Exploring environmental and biological drivers of cetacean occurrence in the cross-border region of the Malin Shelf using data from a European fishery survey

Irish and Scottish waters are important habitats for cetaceans in Europe. Yet, little data is available for the region of the Malin Shelf, north of Ireland. Despite a rich species diversity, relative cetacean abundance appears low compared to hotspots documented west of Scotland and Ireland. Whether this perceived low prevalence accurately portrays an ecological discontinuity or arises from a lack of published results and low survey effort in that transborder area remains unclear. Here, we used sighting records from a multi-disciplinary fisheries survey, the Western European Shelf Pelagic Acoustic Survey (WESPAS), to explore cetacean habitat preferences over the Malin and Hebridean shelves. Northern minke whale and common dolphin occurrence was modelled within a Bayesian Additive Regression Trees (BART) framework, against selected environmental and biological variables. No correlation was observed between cetacean presence and in-situ prey biomass. Minke whales distribution was better explained by oceanography, notably proxies for frontal activity, and primary productivity. Common dolphins similarly showed preferences for shelf waters within 5-25km of fronts, but also affinities for fine substrates. Favourable habitats identified by the models were consistent with literature around the Hebrides and shed light on potentially important areas along the Islay front and north of Donegal, so far unreported due to data deficiency. Results will contribute towards informing future monitoring, strategic management and conservation efforts in this cross-border region

The Association between Parental Educational Expectations and School Functioning among Young People with Disabilities:A Longitudinal Investigation

Past research has established clear educational inequities between young people with disabilities and their peers. In part, some of these inequities may be attributed to expectations. In this study, we examined whether parental expectations were related to school functioning at high school, with school functioning broadly defined as ease and frequency of engagement in school-based activities. Using the Longitudinal Study of Australian Children ( N = 3,956; 48.9% female; 5.01% with disability), we examined parental expectations and school functioning measured at three time-points, biennially from the ages of 12 and 13 through to 16 and 17. A multigroup, parallel latent growth curve analysis revealed that high parental expectations at the first timepoint predicted steeper increases in the trajectory of school functioning over time, but only among young people with disability. Parental expectations did not significantly predict school functioning trajectories for the remainder of the sample. Subsequent multigroup analyses that compared disability characteristics revealed that learning difficulties and speech problems, in particular, were associated with lower parental expectations. These results suggest that the perceptions of parents in the lives of young people with disability are important and efforts to shape them may have long-term benefits

Recommendations for improving integration in national end-to-end flood forecasting systems: an overview of the FFIR (flooding from intense rainfall) programme

Recent surface-water and flash floods have caused millions of pounds worth of damage in the UK. These events form rapidly and are difficult to predict due to their short-lived and localised nature. The interdisciplinary Flooding From Intense Rainfall (FFIR) programme investigated the feasibility of enhancing the integration of an end-to-end forecasting system for flash and surface-water floods to help increase the lead time for warnings for these events. Here we propose developments to the integration of an operational end-to-end forecasting system based on the findings of the FFIR programme. The suggested developments include methods to improve radar-derived rainfall rates and understanding of the uncertainty in the position of intense rainfall in weather forecasts; the addition of hydraulic modelling components; and novel education techniques to help lead to effective dissemination of flood warnings. We make recommendations for future advances such as research into the propagation of uncertainty throughout the forecast chain. We further propose the creation of closer bonds to the end users to allow for an improved, integrated, end-to-end forecasting system that is easily accessible for users and end users alike, and will ultimately help mitigate the impacts of flooding from intense rainfall by informed and timely action

Navigating uncertain illness trajectories for young children with serious infectious illness: a mixed-methods modified grounded theory study

