Detecting and reducing heterogeneity of error in acoustic classification

Passive acoustic monitoring can be an effective method for monitoring species, allowing the assembly of large audio datasets, removing logistical constraints in data collection and reducing anthropogenic monitoring disturbances. However, the analysis of large acoustic datasets is challenging and fully automated machine learning processes are rarely developed or implemented in ecological field studies. One of the greatest uncertainties hindering the development of these methods is spatial generalisability—can an algorithm trained on data from one place be used elsewhere? We demonstrate that heterogeneity of error across space is a problem that could go undetected using common classification accuracy metrics. Second, we develop a method to assess the extent of heterogeneity of error in a random forest classification model for six Amazonian bird species. Finally, we propose two complementary ways to reduce heterogeneity of error, by (i) accounting for it in the thresholding process and (ii) using a secondary classifier that uses contextual data. We found that using a thresholding approach that accounted for heterogeneity of precision error reduced the coefficient of variation of the precision score from a mean of 0.61 ± 0.17 (SD) to 0.41 ± 0.25 in comparison to the initial classification with threshold selection based on F-score. The use of a secondary, contextual classification with thresholding selection accounting for heterogeneity of precision reduced it further still, to 0.16 ± 0.13, and was significantly lower than the initial classification in all but one species. Mean average precision scores increased, from 0.66 ± 0.4 for the initial classification, to 0.95 ± 0.19, a significant improvement for all species. We recommend assessing—and if necessary correcting for—heterogeneity of precision error when using automated classification on acoustic data to quantify species presence as a function of an environmental, spatial or temporal predictor variable

SleepSure: A pilot randomised controlled trial to assess the effects of eye masks and earplugs on the quality of sleep for patients in hospital

Objective. To determine the short-term effects of supplying hospital inpatients with earplugs and eye masks, preparatory to a full-scale trial. Design. A single centre open-label, two-arm, parallel group, randomised controlled trial. Setting. Thirteen medical and surgical wards in a large teaching hospital in the United Kingdom. Participants. Everyone admitted to hospital aged 18 years or older, who stayed overnight, and had the mental capacity and sufficient understanding of English to give consent, the ability to complete the study questionnaire, and the ability to use earplugs and eye masks unaided was considered. Interventions. The intervention group were provided with earplugs and eye masks for use the following night, and the control group received standard care. Main measures. Sleep quality assessed using the SleepSure questionnaire after the first night of using the intervention; use of earplugs and eye masks; number of falls throughout their inpatient stay; use of zopiclone during inpatient stay; length of stay; recruitment rate. Results.1,600 patients admitted, 626 (39%) eligible, 206 (13% total, 33% eligible) recruited (intervention group, 109). The intervention group’s mean sleep quality score was 6·33 (95% CI: 5·89 to 6·77), compared with 5·09 (95% CI 4·66 to 5·52) in the control group (p<0·001]. There were no differences in use of zopiclone, falls, or length of stay between the groups. Ninety-one (86%) of the intervention group reported using the earplugs and/or eye masks. Conclusions. The intervention seems feasible, and effective, but trial eligibility rate and rate of recruitment into the study were limited

Gestational length assignment based on last menstrual period, first trimester crown-rump length, ovulation, and implantation timing.

PURPOSE: Understanding the natural length of human pregnancy is central to clinical care. However, variability in the reference methods to assign gestational age (GA) confound our understanding of pregnancy length. Assignation from ultrasound measurement of fetal crown-rump length (CRL) has superseded that based on last menstrual period (LMP). Our aim was to estimate gestational length based on LMP, ultrasound CRL, and implantation that were known, compared to pregnancy duration assigned by day of ovulation. METHODS: Prospective study in 143 women trying to conceive. In 71 ongoing pregnancies, gestational length was estimated from LMP, CRL at 10-14 weeks, ovulation, and implantation day. For each method of GA assignment, the distribution in observed gestational length was derived and both agreement and correlation between the methods determined. RESULTS: Median ovulation and implantation days were 16 and 27, respectively. The gestational length based on LMP, CRL, implantation, and ovulation was similar: 279, 278, 276.5 and 276.5 days, respectively. The distributions for observed gestational length were widest where GA was assigned from CRL and LMP and narrowest when assigned from implantation and ovulation day. The strongest correlation for gestational length assessment was between ovulation and implantation (r = 0.98) and weakest between CRL and LMP (r = 0.88). CONCLUSIONS: The most accurate method of predicting gestational length is ovulation day, and this agrees closely with implantation day. Prediction of gestational length from CRL and known LMP are both inferior to ovulation and implantation day. This information could have important implications on the routine assignment of gestational age

IRF5 promotes influenza-induced inflammatory responses in human iPSC-derived myeloid cells and murine models.

Recognition of Influenza A virus (IAV) by the innate immune system triggers pathways that restrict viral replication, activates innate immune cells, and regulates adaptive immunity. However, excessive innate immune activation can exaggerate disease. The pathways promoting excessive activation are incompletely understood, with limited experimental models to investigate mechanisms driving influenza-induced inflammation in humans. Interferon regulatory factor (IRF5) is a transcription factor that plays important roles in induction of cytokines after viral sensing. In an in vivo model of IAV infection, IRF5 deficiency reduced IAV-driven immune pathology and associated inflammatory cytokine production, specifically reducing cytokine-producing myeloid cell populations in Irf5-/- mice, but not impacting type 1 IFN production or virus replication. Using cytometry by time-of-flight (CyTOF), we identified that human lung IRF5 expression was highest in cells of the myeloid lineage. To investigate the role of IRF5 in mediating human inflammatory responses by myeloid cells to IAV, we employed human induced pluripotent stem cells (hIPSCs) with biallelic mutations in IRF5, demonstrating for the first time iPS-derived dendritic cells (iPS-DCs) with biallelic mutations can be used to investigate regulation of human virus-induced immune responses. Using this technology, we reveal that IRF5 deficiency in human DCs, or macrophages, corresponded with reduced virus-induced inflammatory cytokine production, with IRF5 acting downstream of TLR7 and, possibly, RIG-I after viral sensing. Thus, IRF5 acts as a regulator of myeloid cell inflammatory cytokine production during IAV infection in mice and humans, and drives immune-mediated viral pathogenesis independently of type 1 IFN and virus replication.ImportanceThe inflammatory response to Influenza A virus (IAV) participates in infection control but contributes to disease severity. After viral detection intracellular pathways are activated, initiating cytokine production, but these pathways are incompletely understood. We show that interferon regulatory factor 5 (IRF5) mediates IAV-induced inflammation and, in mice, drives pathology. This was independent of antiviral type 1 IFN and virus replication, implying that IRF5 could be specifically targeted to treat influenza-induced inflammation. We show for the first time that human iPSC technology can be exploited in genetic studies of virus-induced immune responses. Using this technology, we deleted IRF5 in human myeloid cells. These IRF5-deficient cells exhibited impaired influenza-induced cytokine production and revealed that IRF5 acts downstream of Toll-like receptor 7 and possibly retinoic acid-inducible gene-I. Our data demonstrate the importance of IRF5 in influenza-induced inflammation, suggesting genetic variation in the IRF5 gene may influence host susceptibility to viral diseases.This work was supported by The Wellcome Trust. This work was funded by a Wellcome 641 Trust Senior Research Fellowship to Ian Humphreys (207503/Z/17/Z); Medical Research 642 Council, United Kingdom (MR/L018942/1 and MRC Human Immunology Unit Core); 643 Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences 644 (CIFMS), China (grant number: 2018-I2M-2-002). The Wellcome Trust Sanger Institute was 645 the source of the Kolf2 human induced pluripotent cell line which was generated under the 646 Human Induced Pluripotent Stem Cell Initiative funded by a grant from the Wellcome Trust Downloaded from http://jvi.asm.org/ on March 2, 2020 at CAMBRIDGE UNIV27 and Medical Research Council, supported 647 by the Wellcome Trust (WT098051) and the 648 NIHR/Wellcome Trust Clinical Research Facility, and Life Science Technologies 649 Corporation provided Cytotune for reprogramming. We thank the Wellcome Trust Sanger Institute Gene editing pipeline for generation of IRF5-/- 650 iPSCs and the Mass spectrometry 651 Facility at the Weatherall Institute of Molecular Medicine for help with CyTOF experiments

Cross-sectional study comparing cognitive function in treatment responsive versus treatment non-responsive schizophrenia: evidence from the STRATA study

Background 70%–84% of individuals with antipsychotic treatment resistance show non-response from the first episode. Emerging cross-sectional evidence comparing cognitive profiles in treatment resistant schizophrenia to treatment-responsive schizophrenia has indicated that verbal memory and language functions may be more impaired in treatment resistance. We sought to confirm this finding by comparing cognitive performance between antipsychotic non-responders (NR) and responders (R) using a brief cognitive battery for schizophrenia, with a primary focus on verbal tasks compared against other measures of cognition. Design Cross-sectional. Setting This cross-sectional study recruited antipsychotic treatment R and antipsychotic NR across four UK sites. Cognitive performance was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). Participants One hundred and six participants aged 18–65 years with a diagnosis of schizophrenia or schizophreniform disorder were recruited according to their treatment response, with 52 NR and 54 R cases. Outcomes Composite and subscale scores of cognitive performance on the BACS. Group (R vs NR) differences in cognitive scores were investigated using univariable and multivariable linear regressions adjusted for age, gender and illness duration. Results Univariable regression models observed no significant differences between R and NR groups on any measure of the BACS, including verbal memory (ß=−1.99, 95% CI −6.63 to 2.66, p=0.398) and verbal fluency (ß=1.23, 95% CI −2.46 to 4.91, p=0.510). This pattern of findings was consistent in multivariable models. Conclusions The lack of group difference in cognition in our sample is likely due to a lack of clinical distinction between our groups. Future investigations should aim to use machine learning methods using longitudinal first episode samples to identify responder subtypes within schizophrenia, and how cognitive factors may interact within this

Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations

Autosomal recessive mutations in the RARS2 gene encoding the mitochondrial arginyl-transfer RNA synthetase cause infantile-onset myoencephalopathy pontocerebellar hypoplasia type 6 (PCH6). We describe 2 sisters with novel compound heterozygous RARS2 mutations who presented perinatally with neurologic features typical of PCH6 but with additional features including cardiomyopathy, hydrops, and pulmonary hypoplasia and who died at 1 day and 14 days of age. Magnetic resonance imaging findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Enzyme histochemistry of postmortem tissues revealed a near-global cytochrome c oxidase-deficiency; assessment of respiratory chain enzyme activities confirmed severe deficiencies involving complexes I, III, and IV. Molecular genetic studies revealed 2 RARS2 gene mutations: a c.1A>G, p.? variant predicted to abolish the initiator methionine, and a deep intronic c.613-3927C>T variant causing skipping of exons 6–8 in the mature RARS2 transcript. Neuropathologic investigation included low brain weights, small brainstem and cerebellum, deep cerebral white matter pathology, pontine nucleus neuron loss (in 1 sibling), and peripheral nerve pathology. Mitochondrial respiratory chain immunohistochemistry in brain tissues confirmed an absence of complexes I and IV immunoreactivity with sparing of mitochondrial numbers. These cases expand the clinical spectrum of RARS2 mutations, including antenatal features and widespread mitochondrial respiratory chain deficiencies in postmortem brain tissues

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

A cluster randomised controlled trial to evaluate the impact of a gender transformative intervention on intimate partner violence against women in newly formed neighbourhood groups in Tanzania.

INTRODUCTION: Violence against women is a global public health concern; around a quarter of women will experience intimate partner physical or sexual violence during their lifetime. We assessed the impact of a gender transformative intervention for women designed to prevent intimate partner violence (IPV). METHODS: We conducted a cluster randomised controlled trial in Mwanza city, Tanzania, among women in newly formed neighbourhood groups to evaluate a 10-session participatory intervention that aims to empower women, prevent IPV and promote healthy relationships. Following a baseline interview, groups were randomly assigned (1:1 ratio) to the intervention or control arm. An intention-to-treat analysis was conducted to assess the impact of the intervention on the main outcomes, assessed 24 months postintervention. These included past-year physical IPV and sexual IPV (primary); past-year emotional abuse; and acceptability and tolerance of IPV. RESULTS: Between September 2015 and February 2017, 1265 women were recruited in 66 neighbourhoods and randomly allocated to intervention (n=627 women in 33 neighbourhoods) or control (n=638 women in 33 neighbourhoods). Assessment of outcomes was completed for 551 (88%) intervention and 575 (90%) control women. Among intervention women, 113 (21%) reported physical IPV compared with 117 (20%) control women (adjusted OR (aOR) 0.98, 95% CI 0.72 to 1.33, p=0.892), and 109 (20%) intervention women reported sexual IPV compared with 121 (21%) control women (aOR 0.98, 95% CI 0.72 to 1.32, p=0.881). Intervention women reported less emotional abuse (aOR 0.74, 95% CI 0.56 to 0.98, p=0.035), and were less likely to express attitudes accepting of IPV (aOR 0.49, 95% CI 0.36 to 0.66, p<0.001), and beliefs that IPV is a private matter (aOR 0.54, 95% CI 0.38 to 0.78, p=0.001), or should be tolerated (aOR 0.48, 95% CI 0.34 to 0.66, p<0.001). CONCLUSION: These results indicate that the intervention was effective in reducing emotional abuse and positively impacting attitudes and beliefs condoning IPV, but was not sufficient to reduce physical or sexual IPV. TRIAL REGISTRATION NUMBER: NCT02592252

A social empowerment intervention to prevent intimate partner violence against women in a microfinance scheme in Tanzania: findings from the MAISHA cluster randomised controlled trial.

BACKGROUND: Globally, about 30% of women have experienced physical or sexual violence, or both, from an intimate partner during their lifetime. Associations between poverty and women's increased risk of intimate partner violence have been observed. We therefore aimed to assess the effect of a violence prevention intervention delivered to women participating in a group-based microfinance scheme in Tanzania. METHODS: We did a cluster randomised controlled trial among women taking part in a microfinance loan scheme in Mwanza city, Tanzania. A microfinance loan group was only enrolled if at least 70% of members consented. We randomly assigned the microfinance groups in blocks of six to receive either the intervention (ie, the intervention arm) or be wait-listed for the intervention after the trial (ie, the control arm). Women in both arms of the trial met weekly for loan repayments. Only those in the intervention arm participated in the ten-session MAISHA intervention that aims to empower women and prevent intimate partner violence. Given the nature of the intervention, it was not possible to mask participants or the research team. The primary outcome was a composite of reported past-year physical or sexual intimate partner violence, or both. Secondary outcome measures were past-year physical, sexual, and emotional intimate partner violence; acceptability and tolerance of intimate partner violence; and attitudes and beliefs related to intimate partner violence. These outcomes were assessed 24 months after the intervention. An intention-to-treat analysis was done, adjusting for age, education, and baseline measure of the respective outcome. The study is registered with ClinicalTrials.gov, number NCT02592252. FINDINGS: Between September, 2014, and June, 2015, 66 (65%) of 101 microfinance groups approached in the study area met the trial eligibility criteria and were enrolled, of which 33 (n=544 women) were allocated to the intervention arm and 33 (n=505 women) to the control arm. Overall, 485 (89%) of 544 women in the intervention arm and 434 (86%) of 505 in the control arm completed the outcomes assessment. Among the intervention arm, 112 (23%) of 485 women reported past-year physical or sexual intimate partner violence, or both, compared with 119 (27%) of 434 in the control arm (adjusted odds ratio [aOR] 0·69, 95% CI 0·47-1·01; p=0·056). Women in the intervention arm were less likely to report physical intimate partner violence (aOR 0·64, 95% CI 0·41-0·99; p=0·043) and were less likely to express attitudes accepting of intimate partner violence (0·45, 0·34-0·61; p<0·0001) or beliefs that intimate partner violence is a private matter (0·51, 0·32-0·81; p=0·005) or should be tolerated (0·68, 0·45-1·01; p=0·055). There was no evidence of an effect on reported sexual or emotional intimate partner violence. There were no reports that participation in the trial had led to new episodes of violence or worsening of ongoing violence and abuse. INTERPRETATION: Reported physical or sexual intimate partner violence, or both, was reduced among women who participated in the intervention arm, although the effect was greater for physical intimate partner violence, suggesting that intimate partner violence is preventable in high-risk settings such as Tanzania. FUNDING: Anonymous donor and STRIVE Consortium

Exploring the feasibility and acceptability of integrating screening for gender-based violence into HIV counselling and testing for adolescent girls and young women in Tanzania and South Africa.

BACKGROUND: Gender-based violence (GBV) undermines HIV prevention and treatment cascades, particularly among women who report partner violence. Screening for violence during HIV testing, and prior to offering pre-exposure prophylaxis (PrEP) to HIV uninfected women, provides an opportunity to identify those at heightened HIV risk and greater potential for non-adherence or early discontinuation of PrEP. The paper describes our experience with offering integrated GBV screening and referral as part of HIV counselling and testing. This component was implemented within EMPOWER, a demonstration project offering combination HIV prevention, including daily oral PrEP, to young women in South Africa and Tanzania. METHODS: Between February 2017 and March 2018, a process evaluation was conducted to explore views, experiences and practices of stakeholders (study participants and study clinical staff) during implementation of the GBV screening component. This article assesses the feasibility and acceptability of the approach from multiple stakeholder perspectives, drawing on counselling session observations (n = 10), in-depth interviews with participants aged 16-24 (n = 39) and clinical staff (n = 13), and notes from debriefings with counsellors. Study process data were also collected (e.g. number of women screened and referred). Following a thematic inductive approach, qualitative data were analysed using qualitative software (NVivo 11). RESULTS: Findings show that 31% of young women screened positive for GBV and only 10% requested referrals. Overall, study participants accessing PrEP were amenable to being asked about violence during HIV risk assessment, as this offered the opportunity to find emotional relief and seek help, although a few found this traumatic. In both sites, the sensitive and empathetic approach of the staff helped mitigate distress of GBV disclosure. In general, the delivery of GBV screening in HCT proved to be feasible, provided that the basic principles of confidentiality, staff empathy, and absence of judgment were observed. However, uptake of linkage to further care remained low in both sites. CONCLUSION: Most stakeholders found GBV screening acceptable and feasible. Key principles that should be in place for young women to be asked safely about GBV during HIV counselling and testing included respect for confidentiality, a youth-friendly and non-judgmental environment, and a functioning referral network