256 research outputs found
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Regulation of chemokines and IL-6 production in human mesangial cells: Potential role in glomerulonephritis
Available from British Library Document Supply Centre-DSC:DXN008417 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
Actual neighborhood-level crime predicts body mass index z-score changes in a multi-racial/ethnic sample of children
Longitudinal studies are warranted to clarify the influence crime has on health outcomes in children especially
children representing multiple racial/ethnic backgrounds. To address this need, the current study examined
whether neighborhood-level crime predicted changes in body mass index z (BMIz) scores in 373 White (W), 627
African American (AA), 1020 Hispanic (H), and 88 Asian (A), five to ten year-old boys and girls living in urban
neighborhoods. Heights and weights were assessed at baseline (2012) and three-years later and used to calculate
BMIz scores. Characteristics of zip codes where students lived during the three-year period were obtained at
baseline from various sources. The Crime Risk Index (CRI) for each zip code was calculated using actual crime
statistics. Multiple linear regression analyses were conducted to examine associations between baseline CRI and
follow-up BMIz scores while controlling for other variables including BMIz at baseline. The CRI and BMIz scores
differed significantly by race/ethnicity with the highest values for both noted in H. Regression analyses indicated
that the CRI accounted for a significant percentage of the variance in follow-up BMIz scores in the overall
sample. When race/ethnicity was considered, the CRI predicted follow-up BMIz scores only in W children. The
CRI was not significantly associated with BMIz scores in the other races/ethnicities. The impact actual, neighborhood-level crime has on BMI in children is complex. Based on the existing evidence, considering actual crime
as a primary target in obesity prevention would be premature especially in racial/ethnicity minority children
living in urban areas
Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia
Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the
Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC
This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing
Consensus of the definitions of the OMERACT glucocorticoid impact core domain set for people with rheumatic and musculoskeletal diseases
Background: The Outcome Measures in Rheumatology (OMERACT) Glucocorticoid (GC) Impact Working Grouphas been working to develop a core domain set to measure the impact of GCs on patients living with rheumaticand musculoskeletal diseases. The mandatory domains previously identified for inclusion in all clinical trialsmeasuring the GC effects include infection, bone fragility, mood disturbance, hypertension, diabetes, weight,fatigue, and mortality. Before progressing to instrument selection, the Working Group sought to establish precisedefinitions of all mandatory domains within the core domain set.Methods: OMERACT methodology was applied with the use of evidence and consensus-based decision making ofall stakeholder groups (patient research partners, health care professionals, clinician researchers, industrymembers and methodologists) to develop detailed definitions for the broad domain, target domain and domaincomponents, taking into consideration sources of variability that could affect measurement of the domain. Theworking group synthesized prior qualitative studies, quantitative work, and results from Delphi rounds, todevelop a rich definition of ‘what’ is to be measured.Results: Between 2021 and 2023, the OMERACT Working Group on GC Impact conducted virtual meetings toestablish domain definitions. First, we mapped each domain onto an OMERACT Core Area. All domains wereprimarily represented within the Pathophysiological Manifestations Core Area, except from Fatigue which wasprimarily Life Impact and Weight which spanned both Core Areas. Sources of variability included cultural factors, age, gender, education level, socioeconomic status, personal experiences, emotional state, and languagebarriers. The domain definitions will form the foundation for instrument selection and the initial step of domain /concept match and content validity in the OMERACT pillar of ‘truth’ before moving on to feasibility anddiscrimination.Conclusion: The OMERACT GC Impact Working Group has developed and agreed upon detailed domain definitions for core domains. Future steps of the working group are to select instruments and develop the core outcom
Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.
Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies
Embedding reflexivity within experiential qualitative psychology
In this article, it is argued that reflexivity is integral to experiential qualitative research in psychology. Reflexivity has been defined in many ways. Woolgar’s continuum of reflexivity though provides a useful gauge by which to judge whether a researcher is involved in simple reflection or reflexivity. The article demonstrates the benefits of adopting a reflexive attitude by presenting “challenge-to-competency.” The author’s encounter with Sarah will help illustrate the role of reflexivity both in data generation and in interpretative analysis. To close, it is proposed that reflexivity as hermeneutic reflection, with its grounding in hermeneutics and phenomenology, is a useful construct for guiding our engagement in reflexivity in experiential qualitative research
The success of the Montreal Protocol in mitigating interactive effects of stratospheric ozone depletion and climate change on the environment
The Montreal Protocol and its Amendments have been highly effective in protecting the stratospheric ozone layer, preventing global increases in solar ultraviolet-B radiation (UV-B; 280-315 nm) at Earth's surface, and reducing global warming. While ongoing and projected changes in UV-B radiation and climate still pose a threat to human health, food security, air and water quality, terrestrial and aquatic ecosystems, and construction materials and fabrics, the Montreal Protocol continues to play a critical role in protecting Earth's inhabitants and ecosystems by addressing many of the United Nations Sustainable Development Goals.Non peer reviewe
Be SMART:examining the experience of implementing the NHS Health Check in UK primary care
Background: The NHS Health Check was designed by UK Department of Health to address increased prevalence of cardiovascular disease by identifying risk levels and facilitating behaviour change. It constituted biomedical testing, personalised advice and lifestyle support. The objective of the study was to explore Health Care Professionals' (HCPs) and patients' experiences of delivering and receiving the NHS Health Check in an inner-city region of England. Methods: Patients and HCPs in primary care were interviewed using semi-structured schedules. Data were analysed using Thematic Analysis. Results: Four themes were identified. Firstly, Health Check as a test of 'roadworthiness' for people. The roadworthiness metaphor resonated with some patients but it signified a passive stance toward illness. Some patients described the check as useful in the theme, Health check as revelatory. HCPs found visual aids demonstrating levels of salt/fat/sugar in everyday foods and a 'traffic light' tape measure helpful in communicating such 'revelations' with patients. Being SMART and following the protocolrevealed that few HCPs used SMART goals and few patients spoke of them. HCPs require training to understand their rationale compared with traditional advice-giving. The need for further follow-up revealed disparity in follow-ups and patients were not systematically monitored over time. Conclusions: HCPs' training needs to include the use and evidence of the effectiveness of SMART goals in changing health behaviours. The significance of fidelity to protocol needs to be communicated to HCPs and commissioners to ensure consistency. Monitoring and measurement of follow-up, e.g., tracking of referrals, need to be resourced to provide evidence of the success of the NHS Health Check in terms of healthier lifestyles and reduced CVD risk
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