"It was the whole picture" a mixed methods study of successful components in an integrated wellness service in North East England

Background A growing number of Local Authorities (LAs) have introduced integrated wellness services as part of efforts to deliver cost effective, preventive services that address the social determinants of health. This study examined which elements of an integrated wellness service in the north east of England were effective in improving health and wellbeing (HWB). Methods The study used a mixed-methods approach. In-depth semi-structured interviews (IVs) were conducted with integrated wellness service users (n = 25) and focus groups (FGs) with group based service users (n = 14) and non-service users (n = 23) to gather the views of stakeholders. Findings are presented here alongside analysis of routine monitoring data. The different data were compared to examine what each data source revealed about the effectiveness of the service. Results Findings suggest that integrated wellness services work by addressing the social determinants of health and respond to multiple complex health and social concerns rather than single issues. The paper identifies examples of ‘active ingredients’ at the heart of the programme, such as sustained relationships, peer support and confidence building, as well as the activities through which changes take place, such as sports and leisure opportunities which in turn encourage social interaction. Wider wellbeing outcomes, including reduced social isolation and increased self-efficacy are also reported. Practical and motivational support helped build community capacity by encouraging community groups to access funding, helped navigate bureaucratic systems, and promoted understanding of marginalised communities. Fully integrated wellness services could support progression opportunities through volunteering and mentoring. Conclusions An integrated wellness service that offers a holistic approach was valued by service users and allowed them to address complex issues simultaneously. Few of the reported health gains were captured in routine data. Quantitative and qualitative data each offered a partial view of how effectively services were working

Embedded Research::a promising way to create evidence-informed impact in public health?

Background Embedded research (ER) is recognized as one way to strengthen the integration of evidence into public health (PH) practice. In this paper, we outline a promising example of the co-production of research evidence between Fuse, the UKCRC Centre for Translational Research in Public Health and a local authority (LA) in north east England. Methods We critically examine attempts to share and use research findings to influence decision-making in a LA setting, drawing on insights from PH practitioners, managers, commissioners and academic partners involved in this organizational case study. We highlight what can be achieved as a co-located embedded researcher. Results The benefits and risks of ER are explored, alongside our reflections on the added value of this approach and the institutional prerequisites necessary for it to work. We argue that while this is not a new methodological approach, its application in PH as a way to facilitate evidence use is novel, and raises pragmatic and theoretical questions about the nature of impact and the extent to which it can be engineered. Conclusion With increased situated understanding of organizational culture and norms and greater awareness of the socio-political realities of PH, ER enables new co-produced solutions to become possible

Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

Background: Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings: We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genomewide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79 % and 56–66 % of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions: We identified novel candidate genes associated with variation in resistance to oxidative stress that hav

Deletion of the Mitochondrial Superoxide Dismutase sod-2 Extends Lifespan in Caenorhabditis elegans

The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS) generated during normal metabolism. Superoxide dismutases (SODs) counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice results in decreased lifespan. In this experiment, we examine the effect of eliminating each of the five individual sod genes present in Caenorhabditis elegans. In contrast to what is observed in other model organisms, none of the sod deletion mutants shows decreased lifespan compared to wild-type worms, despite a clear increase in sensitivity to paraquat- and juglone-induced oxidative stress. In fact, even mutants lacking combinations of two or three sod genes survive at least as long as wild-type worms. Examination of gene expression in these mutants reveals mild compensatory up-regulation of other sod genes. Interestingly, we find that sod-2 mutants are long-lived despite a significant increase in oxidatively damaged proteins. Testing the effect of sod-2 deletion on known pathways of lifespan extension reveals a clear interaction with genes that affect mitochondrial function: sod-2 deletion markedly increases lifespan in clk-1 worms while clearly decreasing the lifespan of isp-1 worms. Combined with the mitochondrial localization of SOD-2 and the fact that sod-2 mutant worms exhibit phenotypes that are characteristic of long-lived mitochondrial mutants—including slow development, low brood size, and slow defecation—this suggests that deletion of sod-2 extends lifespan through a similar mechanism. This conclusion is supported by our demonstration of decreased oxygen consumption in sod-2 mutant worms. Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm lifespan by altering mitochondrial function

Quantitative and Molecular Genetic Analyses of Mutations Increasing Drosophila Life Span

Understanding the genetic and environmental factors that affect variation in life span and senescence is of major interest for human health and evolutionary biology. Multiple mechanisms affect longevity, many of which are conserved across species, but the genetic networks underlying each mechanism and cross-talk between networks are unknown. We report the results of a screen for mutations affecting Drosophila life span. One third of the 1,332 homozygous P–element insertion lines assessed had quantitative effects on life span; mutations reducing life span were twice as common as mutations increasing life span. We confirmed 58 mutations with increased longevity, only one of which is in a gene previously associated with life span. The effects of the mutations increasing life span were highly sex-specific, with a trend towards opposite effects in males and females. Mutations in the same gene were associated with both increased and decreased life span, depending on the location and orientation of the P–element insertion, and genetic background. We observed substantial—and sex-specific—epistasis among a sample of ten mutations with increased life span. All mutations increasing life span had at least one deleterious pleiotropic effect on stress resistance or general health, with different patterns of pleiotropy for males and females. Whole-genome transcript profiles of seven of the mutant lines and the wild type revealed 4,488 differentially expressed transcripts, 553 of which were common to four or more of the mutant lines, which include genes previously associated with life span and novel genes implicated by this study. Therefore longevity has a large mutational target size; genes affecting life span have variable allelic effects; alleles affecting life span exhibit antagonistic pleiotropy and form epistatic networks; and sex-specific mutational effects are ubiquitous. Comparison of transcript profiles of long-lived mutations and the control line reveals a transcriptional signature of increased life span

Ancient goat genomes reveal mosaic domestication in the Fertile Crescent

Current genetic data are equivocal as to whether goat domestication occurred multiple times or was a singular process. We generated genomic data from 83 ancient goats (51 with genome-wide coverage) from Paleolithic to Medieval contexts throughout the Near East. Our findings demonstrate that multiple divergent ancient wild goat sources were domesticated in a dispersed process that resulted in genetically and geographically distinct Neolithic goat populations, echoing contemporaneous human divergence across the region. These early goat populations contributed differently to modern goats in Asia, Africa, and Europe. We also detect early selection for pigmentation, stature, reproduction, milking, and response to dietary change, providing 8000-year-old evidence for human agency in molding genome variation within a partner species

Role of Nrf2 Dysfunction in Uremia-Associated Intestinal Inflammation and Epithelial Barrier Disruption

Aims: To study the expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls, and demonstrate the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent Nrf2 activator

Adsorption Rate of Iron onto Primary Incisor Teeth Following the Application of Three Iron Drops

Abstract: Background & Aims: Iron deficiency anemia is the most common kind of anemia in childhood. Iron supplements that are usually prescribed for the treatment stain teeth. The purpose of this study was an in vitro comparison of the adsorption rate of iron onto incisor primary teeth after exposure to three different Iron drops (Darupakhash, Fer–In– Sol, Shahredaru). Methods: This study was performed on sixty intact primary incisor teeth in two stages with one week interval. In each stage thirty teeth were examined. The teeth in each stage were divided into three groups and each group was exposed to one kind of Iron drop. The rate of Iron adsorption was measured by Atomic Absorption system. ANOVA (Kruskal – wallis) test was used for statistical analysis. Results: There was a significant difference among three types of Iron drops in adsorption of Iron (P<0.001). Fer–In–Sol had the least and darupakhash had the highest adsorption rate. Conclusion: Although all three Iron drops cause stain on primary incisor teeth, there is a significant difference among them. Keywords: Iron Salts, Adsorption, Tooth discoloratio

Online condition monitoring of floating wind turbines drivetrain by means of digital twin

This paper presents a digital twin (DT) condition monitoring approach for drivetrains on floating offshore wind turbines. Digital twin in this context consists of torsional dynamic model, online measurements and fatigue damage estimation which is used for remaining useful life (RUL) estimation. At first, methods for system parameter estimation are presented. The digital twin model provides sufficient inputs for the load observers designed in specific points of the drivetrain to estimate the online load and subsequently stress in the different components. The estimated real-time stress values feed the degradation model of the components. The stochastic degradation model proposed for estimation of real-time fatigue damage in the components is based on a proven model-based approach which is tested under different drivetrain operations, namely normal, faulty and overload conditions. The uncertainties in model, measurements and material properties are addressed, and confidence interval for the estimations is provided by a detailed analysis on the signal behavior and using Monte Carlo simulations. A test case, using 10 MW drivetrain, has been demonstrated

Evaluation of PMSG-based drivetrain technologies for 10 MW floating offshore wind turbines: pros and cons in a life-cycle perspective

This paper presents an in depth evaluation and comparison of three different drivetrain choices based on permanent‐magnet synchronous generator (PMSG) technology for 10‐MW offshore wind turbines. The life cycle approach is suggested to evaluate the performance of the different under consideration drivetrain topologies. Furthermore, the design of the drivetrain is studied through optimized designs for the generator and gearbox. The proposed drivetrain analytical optimization approach supported by numerical simulations shows that application of gearbox in 10‐MW offshore wind turbines can help to reduce weight, raw material cost, and size and simultaneously improve the efficiency. The possibility of resonance with the first torsional natural frequency of drivetrain for the different designed drivetrain systems, the influence of gear ratio, and the feasibility of the application for a spar floating platform are also discussed. This study gives evidence on how gearbox can mitigate the torque oscillation consequences on the other components and how the latter can influence the reliability of drivetrain