440 research outputs found

    Risk Assessment Activity Worksheet for Research Data Management

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    Adapted from Research Data Service, University of Illinois at Urbana-Champaign. “Making Data Management Manageable: A Risk Assessment Activity for Managing Research Data.” March 2017. http://hdl.handle.net/2142/95768. Four-step risk assessment for identifying and mitigating risks in managing research data. The worksheet is suitable for use in training activities, and for individual use

    Sex differences in mortality among binational cohort of people with chronic kidney disease: population based data linkage study

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    Objective To evaluate sex differences in mortality among people with kidney failure compared with the general population. Design Population based cohort study using data linkage. Setting The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which includes all patients receiving kidney replacement therapy in Australia (1980-2019) and New Zealand (1988-2019). Data were linked to national death registers to determine deaths and their causes, with additional details obtained from ANZDATA. Participants Of 82 844 people with kidney failure, 33 329 were female (40%) and 49 555 were male (60%); 49 376 deaths (20 099 in female patients; 29 277 in male patients) were recorded over a total of 536 602 person years of follow-up. Main outcome measures Relative measures of survival, including standardised mortality ratios, relative survival, and years of life lost, using general population data to account for background mortality (adjusting for country, age, sex, and year). Estimates were stratified by dialysis modality (haemodialysis or peritoneal dialysis) and for the subpopulation of kidney transplant recipients. Results Few differences in outcomes were found between male and female patients with kidney failure. However, compared with the general population, female patients with kidney failure had greater excess all cause deaths than male patients (female patients: standardised mortality ratio 11.3, 95% confidence interval 11.2 to 11.5, expected deaths 1781, observed deaths 20 099; male patients: 6.9, 6.8 to 6.9, expected deaths 4272, observed deaths 29 277). The greatest difference was observed among younger patients and those who died from cardiovascular disease. Relative survival was also consistently lower in female patients, with adjusted excess mortality 11% higher (95% confidence interval 8% to 13%). Average years of life lost was 3.6 years (95% confidence interval 3.6 to 3.7) greater in female patients with kidney failure compared with male patients across all ages. No major differences were found in mortality by sex for haemodialysis or peritoneal dialysis. Kidney transplantation reduced but did not entirely remove the sex difference in excess mortality, with similar relative survival (P=0.83) and years of life lost difference reduced to 2.3 years (95% confidence interval 2.2 to 2.3) between female and male patients. Conclusions Compared with the general population, female patients had greater excess deaths, worse relative survival, and more years of life lost than male patients, however kidney transplantation reduced these differences. Future research should investigate whether systematic differences exist in access to care and possible strategies to mitigate excess mortality among female patients

    Transcriptional adaptations following exercise in Thoroughbred horse skeletal muscle highlights molecular mechanisms that lead to muscle hypertrophy

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    <p>Abstract</p> <p>Background</p> <p>Selection for exercise-adapted phenotypes in the Thoroughbred racehorse has provided a valuable model system to understand molecular responses to exercise in skeletal muscle. Exercise stimulates immediate early molecular responses as well as delayed responses during recovery, resulting in a return to homeostasis and enabling long term adaptation. Global mRNA expression during the immediate-response period has not previously been reported in skeletal muscle following exercise in any species. Also, global gene expression changes in equine skeletal muscle following exercise have not been reported. Therefore, to identify novel genes and key regulatory pathways responsible for exercise adaptation we have used equine-specific cDNA microarrays to examine global mRNA expression in skeletal muscle from a cohort of Thoroughbred horses (<it>n = </it>8) at three time points (before exercise, immediately post-exercise, and four hours post-exercise) following a single bout of treadmill exercise.</p> <p>Results</p> <p>Skeletal muscle biopsies were taken from the <it>gluteus medius </it>before (T<sub>0</sub>), immediately after (T<sub>1</sub>) and four hours after (T<sub>2</sub>) exercise. Statistically significant differences in mRNA abundance between time points (T<sub>0 </sub><it>vs </it>T<sub>1 </sub>and T<sub>0 </sub><it>vs </it>T<sub>2</sub>) were determined using the empirical Bayes moderated <it>t</it>-test in the Bioconductor package Linear Models for Microarray Data (LIMMA) and the expression of a select panel of genes was validated using real time quantitative reverse transcription PCR (qRT-PCR). While only two genes had increased expression at T<sub>1 </sub>(<it>P </it>< 0.05), by T<sub>2 </sub>932 genes had increased (<it>P </it>< 0.05) and 562 genes had decreased expression (<it>P </it>< 0.05). Functional analysis of genes differentially expressed during the recovery phase (T<sub>2</sub>) revealed an over-representation of genes localized to the actin cytoskeleton and with functions in the MAPK signalling, focal adhesion, insulin signalling, mTOR signaling, p53 signaling and Type II diabetes mellitus pathways. At T<sub>1</sub>, using a less stringent statistical approach, we observed an over-representation of genes involved in the stress response, metabolism and intracellular signaling. These findings suggest that protein synthesis, mechanosensation and muscle remodeling contribute to skeletal muscle adaptation towards improved integrity and hypertrophy.</p> <p>Conclusions</p> <p>This is the first study to characterize global mRNA expression profiles in equine skeletal muscle using an equine-specific microarray platform. Here we reveal novel genes and mechanisms that are temporally expressed following exercise providing new knowledge about the early and late molecular responses to exercise in the equine skeletal muscle transcriptome.</p

