vietnam

Background and objective: Early menarche is increasing in prevalence worldwide, prompting clinical andpublic health interest on its links with pulmonary function. We aimed to investigate the relationship betweenearly menarche and lung function in middle age.Methods: The population-based Tasmanian LongitudinalHealth Study (born 1961; n = 8583), was initiated in 1968.The 5th Decade follow-up data (mean age: 45 years)included age at menarche and complex lung function testing. The 6th Decade follow-up (age: 53 years) repeated spirometry and gas transfer factor. Multiple linear regressionand mediation analyses were performed to determine theassociation between age at menarche and adult lung function and investigate biological pathways, including the proportion mediated by adult-attained height.Results: Girls reporting an early menarche (Conclusion:Early menarche was associated withreduced adult lung function. This is the first study toinvestigate post-BD outcomes and quantify the partialrole of adult height in this association

Vaccination uptake amongst older adults from minority ethnic backgrounds: A systematic review.

BACKGROUND: Older adults from minority ethnic backgrounds are at increased risk of contracting COVID-19 and developing severe infection and have increased risk of mortality. Whilst an age-based vaccination approach prioritising older groups is being implemented worldwide, vaccine hesitancy is high amongst minority ethnic groups. METHODS AND FINDINGS: We conducted a systematic review and convergent synthesis to systematically examine perceptions of vaccinations amongst older adults from minority ethnic backgrounds. We included studies that reported on perceptions, beliefs, and attitudes towards vaccinations in older adults aged ≥65 years from a minority ethnic background. We excluded studies of vaccinations in investigation or development, studies focused on specific medical conditions, studies where ethnic background or age group was unidentifiable, systematic reviews, editorials, and conference abstracts. We searched MEDLINE, Embase, Virtual Health Library, Web of Science, Cochrane Library, medRxiv, and PROSPERO databases from inception to 15 July 2021. Risk of bias for studies was assessed using the Mixed Methods Appraisal Tool. The quality of evidence of collective outcomes was estimated using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) framework. A total of 28 eligible studies conducted between 1997 and 2020 were included in the final analysis (17 quantitative surveys, 8 focus group or interview studies, 2 mixed methods studies, and 1 case-control study). The majority were US studies in English or Spanish, except for 6 studies set in Hong Kong, 2 studies in Japan, 1 study in Brazil, and 1 multi-centre study (including China, Indonesia, Turkey, South Korea, Greece, UK, Brazil, and Nigeria). In total, 28,262 individuals with an estimated mean age of 69.8 years were included, 63.2% of whom were female. We summarised the common concepts and themes across studies and populations using a convergent synthesis analysis. Thirteen themes categorised as barriers or facilitators were identified and grouped into structural factors-healthcare provider and system related, patient related, and policy and operational-and were analysed by minority ethnic group. The main limitation of the study was the predominance of studies from the US and East Asia. CONCLUSIONS: In this systematic review, we found that factors influencing vaccination uptake involve healthcare provider and system, patient-related, and governance-level factors that are specific to the older ethnic minority community being served. The evidence included in this review is supported by high or moderate certainty and can be translated to practice and policy. A tailored, multi-level approach combining increased education, access, and culturally competent discussions with trusted healthcare professionals to address health beliefs can maximise the potential impact of widespread vaccination policies

A comparison of the sensitivity of EQ-5D, SF-6D and TTO utility values to changes in vision and perceived visual function in patients with primary open-angle glaucoma

