369 research outputs found

    Statistical Comparison Of Crystal Orientation Fabrics With Particular Reference To The Fabrics Of Heterogeneously Deformed Quartzite Pebbles Of The Conglomerate From The Tyson Formation, Vermont

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    A highly deformed conglomerate from the Tyson Formation in central Vermont, U.S.A. is the focus of the analysis of the internal fabric of individual, heterogeneously deformed quartzite pebbles. The quartz crystallographic fabric is measured using the optical universal stage and X-ray fabric camera. The grain shape fabric is measured using digitized video camera images.;For the purpose of comparing quartz c-axis orientation patterns, nonparametric tests are investigated. This study is based on a suite of 132 measured quartz c-axis patterns which are representative of all possible types provided by Dr. John Starkey. The insights gained from this study are applied to the more subtle variations in the quartz c-axis patterns displayed by the heterogeneously deformed pebbles.;The c-axis fabrics of the quartzite pebbles show single girdle and crossed-girdle patterns which can be reconciled with plane strain deformation. Further, the crossed-girdle patterns are symmetrically oriented relative to the foliation which therefore indicates coaxial deformation. However, in some crossed-girdle patterns, one girdle is stronger suggesting local non-coaxial deformation. Both strain paths probably developed under conditions of plane strain.;The Mann-Whitney, Kolmogorov-Smirnov and Squared rank test statistics are derived by comparing 32 selected, recognizable types of measured quartz c-axis orientation patterns with the uniform reference pattern. Two groups of test statistics were found, a group of clustered pattern types and a group of dispersed pattern types. The data for all pattern types can be grouped according to their statistics, except cleft girdles and double maxima.;The nonparametric statistical tests are also used to compare two measured orientation patterns in an objective and reproducible manner. The Mann-Whitney and Kolmogorov-Smirnov tests confirmed the similarity of patterns which visual comparison would show as similar. However, the Squared ranks test proved to be too sensitive in comparing the measured orientation patterns with each other.;The comparison of the orientation patterns from the heterogeneously deformed pebbles of the Tyson conglomerate showed that the orientation patterns were similar in almost every case. However, the orientation patterns were found to be different between the different pebbles

    Serotonin 1A Receptor Signaling in the Hypothalamic Paraventricular Nucleus of the Peripubertal Rat

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    Serotonin (5-HT) is a ubiquitous neurotransmitter in the brain that is involved in various physiologic functions including the regulation of hypothalamic hormones and has been implicated in various mood disorders such as depression. Preclinical and clinical data from studies in adults have shown that antidepressant drugs produce time-dependent changes in serotonergic and other systems and can also normalize dysfunction associated with the hypothalamic-pituitary-adrenal (HPA) axis. To date, our understanding of the mechanisms of 5-HT receptor signaling and the actions of drugs on serotonergic function have been derived from extensive preclinical research carried out using cell lines in vitro or in adult animal models in vivo. Fewer studies have investigated serotonergic signaling mechanisms or the effects of antidepressants (i.e., selective serotonin reuptake inhibitors (SSRIs)) in animal models prior to sexual maturation. This is a scientific and clinically relevant issue as (1) SSRIs, the most effective pharmacological option for treating mood disorders in children and adolescents, are being increasingly prescribed and may be associated with suicidal thoughts or behaviors in these age groups and (2) preclinical studies in rodents indicate that SSRI-induced modulation of the serotonergic system prior to sexual maturation produces effects that are distinct and more long-lasting than those produced in adults. To date, few if any studies have investigated mechanisms of 5-HT receptor signal transduction in peripubertal hypothalamic neurons in vivo and their regulation by SSRIs, despite a wealth of existing comparative data on serotonin 1A (5-HT1A) receptor signaling in adult hypothalamic rat paraventricular nucleus (PVN). Given the clinical relevance of potential age-dependent differences in serotonergic signaling and regulation of hypothalamic function, the objective of the studies in this dissertation was to identify and characterize the mechanisms of 5-HT1A receptor signaling in the peripubertal hypothalamic PVN. The data generated by studies in this dissertation project provide the first in vivo evidence that 5-HT1A receptors in the peripubertal PVN can activate multiple responses: (1) oxytocin and adrenocorticotropic hormone (ACTH) plasma hormone responses, (2) activation of extracellular signal-regulated kinase (ERK), and (3) activation of protein kinase B (Akt). The data also demonstrate that these pathways may be differentially responsive to different classes of 5-HT1A receptor agonists. (+)8-OH-DPAT (an aminotetralin), acted as a full agonist on each of the respective pathways, while tandospirone (an azapirone) exhibited partial agonist activity on activation of Akt but exhibited full agonist activity on neuroendocrine responses and activation of ERK. 5-HT1A receptors produce a rapid and prolonged activation of ERK in the peripubertal PVN, unlike the rapid but more transient response in the adult PVN. In addition, the 5-HT1A activation of ERK may be expressed only in certain populations of neuroendocrine cells in the peripubertal PVN. These studies have also revealed some unique aspects that G α proteins in the peripubertal PVN, since: (1) there are age-dependent increases only in Gαo levels, (2) Gαi3 and Gαo are not reduced by intra-PVN injection with pertussis toxin, and (3) Gαz proteins are not reduced by 7 or 14 days of fluoxetine treatment. We also have determined that chronic fluoxetine treatment desensitizes 5-HT1A receptor-mediated phosphorylation of GSK3ÎČ in the absence of changes in its canonical upstream kinase, Akt. These data suggest fluoxetine may induce changes in phosphatase activity or that there may be a different upstream kinase mediating the phosphorylation of GSK3ÎČ in the peripubertal PVN. In conclusion, the present studies determined the mechanisms of 5-HT1A receptor-mediated signaling in peripubertal PVN and identified some aspects of 5-HT1A receptor signaling that differ from those previously identified in adults. These findings may be clinically relevant with respect to facilitating a better understanding of mechanisms mediating the therapeutic and/or side effects of SSRIs prescribed to young patients or to identify novel drug targets to treat mood disorders in children and adolescents

