Perspectives on Urban Health

Book: iii, 61 pp.,digital file.The Canadian Healthy Communities Project {CHCP) was launched in 1988 as a three-year project to promote municipal involvement in creating healthy communities. In 1991, CHCP will complete three years of its operation, and funding has been extended for a further three-year period. In a way, the papers included in this volume present the challenge, as well as the potential, for improving urban health in contemporary times.Canada Mortgage and Housing Corporatio

Canonical explorations of 'Tel' environments for computer programming

This paper applies a novel technique of canonical gradient analysis, pioneered in ecological sciences, with the aim of exploring student performance and behaviours (such as communication and collaboration) while undertaking formative and summative tasks in technology enhanced learning (TEL) environments for computer programming. The research emphasis is, therefore, on revealing complex patterns, trends, tacit communications and technology interactions associated with a particular type of learning environment, rather than the testing of discrete hypotheses. The study is based on observations of first year programming modules in BSc Computing and closely related joint-honours with software engineering, web and game development courses. This research extends earlier work, and evaluates the suitability of canonical approaches for exploring complex dimensional gradients represented by multivariate and technology-enhanced learning environments. The advancements represented here are: (1) an extended context, beyond the use of the ‘Ceebot’ learning platform, to include learning-achievement following advanced instruction using an industrystandard integrated development environment, or IDE, for engineering software; and (2) longitudinal comparison of consistency of findings across cohort years. Direct findings (from analyses based on code tests, module assessment and questionnaire surveys) reveal overall engagement with and high acceptance of collaborative working and of the TEL environments used, but an inconsistent relationship between deeply learned programming skills and module performance. The paper also discusses research findings in the contexts of established and emerging teaching practices for computer programming, as well as government policies and commercial requirements for improved capacity in computer-science related industries

Prevalence of Physical Activity in the United States: Behavioral Risk Factor Surveillance System, 2001

INTRODUCTION: The health benefits of regular cardiovascular exercise are well-known. Such exercise, however, has traditionally been defined as vigorous physical activity, such as jogging, swimming, or aerobic dance. Exercise of moderate intensity also promotes health, and many U.S. adults may be experiencing the health benefits of exercise through lifestyle activities of moderate intensity, such as yard work, housework, or walking for transportation. Until recently, public health surveillance systems have not included assessments of this type of physical activity, focusing on exercise of vigorous intensity. We used an enhanced surveillance tool to describe the prevalence and amount of both moderate-intensity and vigorous-intensity physical activity among U.S. adults. METHODS: We analyzed data from the 2001 Behavioral Risk Factor Surveillance System, a state-based, random-digit–dialed telephone survey administered to U.S. adults aged 18 years and older (n = 82,834 men and 120,286 women). Physical activity behavior was assessed using questions designed to quantify the frequency of participation in moderate- or vigorous-intensity physical activities performed during leisure time or for household chores and transportation. RESULTS: Overall, 45% of adults (48% of men and 43% of women) were active at recommended levels during nonworking hours (at least 30 minutes five or more days per week in moderate-intensity activities, equivalent to brisk walking, or at least 20 minutes three or more days per week in vigorous activities, equivalent to running, heavy yard work, or aerobic dance). Less than 16% of adults (15% of men and 17% of women) reported no moderate or vigorous activity in a usual week. CONCLUSION: Integrating surveillance of lifestyle activities into national systems is possible, and doing so may provide a more accurate representation of the prevalence of recommended levels of physical activity. These results, however, suggest that the majority of U.S. adults are not active at levels associated with the promotion and maintenance of health

Bypass of mutagenic O 6 -Carboxymethylguanine DNA Adducts by Human Y- and B-Family Polymerases

The generation of chemical alkylating agents from nitrosation of glycine and bile acid conjugates in the gastrointestinal tract is hypothesized to initiate carcinogenesis. O6-carboxymethylguanine (O6-CMG) is a product of DNA alkylation derived from nitrosated glycine. Although the tendency of the structurally related adduct O6-methylguanine to code for the misincoporation of TTP during DNA replication is well-established, the impact of the presence of the O6-CMG adduct in a DNA template on the efficiency and fidelity of translesion DNA synthesis (TLS) by human DNA polymerases (Pols) has hitherto not been described. Herein, we characterize the ability of the four human TLS Pols η, ι, κ, and ζ and the replicative Pol δ to bypass O6-CMG in a prevalent mutational hot-spot for colon cancer. The results indicate that Pol η replicates past O6-CMG, incorporating dCMP or dAMP, whereas Pol κ incorporates dCMP only, and Pol ι incorporates primarily dTMP. Additionally, the subsequent extension step was carried out with high efficiency by TLS Pols η, κ, and ζ, while Pol ι was unable to extend from a terminal mismatch. These results provide a first basis of O6-CMG-promoted base misincorporation by Y- and B-family polymerases potentially leading to mutational signatures associated with colon cancer

Qualitative study of system-level factors related to genomic implementation

PURPOSE: Research on genomic medicine integration has focused on applications at the individual level, with less attention paid to implementation within clinical settings. Therefore, we conducted a qualitative study using the Consolidated Framework for Implementation Research (CFIR) to identify system-level factors that played a role in implementation of genomic medicine within Implementing GeNomics In PracTicE (IGNITE) Network projects. METHODS: Up to four study personnel, including principal investigators and study coordinators from each of six IGNITE projects, were interviewed using a semistructured interview guide that asked interviewees to describe study site(s), progress at each site, and factors facilitating or impeding project implementation. Interviews were coded following CFIR inner-setting constructs. RESULTS: Key barriers included (1) limitations in integrating genomic data and clinical decision support tools into electronic health records, (2) physician reluctance toward genomic research participation and clinical implementation due to a limited evidence base, (3) inadequate reimbursement for genomic medicine, (4) communication among and between investigators and clinicians, and (5) lack of clinical and leadership engagement. CONCLUSION: Implementation of genomic medicine is hindered by several system-level barriers to both research and practice. Addressing these barriers may serve as important facilitators for studying and implementing genomics in practice

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism.

International audienceAlthough multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Career progression and the first line manager

Digitised version available at EThOS: British Library Electronic Theses Online Servic