Investigating the perception of emotion portrayed through body movements in Motor Neuron Disease

Objectives: Motor Neuron Disease (MND) disrupts signals between the brain and the muscles causing physical disability and speech difficulties. Recent studies suggest that Theory of Mind (ToM), or the ability to interpret facial expressions and empathise with others’ emotions, can be impaired by MND. Research has, however, not yet investigated whether MND causes deficits in understanding emotion portrayed by body movements. The current study used a novel computerised assessment tool, E-Motion, which was developed with the aim of assessing the ability to interpret emotions through body movements. The primary hypothesis was that individuals with MND would be impaired compared to control participants on the E-Motion test. Methods: Fifteen individuals with MND and fifteen neurotypical participants were recruited via an MND patient register and opportunity sampling. Participants completed cognitive and psychological assessments and ToM assessments: a subtest of the Awareness of Social Inference Test (TASIT), the Edinburgh Cognitive and Behavioural ALS Screen social cognition test (ECAS) and the E-Motion assessment. Results: A Mann-Whitney U Test indicated that the MND group performed significantly poorer on the E-Motion test with a large effect size (p<0.01, Eta squared=0.35, 90% CI [0.14, 0.59]) and on the ECAS social cognition subtest, with a medium effect size (p=0.02, Eta squared=0.19, 90% CI [0.02, 0.41]) compared to controls. An independent t-test indicated that the MND group attained lower scores on the TASIT subtest compared to controls with a medium effect size, although group differences were not significant (p=0.17, d=0.51, CI[-0.21,1.24]). Conclusions: Although the E-Motion results suggest possible MND-associated deficits in understanding body language, interpreting data from this task is significantly limited because the E-Motion task has not yet been formally validated. In particular, the E-Motion task requires formal development and validation studies. These studies would be required to quantify its performance across internal, external and content validity metrics to allow firmer conclusions to made. Findings from the E-Motion task should not be over-interpreted, and should be regarded as provisional and exploratory. Further research on tool development and replicating findings will be needed to advance the evidence-base in this area. The results of the validated ECAS social cognition test suggest that some individuals with MND may develop difficulties in understanding the emotions of others. This finding is in accordance with previous research in this area. Further research in larger sample sizes and subtypes of MND are required to ascertain whether ToM deficits are prevalent in the wider MND population

Plague Dot Text:Text mining and annotation of outbreak reports of the Third Plague Pandemic (1894-1952)

The design of models that govern diseases in population is commonly built on information and data gathered from past outbreaks. However, epidemic outbreaks are never captured in statistical data alone but are communicated by narratives, supported by empirical observations. Outbreak reports discuss correlations between populations, locations and the disease to infer insights into causes, vectors and potential interventions. The problem with these narratives is usually the lack of consistent structure or strong conventions, which prohibit their formal analysis in larger corpora. Our interdisciplinary research investigates more than 100 reports from the third plague pandemic (1894-1952) evaluating ways of building a corpus to extract and structure this narrative information through text mining and manual annotation. In this paper we discuss the progress of our ongoing exploratory project, how we enhance optical character recognition (OCR) methods to improve text capture, our approach to structure the narratives and identify relevant entities in the reports. The structured corpus is made available via Solr enabling search and analysis across the whole collection for future research dedicated, for example, to the identification of concepts. We show preliminary visualisations of the characteristics of causation and differences with respect to gender as a result of syntactic-category-dependent corpus statistics. Our goal is to develop structured accounts of some of the most significant concepts that were used to understand the epidemiology of the third plague pandemic around the globe. The corpus enables researchers to analyse the reports collectively allowing for deep insights into the global epidemiological consideration of plague in the early twentieth century.Comment: Journal of Data Mining & Digital Humanities 202

The MindfulBreather: Motion Guided Mindfulness.