Background: Economic viability of treatments for primary open-angle glaucoma (POAG) should be assessed objectively to prioritise health care interventions. This study aims to identify the methods for eliciting utility values (UVs) most sensitive to differences in visual field and visual functioning in patients with POAG. As a secondary objective, the dimensions of generic health-related and vision-related quality of life most affected by progressive vision loss will be identified. Methods: A total of 132 POAG patients were recruited. Three sets of utility values (EuroQoL EQ-5D, Short Form SF-6D, Time Trade Off) and a measure of perceived visual functioning from the National Eye Institute Visual Function Questionnaire (VFQ-25) were elicited during face-to-face interviews. The sensitivity of UVs to differences in the binocular visual field, visual acuity and visual functioning measures was analysed using non-parametric statistical methods. Results: Median utilities were similar across Integrated Visual Field score quartiles for EQ-5D (P = 0.08) whereas SF-6D and Time-Trade-Off UVs significantly decreased (p = 0.01 and p = 0.001, respectively). The VFQ-25 score varied across Integrated Visual Field and binocular visual acuity groups and was associated with all three UVs (P ≤ 0.001); most of its vision-specific sub-scales were associated with the vision markers. The most affected dimension was driving. A relationship with vision markers was found for the physical component of SF-36 and not for any dimension of EQ-5D. Conclusions: The Time-Trade-Off was more sensitive than EQ-5D and SF-6D to changes in vision and visual functioning associated with glaucoma progression but could not measure quality of life changes in the mildest disease stages

The sensitivity of the tropical circulation and Maritime Continent precipitation to climate model resolution

The dependence of the annual mean tropical precipitation on horizontal resolution is investigated in the atmospheric version of the Hadley Centre General Environment Model (HadGEM1). Reducing the grid spacing from about 350 km to 110 km improves the precipitation distribution in most of the tropics. In particular, characteristic dry biases over South and Southeast Asia including the Maritime Continent as well as wet biases over the western tropical oceans are reduced. The annual-mean precipitation bias is reduced by about one third over the Maritime Continent and the neighbouring ocean basins associated with it via the Walker circulation. Sensitivity experiments show that much of the improvement with resolution in the Maritime Continent region is due to the specification of better resolved surface boundary conditions (land fraction, soil and vegetation parameters) at the higher resolution. It is shown that in particular the formulation of the coastal tiling scheme may cause resolution sensitivity of the mean simulated climate. The improvement in the tropical mean precipitation in this region is not primarily associated with the better representation of orography at the higher resolution, nor with changes in the eddy transport of moisture. Sizeable sensitivity to changes in the surface fields may be one of the reasons for the large variation of the mean tropical precipitation distribution seen across climate models

The evolutionary dynamics of microRNAs in domestic mammals

MiRNAs are crucial regulators of gene expression found across both the plant and animal kingdoms. While the number of annotated miRNAs deposited in miRBase has greatly increased in recent years, few studies provided comparative analyses across sets of related species, or investigated the role of miRNAs in the evolution of gene regulation. We generated small RNA libraries across 5 mammalian species (cow, dog, horse, pig and rabbit) from 4 different tissues (brain, heart, kidney and testis). We identified 1676 miRBase and 413 novel miRNAs by manually curating the set of computational predictions obtained from miRCat and miRDeep2. Our dataset spanning five species has enabled us to investigate the molecular mechanisms and selective pressures driving the evolution of miRNAs in mammals. We highlight the important contributions of intronic sequences (366 orthogroups), duplication events (135 orthogroups) and repetitive elements (37 orthogroups) in the emergence of new miRNA loci. We use this framework to estimate the patterns of gains and losses across the phylogeny, and observe high levels of miRNA turnover. Additionally, the identification of lineage-specific losses enables the characterisation of the selective constraints acting on the associated target sites. Compared to the miRBase subset, novel miRNAs tend to be more tissue specific. 20 percent of novel orthogroups are restricted to the brain, and their target repertoires appear to be enriched for neuron activity and differentiation processes. These findings may reflect an important role for young miRNAs in the evolution of brain expression plasticity. Many seed sequences appear to be specific to either the cow or the dog. Analyses on the associated targets highlight the presence of several genes under artificial positive selection, suggesting an involvement of these miRNAs in the domestication process. Altogether, we provide an overview on the evolutionary mechanisms responsible for miRNA turnover in 5 domestic species, and their possible contribution to the evolution of gene regulation

Prescribing of antipsychotics in UK primary care: a cohort study.

To examine the recorded indication for antipsychotic prescriptions in UK primary care