    INSULIN RESISTANCE IS ASSOCIATED WITH ALL-CAUSE MORTALITY AND ACCELERATES THE RISK OF PROGRESSION TO DIABETES IN NON DIABETIC HEART FAILURE PATIENTS

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    Background: Heart failure is an insulin resistant state. Insulin resistance is highly prevalent in non-diabetic patients with heart failure. The impact of insulin resistance on the development of diabetes mellitus and mortality has not been fully defined. The purpose of this study was to investigate whether insulin resistance is associated with all-cause mortality in a group of non-diabetic patients with heart failure. We have also investigated the impact of insulin resistance on the conversion to diabetes mellitus in these patients. Methods: Insulin resistance, defined by fasting Insulin resistance index (FIRI≄2.7) was assessed in 121 consecutive CHF patients (69 ± 10, 22 % females, 81% ischemic, 61% insulin resistant and FIRI of 4.19 ± 3.8 at baseline) and was followed up for their most recent HbA1c/FPG measurements and mortality data using the electronic linkage system in Dundee, UK. The primary outcome for these cohorts of patients was all cause mortality and secondary outcome was the development of diabetes mellitus.). Cox proportional hazard models were used with FIRI as a continuous variable. Results: After a 6.6 years (IQR 4.7-6.9) median follow-up period, 46 (38%) patients died. A cox proportional hazard model adjusted for relevant covariates showed that the degree of insulin resistance, was significantly associated (HR 1.09, CI 95% 1.02- 1.16), p =0.008) with all-cause mortality. Of the 81 patients we followed up for the development of diabetes, 29% of Insulin resistant-heart failure patients developed diabetes, compared to 10% of non-Insulin resistant-CHF patients. Conclusion: In conclusion, higher FIRI relates to higher all-cause mortality in heart failure patients. We also found out that heart failure patients with IR are at high risk of developing diabetes

    Community Hubs in Lancashire and South Cumbria: Emergence, Development and Next Steps Research Project: Final Report

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    Background, Rationale and Community Hub Characterisation This report summarises research into the emergence and development of community hubs within Lancashire and South Cumbria (L&SC). The project has been funded by the University of Central Lancashire (UCLan) and was developed following discussions with the Partnerships Manager at Community Futures – the Community Council of Lancashire. The phrase ‘community hub’ has existed for a number of years and usually relates to a range of community initiatives, including community centres, community spaces, and many other projects that provide services to a community [1, 2]. Most of these initiatives have originated in the Voluntary, Community, Faith and Social Enterprise (VCFSE) sector. However, since the proliferation of community hubs during the COVID-19 pandemic, hubs operated by district-level local authorities have emerged in greater number. These are perceived to have been a successful response to the challenges posed by the pandemic, and to have reduced barriers to communication between organisations and led to an increase in partnership working [3]. In L&SC there are a couple of large programmes being developed by public bodies such as Lancashire County Council and the local NHS foundation trust that build on the theme of community hubs. The range of initiatives that the phrase ‘community hub’ can refer to has created some confusion amongst members of the VCFSE sector who are unsure how these programmes will affect them and what role, if any, they may be expected to fulfil within them. At times there is little agreement (and some tautology) over what constitutes either a ‘community’ or a ‘hub’ – ‘community’ indicating the constituents served by a hub, and ‘hub’ referring to the nature of the community initiative in question. This report begins by outlining the geographical parameters of the study in the context of the L&SC Integrated Care System (ICS) before considering definitional issues, drawing on insights from the literature and our research interviews. It then sets out the study’s aim and objectives, summarises the study design and methods, and acknowledges some limitations. It goes on to introduce the ‘landscape’ of community hubs, before presenting findings from the qualitative data collection – examining the development of community hubs; motivations and drivers; challenges; facilitators; and public-civil society tensions

    Community Hubs in Lancashire and South Cumbria: Emergence, Development and Next Steps Research Project: Final Report – Executive Summary

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    Introduction This report summarises research into the emergence and development of community hubs within Lancashire and South Cumbria (L&SC). The project has been funded by the University of Central Lancashire (UCLan) and was developed following discussions with the Partnerships Manager at Community Futures – the Community Council of Lancashire. It acknowledges a degree of confusion and overlap regarding hubs in the L&SC region, some led by the VCSFE and others by the statutory sector. It addresses differences in perceptions of the role and function of hubs and aims to give an overview of the emerging landscape, challenges, motivations and drivers for hub formation, as well as reflecting on public and VCFSE sector perspectives. Aims and Objectives Aims a) To characterise the emergence and development of community hubs in Lancashire and Cumbria, accounting for their diversity and the key challenges they are attempting to address. b) To inform the development of a joined-up, coherent and sustainable approach to establishing effective community hubs in L&SC. Objectives a) To examine the approaches to developing and resourcing community hubs within L&SC. b) To gain an overview of existing and proposed community hub-related developments within L&SC. c) To increase understanding of how these community hub-related developments are responding to community need, infrastructure and provision. d) To underpin a joined-up approach to working across sectors within L&SC and produce policy recommendations that can lead to better outcomes and less duplication. Methods The study followed a mixed-methods approach and ethical approval was secured from the relevant UCLan Ethics Committee. Three phases of data collection included: Desk-based research and mapping exercise. Semi-structured interviews with decision makers and project managers from public bodies. Small-group and individual interviews with participants from a sample of community hubs

    Drawing on Indigenous Governance and Stewardship to Build Resilient Coastal Fisheries: People and Abalone along Canada\u27s Northwest Coast

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    Small-scale indigenous abalone fisheries on the northwest coast of Canada persisted for at least two millennia prior to modern commercial and recreational fisheries that lasted for four decades before collapsing, causing a coast wide closure that remains today. What traditional governance and stewardship practices fostered resilient fisheries along Canada’s northwest coast and how might they inform collaborative institutions that foster ecologically sustainable and socially just coastal fisheries in future? In collaboration with two coastal First Nations, a policy analysis of northern abalone (GaalGuuhlkyan (Skidegate Haida), ǧaɫǧáč‡Ì“Ă­q̓ (Heiltsuk), Haliotis kamtschatkana) stewardship was conducted to assess where traditional and modern fisheries governance and management aligned or failed to align with seven theoretical principles of socialecological resilience. The analysis revealed that traditional principles of reciprocity and contingent proprietorship of clan-based fishing areas aligned with resilience principles whereas contemporary centralized decision-making and region-wide management policies did not. Moreover, current issues of power asymmetry and lack of trust need to be addressed to build a future indigenous-state governance approach to coastal fisheries. This research demonstrates how indigenous resource governance and stewardship practices generated over millennia of social learning and experimentation offer insights that could be broadly applied to foster resilient coastal fisheries today

    Citizen science to improve patient and public involvement in GUideline Implementation in oral health and DEntistry (the GUIDE platform)

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    Background: Citizen science is a way to democratise science by involving groups of citizens in the research process. Clinical guidelines are used to improve practice, but their implementation can be limited. Involving patients and the public can enhance guideline implementation, but there is uncertainty about the best approaches to achieve this. Citizen science is a potential way to involve patients and the public in improving clinical guideline implementation. We aimed to explore the application of citizen science methods to involve patients and the public in the dissemination and implementation of clinical guidelines in oral health and dentistry. Methods: We developed GUIDE (GUideline Implementation in oral health and DEntistry), a citizen science online platform, using a participatory approach with researchers, oral health professionals, guideline developers and citizens. Recruitment was conducted exclusively online. The platform focused on prespecified challenges related to oral health assessment guidelines, and asked citizens to generate ideas, as well as vote and comment on other citizens' ideas to improve those challenges. Citizens also shared their views via surveys and two online synchronous group meetings. Data were collected on participant's demographics, platform engagement and experience of taking part. The most promising idea category was identified by an advisory group based on engagement, feasibility and relevance. We presented quantitative data using descriptive statistics and analysed qualitative data using inductive and deductive thematic analysis. Results: The platform was open for 6 months and we recruited 189 citizens, from which over 90 citizens actively engaged with the platform. Most citizens were over 34 years (64%), female (58%) and had a university degree (50%). They generated 128 ideas, 146 comments and 248 votes. The challenge that led to most engagement was related to prevention and oral health self-care. To take this challenge forward, citizens generated a further 36 ideas to improve a pre-existing National Health Service oral care prevention leaflet. Citizens discussed motivations to take part in the platform (understanding, values, self-care), reasons to stay engaged (communication and feedback, outputs and impact, and relevance of topics discussed) and suggestions to improve future platforms. Conclusion: Citizen science is an effective approach to generate and prioritise ideas from a group of citizens to improve oral health and dental services. Prevention and oral health self-care were of particular interest to citizens. More research is needed to ensure recruitment of a diverse group of citizens and to improve retention in citizen science projects. Patient or Public Contribution: This project was inherently conducted with the input of public partners (citizen scientists) in all key aspects of its conduct and interpretation. In addition, two public partners were part of the research team and contributed to the design of the project, as well as key decisions related to its conduct, analysis, interpretation and dissemination and are co-authors of this manuscript.</p