    Misconceptions on COVID-19 Risk Among Ugandan Men: Results From a Rapid Exploratory Survey, April 2020

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    © Copyright © 2020 Kasozi, MacLeod, Ssempijja, Mahero, Matama, Musoke, Bardosh, Ssebuufu, Wakoko-Studstil, Echoru, Ayikobua, Mujinya, Nambuya, Onohuean, Zirintunda, Ekou and Welburn. Background: Transmission of COVID-19 in developing countries is expected to surpass that in developed countries; however, information on community perceptions of this new disease is scarce. The aim of the study was to identify possible misconceptions among males and females toward COVID-19 in Uganda using a rapid online survey distributed via social media. Methods: A cross-sectional survey carried out in early April 2020 was conducted with 161 Ugandans, who purposively participated in the online questionnaire that assessed understandings of COVID-19 risk and infection. Sixty-four percent of respondents were male and 36% were female. Results: We found significant divergences of opinion on gendered susceptibility to COVID-19. Most female respondents considered infection risk, symptoms, severe signs, and death to be equally distributed between genders. In contrast, male respondents believed they were more at risk of infection, severe symptoms, severe signs, and death (52.7 vs. 30.6%, RR = 1.79, 95% CI: 1.14–2.8). Most women did not share this perception and disagreed that males were at higher risk of infection (by a factor of three), symptoms (79% disagree), severe signs (71%, disagree), and death (70.2% disagree). Overall, most respondents considered children less vulnerable (OR = 1.12, 95% CI: 0.55–2.2) to COVID-19 than adults, that children present with less symptoms (OR = 1.57, 95% CI: 0.77–3.19), and that there would be less mortality in children (OR = 0.92, 95% CI: 0.41–1.88). Of female respondents, 76.4% considered mortality from COVID-19 to be different between the young and the elderly (RR = 1.7, 95% CI: 1.01–2.92) and 92.7% believed young adults would show fewer signs than the elderly, and 71.4% agreed that elderly COVID-19 patients would show more severe signs than the young (OR = 2.2, 95% CI: 1.4, 4.8). While respondents considered that all races were susceptible to the signs and symptoms of infection as well as death from COVID-19, they considered mortality would be highest among white people from Europe and the USA. Some respondents (mostly male 33/102, 32.4%) considered COVID-19 to be a “disease of whites” (30.2%). Conclusion: The WHO has identified women and children in rural communities as vulnerable persons who should be given more attention in the COVID-19 national response programs across Africa; however, our study has found that men in Uganda perceive themselves to be at greater risk and that these contradictory perceptions (including the association of COVID-19 with “the white” race) suggest an important discrepancy in the communication of who is most vulnerable and why. Further research is urgently needed to validate and expand the results of this small exploratory study

    Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study

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    Objective To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare

    Costs and Cost-Effectiveness of Training Traditional Birth Attendants to Reduce Neonatal Mortality in the Lufwanyama Neonatal Survival Study (LUNESP)

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    The Lufwanyama Neonatal Survival Project (“LUNESP”) was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness.We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011–2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as ‘conservative’ and ‘optimistic’ scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were 118,574and118,574 and 127,756, respectively, or 49,469and49,469 and 53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were 256,455and256,455 and 26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was 1,866,1,866, 591, and 3,024,andcostperDALYavertedwas3,024, and cost per DALY averted was 74, 24,and24, and 120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation.Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was ‘highly cost effective’. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care

    On the importance of blind testing in archaeological science: the example from lithic functional studies

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    YesBlind-testing is an important tool that should be used by all analytical fields as an approach for validating method. Several fields do this well outside of archaeological science. It is unfortunate that many applied methods do not have a strong underpinning built on, what should be considered necessary, blind-testing. Historically lithic microwear analysis has been subjected to such testing, the results of which stirred considerable debate. However, putting this aside, it is argued here that the tests have not been adequately exploited. Too much attention has been focused on basic results and the implications of those rather than using the tests as a powerful tool to improve the method. Here the tests are revisited and reviewed in a new light. This approach is used to highlight specific areas of methodological weakness that can be targeted by developmental research. It illustrates the value in having a large dataset of consistently designed blind-tests in method evaluation and suggests that fields such as lithic microwear analysis would greatly benefit from such testing. Opportunity is also taken to discuss recent developments in quantitative methods within lithic functional studies and how such techniques might integrate with current practices

    Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat : a prospective multicentre study

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    Acknowledgements This Europain project has received support from the Innovative Medicines Initiative (IMI) Joint Undertaking (under grant agreement number 115007), resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/20072013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies in-kind contribution (see http://www.imieuropain.org/ for details). Eli Lilly and Company United Kingdom: We would like to thank Dr Gary Gilmour for his assistance in bringing forward this publication. Karolinska Institute: A. Delaney also received funding from Ulla & Gustaf af Ugglas Foundation; EU Project FP7-Health-2013-Innovation-1602919-2. Boehringer Ingelheim: We would like to thank Stacey Gould for technical assistance.Peer reviewedPublisher PD

    Validation and Opportunities of Electrocardiographic Imaging: From Technical chievements to Clinical Applications

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    [EN] Electrocardiographic imaging (ECGI) reconstructs the electrical activity of the heart from a dense array of body-surface electrocardiograms and a patient-specific heart-torso geometry. Depending on how it is formulated, ECGI allows the reconstruction of the activation and recovery sequence of the heart, the origin of premature beats or tachycardia, the anchors/hotspots of re-entrant arrhythmias and other electrophysiological quantities of interest. Importantly, these quantities are directly and non-invasively reconstructed in a digitized model of the patient's three-dimensional heart, which has led to clinical interest in ECGI's ability to personalize diagnosis and guide therapy. Despite considerable development over the last decades, validation of ECGI is challenging. Firstly, results depend considerably on implementation choices, which are necessary to deal with ECGI's ill-posed character. Secondly, it is challenging to obtain (invasive) ground truth data of high quality. In this review, we discuss the current status of ECGI validation as well as the major challenges remaining for complete adoption of ECGI in clinical practice. Specifically, showing clinical benefit is essential for the adoption of ECGI. Such benefit may lie in patient outcome improvement, workflow improvement, or cost reduction. Future studies should focus on these aspects to achieve broad adoption of ECGI, but only after the technical challenges have been solved for that specific application/pathology. We propose 'best' practices for technical validation and highlight collaborative efforts recently organized in this field. Continued interaction between engineers, basic scientists, and physicians remains essential to find a hybrid between technical achievements, pathological mechanisms insights, and clinical benefit, to evolve this powerful technique toward a useful role in clinical practice.This study received financial support from the Hein Wellens Fonds, the Cardiovascular Research and Training Institute (CVRTI), the Nora Eccles Treadwell Foundation, the National Institute of General Medical Sciences of the National Institutes of Health (P41GM103545), the National Institutes of Health (NIH HL080093), the French government as part of the Investments of the Future program managed by the National Research Agency (ANR-10-IAHU-04), from the VEGA Grant Agency in Slovakia (2/0071/16), from the Slovak Research and Development Agency (APVV-14-0875), the Fondo Europeo de Desarrollo Regional (FEDER), the Instituto de Salud Carlos III (PI17/01106) and from Conselleria d'Educacio, Investigacio, Cultura i Esport de la Generalitat Valenciana (AICO/2018/267) and NIH grant (HL125998) and National Science Foundation (ACI-1350374).Cluitmans, M.; Brooks, D.; Macleod, RS.; Dossel, O.; Guillem Sánchez, MS.; Van Dam, P.; Svehlikova, J.... 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