AbstractInfectious illness is the biggest cause of death in children due to a physical illness, particularly in children under five years. If mortality is to be reduced for this group of children, it is important to understand factors affecting their pathways to hospital.The aim of this study was to retrospectively identify organisational and environmental factors, and individual child, family, and professional factors affecting timing of admission to hospital for children under five years of age with a serious infectious illness (SII).MethodsAn explanatory modified grounded theory mixed methods design was used in collaboration with parents. Two stages of data collection were conducted: Stage 1, interviews with 22 parents whose child had recently been hospitalised with a SII and 14 health professionals (HPs) involved in their pre-admission trajectories; Stage 2, focus groups with 18 parents and 16 HPs with past experience of SII in young children. Constant comparative analysis generated the explanatory theory.FindingsThe core category was ‘navigating uncertain illness trajectories for young children with serious infectious illness’. Uncertainty was prevalent throughout the parents’ and HPs’ stories about their experiences of navigating social rules and overburdened health services for these children. The complexity of and lack of continuity within services, family lives, social expectations and hierarchies provided the context and conditions for children’s, often complex, illness trajectories. Parents reported powerlessness and perceived criticism leading to delayed help-seeking. Importantly, parents and professionals missed symptoms of serious illness. Risk averse services were found to refer more children to emergency departments.ConclusionsParents and professionals have difficulties recognising signs of SII in young children and can feel socially constrained from seeking help. The increased burden on services has made it more difficult for professionals to spot the seriously ill child.</jats:sec

Clinical outcomes and adverse events of bariatric surgery in adults with severe obesity in Scotland: the SCOTS observational cohort study

Background: Bariatric surgery is a common procedure worldwide for the treatment of severe obesity and associated comorbid conditions but there is a lack of evidence as to medium-term safety and effectiveness outcomes in a United Kingdom setting. Objective: To establish the clinical outcomes and adverse events of different bariatric surgical procedures, their impact on quality of life and the effect on comorbidities. Design: Prospective observational cohort study. Setting: National Health Service secondary care and private practice in Scotland, United Kingdom. Participants: Adults (age &gt;16 years) undergoing their first bariatric surgery procedure. Main outcome measures: Change in weight, hospital length of stay, readmission and reoperation rate, mortality, diabetes outcomes (HbA1c, medications), quality of life, anxiety, depression. Data sources: Patient-reported outcome measures, hospital records, national electronic health records (Scottish Morbidity Record 01, Scottish Care Information Diabetes, National Records Scotland, Prescription Information System). Results: Between December 2013 and February 2017, 548 eligible patients were approached and 445 participants were enrolled in the study. Of those, 335 had bariatric surgery and 1 withdrew from the study. Mean age was 46.0 (9.2) years, 74.7% were female and the median body mass index was 46.4 (42.4; 52.0) kg/m2. Weight was available for 128 participants at 3 years: mean change was −19.0% (±14.1) from the operation and −24.2% (±12.8) from the start of the preoperative weight-management programme. One hundred and thirty-nine (41.4%) participants were readmitted to hospital in the same or subsequent 35 months post surgery, 18 (5.4% of the operated cohort) had a reoperation or procedure considered to be related to bariatric surgery gastrointestinal complications or revisions. Fewer than five participants (&lt;2%) died during follow-up. HbA1c was available for 93/182 and diabetes medications for 139/182 participants who had type 2 diabetes prior to surgery; HbA1c mean change was −5.72 (±16.71) (p = 0.001) mmol/mol and 65.5% required no diabetes medications (p &lt; 0.001) at 3 years post surgery. Physical quality of life, available for 101/335 participants, improved in the 3 years post surgery, mean change in Rand 12-item Short Form Survey physical component score 8.32 (±8.95) (p &lt; 0.001); however, there was no change in the prevalence of anxiety or depression. Limitations: Due to low numbers of bariatric surgery procedures in Scotland, recruitment was stopped before achieving the intended 2000 participants and follow-up was reduced from 10 years to 3 years. Conclusions: Bariatric surgery is a safe and effective treatment for obesity. Patients in Scotland, UK, appear to be older and have higher body mass than international comparators, which may be due to the small number of procedures performed. Future work: Intervention studies are required to identify the optimal pre- and post surgery pathway to maximise safety and cost-effectiveness. Study registration: This study is registered as ISRCTN47072588. Funding details: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 10/42/02) and is published in full in Health Technology Assessment; Vol. 28, No. 7. See the NIHR Funding and Awards website for further award information

Prevalence and prognostic impact of subclinical cardiovascular disease in individuals with the metabolic syndrome and diabetes