For millennia, humans have focused their attention on the breath to develop mindfulness, but finding a scientific way to harness mindful breathing has proven elusive. Existing attempts to objectively measure and feedback on mindfulness have relied on specialist external hardware including electroencephalograms or respirometers that have been impractical for the majority of people learning to meditate. Consequently, training in the key skill of breath-awareness has lacked practical objective measures and guidance to enhance training. Here, we provide a brief technology report on an invention, The MindfulBreather® that addresses these issues. The technology is available to download embedded in a smartphone app that targets, measures and feedbacks on mindfulness of breathing in realtime to enhance training. The current article outlines only the technological concept with future studies quantifying efficacy, validity and reliability to be reported elsewhere. The MindfulBreather works by generating Motion Guided Mindfulness through interacting gyroscopic and touchscreen sensors in a three phase process: Mindfulness Induction (Phase I) gives standardized instruction to users to place their smartphone on their abdomen, breathe mindfully and to tap only at the peak of their inhalation. The smartphone's gyroscope detects periodic tilts during breathing to generate sinusoidal waveforms. Waveform-tap patterns are analyzed to determine whether the user is mindfully tapping only at the correct phase of the breathing cycle, indicating psychobiological synchronization. Mindfulness Maintenance (Phase II) provides reinforcing pleasant feedback sounds each time a breath is mindfully tapped at the right time, and the App records a mindful breath. Lastly, data-driven Insights are fed back to the user (Phase III), including the number of mindful breaths tapped and breathing rate reductions associated with parasympathetic engagement during meditation. The new MGM technology is then evaluated and contrasted with traditional mindfulness approaches and a novel Psychobiological Synchronization Model is proposed. In summary, unlike existing technology, the MindfulBreather requires no external hardware and repurposes regular smartphones to deliver app-embedded Motion-Guided Mindfulness. Technological applications include reducing mindwandering and down-regulation of the brain's default mode through enhanced mindful awareness. By objectively harnessing breath awareness, The MindfulBreather aims to realize the ancient human endeavor of mindfulness for the 21st century

Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease.

Funder: Government Department of BusinessFunder: Energy and Industrial Strategy (BEIS)Funder: Vice-Chancellor Fellowship from the University of BristolFunder: Shanghai Thousand Talents ProgramFunder: Academy of Medical Sciences (AMS) Springboard AwardFunder: BBSRC Innovation fellowshipFunder: NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of BristolBACKGROUND: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization. METHODS: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of 25 kg/m2. CONCLUSIONS: Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.This research has been conducted using the UK Biobank resource under Application Numbers ‘40135’ and ‘15825’. J.Z. is funded by a Vice-Chancellor Fellowship from the University of Bristol. This research was also funded by the UK Medical Research Council Integrative Epidemiology Unit [MC_UU_00011/1, MC_UU_00011/4 and MC_UU_00011/7]. J.Z. is supported by the Academy of Medical Sciences (AMS) Springboard Award, the Wellcome Trust, the Government Department of Business, Energy and Industrial Strategy (BEIS), the British Heart Foundation and Diabetes UK [SBF006\1117]. This study was funded/supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (G.D.S., T.R.G. and R.E.W.). This study received funding from the UK Medical Research Council [MR/R013942/1]. J.Z., Y.M.Z. and T.R.G are funded by a BBSRC Innovation fellowship. J.Z. is supported by the Shanghai Thousand Talents Program. Y.M.Z. is supported by the National Natural Science Foundation of China [81800636]. H.Z. is supported by the Training Program of the Major Research Plan of the National Natural Science Foundation of China [91642120], a grant from the Science and Technology Project of Beijing, China [D18110700010000] and the University of Michigan Health System–Peking University Health Science Center Joint Institute for Translational and Clinical Research [BMU2017JI007]. N.F. is supported by the National Institutes of Health awards R01-MD012765, R01-DK117445 and R21-HL140385. R.C. is funded by a Wellcome Trust GW4 Clinical Academic Training Fellowship [WT 212557/Z/18/Z]. The Trøndelag Health Study (the HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority and the Norwegian Institute of Public Health. M.C.B. is supported by the UK Medical Research Council (MRC) Skills Development Fellowship [MR/P014054/1]. S.F. is supported by a Wellcome Trust PhD studentship [WT108902/Z/15/Z]. Q.Y. is funded by a China Scholarship Council PhD scholarship [CSC201808060273]. Y.C. was supported by the National Key R&D Program of China [2016YFC0900500, 2016YFC0900501 and 2016YFC0900504]. The China Kadoorie Biobank baseline survey and the first resurvey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust [202922/Z/16/Z, 088158/Z/09/Z and 104085/Z/14/Z]. Japan-Kidney-Biobank was supported by AMED under Grant Number 20km0405210. P.C.H. is supported by Cancer Research UK [grant number: C18281/A19169]. A.K. was supported by DFG KO 3598/5–1. N.F. is supported by NIH awards R01-DK117445, R01-MD012765 and R21-HL140385. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk