761 research outputs found

    The Development and Implementation of the Off-Premise Outlet Density Expansion Initiative within Ontario\u27s New Beer Framework: A Case Study

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    Background: In April 2015, the Ontario government announced the expansion of beer sales in up to 450 grocery stores, thereby substantially increasing access to alcohol. This policy was introduced despite a robust body of research demonstrating a positive relationship between increased outlet density, alcohol consumption, and consequent harm. Methods: This qualitative case study explored the role of health information, and the contexts and factors which shaped its use, in the development and implementation of Ontario’s policy to expand alcohol outlet density. Kingdon’s Streams Model (2011) guided a directed content analysis of policy-related documents (n=69) and transcripts from semi-structured interviews with a range of policy actors, including government policymakers, alcohol researchers, knowledge translation actors, and media personnel (n=11). Results: The grocery outlet expansion initiative was framed as an economic and consumer convenience initiative within policy-related documents. Moreover, many interview participants perceived that the decision to implement the expansion preceded stakeholder consultations. Thus, despite efforts to highlight concern regarding increases to outlet density, knowledge translation strategies by public health actors remained reactive and unpersuasive. Accordingly, the policy appears largely incongruent with pre-existing public health frameworks, including a Health in All Policies approach more broadly. Conclusion: Health information pertaining to outlet density appears to have had a minimal role in informing the development and implementation of Ontario’s expansion policy. The Ontario government is encouraged prioritize health considerations in future policy development to prevent potential unintended consequences to population health

    Implementing Health Impact Assessment as a Required Component of Government Policymaking: A Multi-Level Exploration of the Determinants of Healthy Public Policy

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    It is widely understood that the public policies of ‘non-health’ government sectors have greater impacts on population health than those of the traditional healthcare realm. Health Impact Assessment (HIA) is a decision support tool that identifies and promotes the health benefits of policies while also mitigating their unintended negative consequences. Despite numerous calls to do so, the Ontario government has yet to implement HIA as a required component of policy development. This dissertation therefore sought to identify the contexts and factors that may both enable and impede HIA use at the sub-national (i.e., provincial, territorial, or state) government level. The three integrated articles of this dissertation provide insights into specific aspects of the policy process as they relate to HIA. Chapter one details a case study of purposive information-seeking among public servants within Ontario’s Ministry of Education (MOE). Situated within Ontario’s Ministry of Health (MOH), chapter two presents a case study of policy collaboration between health and ‘non-health’ ministries. Finally, chapter three details a framework analysis of the political factors supporting health impact tool use in two sub-national jurisdictions – namely, Québec and South Australia. MOE respondents (N=9) identified four components of policymaking ‘due diligence’, including evidence retrieval, consultation and collaboration, referencing, and risk analysis. As prospective HIA users, they also confirmed that information is not routinely sought to mitigate the potential negative health impacts of education-based policies. MOH respondents (N=8) identified the bureaucratic hierarchy as the brokering mechanism for inter-ministerial policy development. As prospective HIA stewards, they also confirmed that the ministry does not proactively flag the potential negative health impacts of non-health sector policies. Finally, ‘lessons learned’ from case articles specific to Québec (n=12) and South Australia (n=17) identified the political factors supporting tool use at different stages of the policy cycle, including agenda setting (‘policy elites’ and ‘political culture’), implementation (‘jurisdiction’), and sustained implementation (‘institutional power’). This work provides important insights into ‘real life’ policymaking. By highlighting existing facilitators of and barriers to HIA use, the findings offer a useful starting point from which proponents may tailor context-specific strategies to sustainably implement HIA at the sub-national government level

    Review of Ground Systems Development and Operations (GSDO) Tools for Verifying Command and Control Software

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    The Exploration Systems Development (ESD) Standing Review Board (SRB) requested the NASA Engineering and Safety Center (NESC) conduct an independent review of the plan developed by Ground Systems Development and Operations (GSDO) for identifying models and emulators to create a tool(s) to verify their command and control software. The NESC was requested to identify any issues or weaknesses in the GSDO plan. This document contains the outcome of the NESC review

    Ovulation Leads Women to Perceive Sexy Cads as Good Dads

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    Why do some women pursue relationships with men who are attractive, dominant, and charming but who do not want to be in relationships—the prototypical sexy cad? Previous research shows that women have an increased desire for such men when they are ovulating, but it is unclear why ovulating women would think it is wise to pursue men who may be unfaithful and could desert them. Using both college-age and community-based samples, in 3 studies we show that ovulating women perceive charismatic and physically attractive men, but not reliable and nice men, as more committed partners and more devoted future fathers. Ovulating women perceive that sexy cads would be good fathers to their own children but not to the children of other women. This ovulatory-induced perceptual shift is driven by women who experienced early onset of puberty. Taken together, the current research identifies a novel proximate reason why ovulating women pursue relationships with sexy cads, complementing existing research that identifies the ultimate, evolutionary reasons for this behavior

    Homicide in the context of psychosis: analysis of prior service utilisation and age at onset of illness and violence

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    Background Public stigma and fear are heightened in cases of extreme violence perpetrated by persons with serious mental illness (SMI). Prevention efforts require understanding of illness patterns and treatment needs prior to these events unfolding. Aims To examine mental health service utilisation by persons who committed homicide and entered into forensic care, to investigate the adequacy of mental healthcare preceding these offences. Method Forensic patients across two mental health hospitals in Ontario with an admitting offence of homicide between 2011 and 2021 were identified (n = 112). Sociodemographic, clinical and offence-related variables were coded from the health record and reports prepared for the forensic tribunal. Results Most patients (75.7%) had mental health contacts preceding the homicide, with 28.4% having a psychiatric in-patient admission in the year prior. For those with service contacts in the year preceding, 50.9% had had only sporadic contact and 70.7% were non-adherent with prescribed medications. Victims were commonly known to the individual (35.7%) and were often family members in care-providing roles (55.4%). Examination of age at onset of illness and offending patterns suggested that most persons admitted to forensic care for homicide act in the context of illness and exhibit a low frequency of pre-homicide offending. Conclusions Many individuals admitted to forensic care for homicide have had inadequate mental healthcare leading up to this point. Effective responses to reduce and manage risk should encompass services that proactively address illness-related (e.g. earlier access and better maintenance in care) and criminogenic (e.g. substance use treatment, employment and psychosocial supports) domains

    The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

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    Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines

    Separation of intra-S checkpoint protein contributions to DNA replication fork protection and genomic stability in normal human fibroblasts

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    The ATR-dependent intra-S checkpoint protects DNA replication forks undergoing replication stress. The checkpoint is enforced by ATR-dependent phosphorylation of CHK1, which is mediated by the TIMELESS-TIPIN complex and CLASPIN. Although loss of checkpoint proteins is associated with spontaneous chromosomal instability, few studies have examined the contribution of these proteins to unchallenged DNA metabolism in human cells that have not undergone carcinogenesis or crisis. Furthermore, the TIMELESS-TIPIN complex and CLASPIN may promote replication fork protection independently of CHK1 activation. Normal human fibroblasts (NHF) were depleted of ATR, CHK1, TIMELESS, TIPIN or CLASPIN and chromosomal aberrations, DNA synthesis, activation of the DNA damage response (DDR) and clonogenic survival were evaluated. This work demonstrates in NHF lines from two individuals that ATR and CHK1 promote chromosomal stability by different mechanisms that depletion of CHK1 produces phenotypes that resemble more closely the depletion of TIPIN or CLASPIN than the depletion of ATR, and that TIMELESS has a distinct contribution to suppression of chromosomal instability that is independent of its heterodimeric partner, TIPIN. Therefore, ATR, CHK1, TIMELESS-TIPIN and CLASPIN have functions for preservation of intrinsic chromosomal stability that are separate from their cooperation for activation of the intra-S checkpoint response to experimentally induced replication stress. These data reveal a complex and coordinated program of genome maintenance enforced by proteins known for their intra-S checkpoint function

    Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

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    Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions

    Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects.</p> <p>Methods/Design</p> <p>The EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-β1b will be randomized to additionally receive either high-dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters.</p> <p>Discussion</p> <p>In light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01440062">NCT01440062</a></p

    SWI/SNF complexes are required for full activation of the DNA-damage response

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    SWI/SNF complexes utilize BRG1 (also known as SMARCA4) or BRM (also known as SMARCA2) as alternative catalytic subunits with ATPase activity to remodel chromatin. These chromatin-remodeling complexes are required for mammalian development and are mutated in ~20% of all human primary tumors. Yet our knowledge of their tumor-suppressor mechanism is limited. To investigate the role of SWI/SNF complexes in the DNA-damage response (DDR), we used shRNAs to deplete BRG1 and BRM and then exposed these cells to a panel of 6 genotoxic agents. Compared to controls, the shRNA knockdown cells were hypersensitive to certain genotoxic agents that cause double-strand breaks (DSBs) associated with stalled/collapsed replication forks but not to ionizing radiation-induced DSBs that arise independently of DNA replication. These findings were supported by our analysis of DDR kinases, which demonstrated a more prominent role for SWI/SNF in the activation of the ATR-Chk1 pathway than the ATM-Chk2 pathway. Surprisingly, γH2AX induction was attenuated in shRNA knockdown cells exposed to a topoisomerase II inhibitor (etoposide) but not to other genotoxic agents including IR. However, this finding is compatible with recent studies linking SWI/SNF with TOP2A and TOP2BP1. Depletion of BRG1 and BRM did not result in genomic instability in a tumor-derived cell line but did result in nucleoplasmic bridges in normal human fibroblasts. Taken together, these results suggest that SWI/SNF tumor-suppressor activity involves a role in the DDR to attenuate replicative stress and genomic instability. These results may also help to inform the selection of chemotherapeutics for tumors deficient for SWI/SNF function
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