23 research outputs found

    Physical activity is a potential measure of physical resilience in older adults receiving hemodialysis

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    BackgroundPhysical resilience, or the ability to recover after a physical stressor, declines with aging. Efforts to preserve physical resilience in the older dialysis population are critically needed; however, validated, patient-centered measures that are sensitive to change are also needed. Our objective was to assess accelerometer-derived step count variability, or a measure of intra-individual variation in physical activity, as a potential measure of physical resilience among older adults receiving hemodialysis.MethodsCommunity-dwelling ambulatory older adults receiving in-center hemodialysis were prospectively enrolled. Participants wore wrist accelerometers during daytime hours on both dialysis and non-dialysis days up to 14 days, and the feasibility of accelerometer use was assessed from wear time. We used accelerometer data to compute step counts in 4-hour blocks and step count variability. Physical function was assessed with the Short Physical Performance Battery (SPPB which includes gait speed test), grip strength, activities of daily living (ADLs) instruments, and life space mobility. We assessed interval fatigue (subjective rating from 0 to 10) on dialysis and non-dialysis days and self-reported recovery time. We assessed the correlations of step count variability with measures of physical function and step count and interval fatigue.ResultsOf 37 enrolled participants, 29 had sufficient accelerometer data for analyses. Among the 29 participants, mean (SD) age was 70.6(4.8) years, and 55% (n=16) were male and 72% (n=21) were Black race. Participants were largely sedentary with median (Q1-Q3) self-reported total kilocalories per week of 200 (36鈥552). Step count variability was positively correlated with measures of physical function: SPPB (r=0.50, p<0.05), gait speed (r=0.59, p<0.05), handgrip strength (r=0.71, p<0.05), Instrumental ADLs (r=0.44, p<0.05) and life space mobility (r=0.54, p<0.05).There was a weak inverse correlation between post-dialysis step counts (4-hour blocks after a dialysis session) and post-dialysis interval fatigue [r=-0.19 (n=102, p=0.06).ConclusionsPhysical activity assessment via accelerometer is feasible for older adults receiving hemodialysis. Step count variability correlated with physical function, so it may be a novel measure of physical resilience. Further studies are needed to validate this measure

    Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

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    Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7路8 million single nucleotide polymorphisms in 37鈥688 cases, 18鈥618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1路4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16鈥36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0路0035 for intracranial volume, p=0路024 for putamen volume), smoking status (p=0路024), and educational attainment (p=0路038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8路00鈥埫椻10鈭7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

    Using high-resolution contact networks to evaluate SARS-CoV-2 transmission and control in large-scale multi-day events

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    The emergence of highly transmissible SARS-CoV-2 variants has created a need to reassess the risk posed by increasing social contacts as countries resume pre-pandemic activities, particularly in the context of resuming large-scale events over multiple days. To examine how social contacts formed in different activity settings influences interventions required to control Delta variant outbreaks, we collected high-resolution data on contacts among passengers and crew on cruise ships and combined the data with network transmission models. We found passengers had a median of 20 (IQR 10鈥36) unique close contacts per day, and over 60% of their contact episodes were made in dining or sports areas where mask wearing is typically limited. In simulated outbreaks, we found that vaccination coverage and rapid antigen tests had a larger effect than mask mandates alone, indicating the importance of combined interventions against Delta to reduce event risk in the vaccine era

    Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK 鈥楢lert Level 4鈥 phase of the B-MaP-C study

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    Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated 鈥榮tandard鈥 or 鈥楥OVID-altered鈥, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had 鈥楥OVID-altered鈥 management. 鈥楤ridging鈥 endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2鈥9%) using 鈥楴HS Predict鈥. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of 鈥楥OVID-altered鈥 management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

    Intersectionality and employment barriers: analyzing age and gender bias in job advertisements

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    Different forms of discrimination occur within phases of the employment process (attraction, selection, retention), with an estimated 20-40% of employers influenced by bias in their hiring decisions. Sexism and ageism are among the most prevalent forms; however, detecting hiring discrimination is complex and often unreported. The current study focused on the attraction phase to examine how age and gender intersect to create employment barriers and opportunities. A sample of 800 job ads were collected from white-collar, blue-collar, female-and-male-dominated occupations across the U.S. Using a mixed methods approach, data were analyzed through an exploratory, content analysis to identify previous and nuanced gendered and age biased language to develop a repository for LIWC to conduct a series of 2x2 factorial ANOVAs. A significant interaction was found between job industry and gender dominance in the gendered age language bias to indicate a young man candidate. Limitations, future directions, and implications are discussed