Dostępne dane dotyczące występowania i znaczenia prognostycznego subklinicznej postaci choroby sercowo-naczyniowej (CVD), u pacjentów z zespołem metabolicznym są ograniczone. W prezentowanej pracy zbadano częstość występowania subklinicznej choroby sercowo-naczyniowej u 1945 uczestników próby Framingham Offspring Study (śr. wieku 58 lat, 59% uczestników stanowiły kobiety) z wykorzystaniem elektrokardiografii, echokardiografii, ultra ultrasonografii tętnic szyjnych, wskaźnika ciśnienia tętniczego kostka&#8211;ramię oraz wydalania albumin z moczem. W pracy oceniono w sposób prospektywny częstość występowania subklinicznej choroby sercowo-naczyniowej związanej z zespołem metabolicznym i cukrzycą, w zależności od obecności subklinicznej postaci tego schorzenia lub jej braku. Przekrojowo u 51% z 581 uczestników z zespołem metabolicznym zdiagnozowano subkliniczną formę choroby sercowo-naczyniowej w przynajmniej jednym z badań dodatkowych, co było częstsze niż u chorych bez zespołu metabolicznego [iloraz szans skorygowany pod względem wielu zmiennych 2,06 (95% CI: 1,67&#8211;2,55); p < 0,0001]. W trakcie dalszej obserwacji klinicznej (śr. 7,2 lat) jawna klinicznie choroba sercowo-naczyniowa rozwinęła się u 139 pacjentów, 59% tej liczby stanowiły osoby z zespołem metabolicznym (10,2%). Uogólniając, występowanie zespołu metabolicznego było związane ze zwiększonym ryzykiem występowania CVD [iloraz ryzyka skorygowany pod względem wielu zmiennych (HR, hazard ratio) 1,61 (95% CI: 1,12&#8211;2,33)]. U pacjentów z zespołem metabolicznym oraz subkliniczną postacią choroby sercowo-naczyniowej zaobserwowano zwiększone ryzyko wystąpienia jawnej klinicznie postaci choroby sercowo-naczyniowej [2,67 (1,62&#8211;4,41) w porównaniu z chorymi bez zdiagnozowanego zespołu metabolicznego, cukrzycy lub subklinicznej formy choroby sercowo-naczyniowej]. Zaobserwowano także mniejszy związek występowania zespołu metabolicznego z rozwinięciem się choroby sercowo-naczyniowej u pacjentów bez subklinicznej postaci CVD [HR 1,59 (95% CI: 0,87&#8211;2,90)]. Podobne zmniejszenie ryzyka wystąpienia choroby sercowo-naczyniowej u pacjentów bez subklinicznej postaci CVD obserwowano u chorych na cukrzycę. Występowanie subklinicznej formy CVD stanowiło istotny predyktor rozwinięcia się jawnej klinicznie choroby sercowo-naczyniowej u pacjentów bez zespołu metabolicznego lub cukrzycy [1,93 (1,15&#8211;3,24)]. W niniejszym populacyjnym badaniu osób z zespołem metabolicznym zaobserwowano częstsze występowanie subklinicznej postaci miażdżycy, co prawdopodobnie przyczynia się do wyższego ryzyka wystąpienia jawnej klinicznie postaci CVD związanej z tym schorzeniem.Data are limited regarding prevalence and prognostic significance of subclinical cardiovascular disease (CVD) in individuals with metabolic syndrome. We investigated prevalence of subclinical CVD in 1,945 Framingham Offspring Study participants (mean age 58 years; 59% women) using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressure, and urinary albumin excretion. We prospectively evaluated the incidence of CVD associated with metabolic syndrome and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with metabolic syndrome had subclinical disease in at least one test, a frequency higher than individuals without metabolic syndrome [multivariable- adjusted odds ratio 2.06 (95% CI: 1.67- 2.55); p < 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with metabolic syndrome (10.2%). Overall, metabolic syndrome was associated with increased CVD risk [multivariableadjusted hazards ratio (HR) 1.61 (95% CI: 1.12-2.33)]. Participants with metabolic syndrome and subclinical disease experienced increased risk of overt CVD [2.67 (1.62-4.41) compared with those without metabolic syndrome, diabetes, or subclinical disease], whereas the association of metabolic syndrome with CVD risk was attenuated in absence of subclinical disease [HR 1.59 (95% CI: 0.87&#8211;2.90)]. A similar attenuation of CVD risk in absence of subclinical disease was observed also for diabetes. Subclinical disease was a significant predictor of overt CVD in participants without metabolic syndrome or diabetes [1.93 (1.15-3.24)]. In our community-based sample, individuals with metabolic syndrome have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition

Factors Associated With Sexual Coercion in a Representative Sample of Men in Australian Prisons