    Thyroid Function and Perchlorate in Drinking Water: An Evaluation among California Newborns, 1998

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    Perchlorate (ClO(4)(−)) has been detected in groundwater sources in numerous communities in California and other parts of the United States, raising concerns about potential impacts on health. For California communities where ClO(4)(−) was tested in 1997 and 1998, we evaluated the prevalence of primary congenital hypothyroidism (PCH) and high thyroid-stimulating hormone (TSH) levels among the 342,257 California newborns screened in 1998. We compared thyroid function results among newborns from 24 communities with average ClO(4)(−) concentrations in drinking water > 5 ÎŒg/L (n = 50,326) to newborns from 287 communities with average concentrations ≀5 ÎŒg/L (n = 291,931). ClO(4)(−) concentrations obtained from the California Drinking Water Program provided source-specific data for estimating weighted average concentrations in community water. Fifteen cases of PCH from communities with average concentration > 5 ÎŒg/L were observed, with 20.4 expected [adjusted prevalence odds ratio (POR) = 0.71; 95% confidence interval (CI), 0.40–1.19]. Although only 36% of all California newborns were screened before 24 hr of age in 1998, nearly 80% of newborns with high TSH were screened before 24 hr of age. Because of the physiologic postnatal surge of TSH, the results for newborns screened before 24 hr were uninformative for assessing an environmental impact. For newborns screened ≄24 hr, the adjusted POR for high TSH was 0.73 (95% CI, 0.40–1.23). All adjusted odds ratios (ORs) were controlled for sex, ethnicity, birth weight, and multiple birth status. Using an assessment of ClO(4)(−) in drinking water based on available data, we did not observe an association between estimated average ClO(4)(−) concentrations > 5 ÎŒg/L in drinking water supplies and the prevalence of clinically diagnosed PCH or high TSH concentrations

    Citizen science to improve patient and public involvement in GUideline Implementation in oral health and DEntistry (the GUIDE platform)

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    BackgroundCitizen science is a way to democratise science by involving groups of citizens in the research process. Clinical guidelines are used to improve practice, but their implementation can be limited. Involving patients and the public can enhance guideline implementation, but there is uncertainty about the best approaches to achieve this. Citizen science is a potential way to involve patients and the public in improving clinical guideline implementation. We aimed to explore the application of citizen science methods to involve patients and the public in the dissemination and implementation of clinical guidelines in oral health and dentistry.MethodsWe developed GUIDE (GUideline Implementation in oral health and DEntistry), a citizen science online platform, using a participatory approach with researchers, oral health professionals, guideline developers and citizens. Recruitment was conducted exclusively online. The platform focused on prespecified challenges related to oral health assessment guidelines, and asked citizens to generate ideas, as well as vote and comment on other citizens' ideas to improve those challenges. Citizens also shared their views via surveys and two online synchronous group meetings. Data were collected on participant's demographics, platform engagement and experience of taking part. The most promising idea category was identified by an advisory group based on engagement, feasibility and relevance. We presented quantitative data using descriptive statistics and analysed qualitative data using inductive and deductive thematic analysis.ResultsThe platform was open for 6 months and we recruited 189 citizens, from which over 90 citizens actively engaged with the platform. Most citizens were over 34 years (64%), female (58%) and had a university degree (50%). They generated 128 ideas, 146 comments and 248 votes. The challenge that led to most engagement was related to prevention and oral health self-care. To take this challenge forward, citizens generated a further 36 ideas to improve a pre-existing National Health Service oral care prevention leaflet. Citizens discussed motivations to take part in the platform (understanding, values, self-care), reasons to stay engaged (communication and feedback, outputs and impact, and relevance of topics discussed) and suggestions to improve future platforms.ConclusionCitizen science is an effective approach to generate and prioritise ideas from a group of citizens to improve oral health and dental services. Prevention and oral health self-care were of particular interest to citizens. More research is needed to ensure recruitment of a diverse group of citizens and to improve retention in citizen science projects
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