Very little research has focused on men or prisoners as victims of sexual violence. This study provides the first population-based analysis of factors associated with sexual coercion of men in Australian prisons, and the first to use a computer-assisted telephone interview to collect this information in a prison setting. A random sample of men in New South Wales and Queensland prisons were surveyed using computer-assisted telephone interviewing. We asked participants about sexual coercion, defined as being forced or frightened into doing something sexually that was unwanted while in prison. Associations between sexual coercion in prison and sociodemographics, sexual coercion history outside of prison, and prison-related factors were examined. Logistic regression was used to estimate adjusted odds ratios in examining factors associated with sexual coercion in prisons. Of 2626 eligible men, 2000 participated. Participants identifying as non-heterosexual and those with a history of sexual coercion outside prison were found to be most at risk. Those in prison for the first time and those who had spent more than 5 years in prison ever were also more likely to report sexual coercion. Although prison policies and improving prison officer training may help address immediate safety and health concerns of those at risk, given the sensitivity of the issue and likely under-reporting to correctional staff, community-based organizations and prisoner peer-based groups arguably have a role too in providing both preventive and trauma-focused support

The effect of LRRK2 loss-of-function variants in humans

Analysis of large genomic datasets, including gnomAD, reveals that partial LRRK2 loss of function is not strongly associated with diseases, serving as an example of how human genetics can be leveraged for target validation in drug discovery. Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models of human gene inactivation and can be valuable indicators of gene function and the potential toxicity of therapeutic inhibitors targeting these genes(1,2). Gain-of-kinase-function variants in LRRK2 are known to significantly increase the risk of Parkinson's disease(3,4), suggesting that inhibition of LRRK2 kinase activity is a promising therapeutic strategy. While preclinical studies in model organisms have raised some on-target toxicity concerns(5-8), the biological consequences of LRRK2 inhibition have not been well characterized in humans. Here, we systematically analyze pLoF variants in LRRK2 observed across 141,456 individuals sequenced in the Genome Aggregation Database (gnomAD)(9), 49,960 exome-sequenced individuals from the UK Biobank and over 4 million participants in the 23andMe genotyped dataset. After stringent variant curation, we identify 1,455 individuals with high-confidence pLoF variants in LRRK2. Experimental validation of three variants, combined with previous work(10), confirmed reduced protein levels in 82.5% of our cohort. We show that heterozygous pLoF variants in LRRK2 reduce LRRK2 protein levels but that these are not strongly associated with any specific phenotype or disease state. Our results demonstrate the value of large-scale genomic databases and phenotyping of human loss-of-function carriers for target validation in drug discovery.Peer reviewe

Integration of “omics” Data and Phenotypic Data Within a Unified Extensible Multimodal Framework

Analysis of “omics” data is often a long and segmented process, encompassing multiple stages from initial data collection to processing, quality control and visualization. The cross-modal nature of recent genomic analyses renders this process challenging to both automate and standardize; consequently, users often resort to manual interventions that compromise data reliability and reproducibility. This in turn can produce multiple versions of datasets across storage systems. As a result, scientists can lose significant time and resources trying to execute and monitor their analytical workflows and encounter difficulties sharing versioned data. In 2015, the Ludmer Centre for Neuroinformatics and Mental Health at McGill University brought together expertise from the Douglas Mental Health University Institute, the Lady Davis Institute and the Montreal Neurological Institute (MNI) to form a genetics/epigenetics working group. The objectives of this working group are to: (i) design an automated and seamless process for (epi)genetic data that consolidates heterogeneous datasets into the LORIS open-source data platform; (ii) streamline data analysis; (iii) integrate results with provenance information; and (iv) facilitate structured and versioned sharing of pipelines for optimized reproducibility using high-performance computing (HPC) environments via the CBRAIN processing portal. This article outlines the resulting generalizable “omics” framework and its benefits, specifically, the ability to: (i) integrate multiple types of biological and multi-modal datasets (imaging, clinical, demographics and behavioral); (ii) automate the process of launching analysis pipelines on HPC platforms; (iii) remove the bioinformatic barriers that are inherent to this process; (iv) ensure standardization and transparent sharing of processing pipelines to improve computational consistency; (v) store results in a queryable web interface; (vi) offer visualization tools to better view the data; and (vii) provide the mechanisms to ensure usability and reproducibility. This framework for workflows facilitates brain research discovery by reducing human error through automation of analysis pipelines and seamless linking of multimodal data, allowing investigators to focus on research instead of data handling

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants