13,443 research outputs found

    ATP-Sensitive Potassium Channel-Mediated Lactate Effect on Orexin Neurons: Implications for Brain Energetics during Arousal

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    Active neurons have a high demand for energy substrate, which is thought to be mainly supplied as lactate by astrocytes. Heavy lactate dependence of neuronal activity suggests that there may be a mechanism that detects and controls lactate levels and/or gates brain activation accordingly. Here, we demonstrate that orexin neurons can behave as such lactate sensors. Using acute brain slice preparations and patch-clamp techniques, we show that the monocarboxylate transporter blocker Îą-cyano-4-hydroxycinnamate (4-CIN) inhibits the spontaneous activity of orexin neurons despite the presence of extracellular glucose. Furthermore, fluoroacetate, a glial toxin, inhibits orexin neurons in the presence of glucose but not lactate. Thus, orexin neurons specifically use astrocyte-derived lactate. The effect of lactate on firing activity is concentration dependent, an essential characteristic of lactate sensors. Furthermore, lactate disinhibits and sensitizes these neurons for subsequent excitation. 4-CIN has no effect on the activity of some arcuate neurons, indicating that lactate dependency is not universal. Orexin neurons show an indirect concentration-dependent sensitivity to glucose below 1mM, responding by hyperpolarization, which is mediated by ATP-sensitive potassium channels composed of Kir6.1 and SUR1 subunits. In conclusion, our study suggests that lactate is a critical energy substrate and a regulator of the orexin system. Together with the known effects of orexins in inducing arousal, food intake, and hepatic glucose production, as well as lactate release from astrocytes in response to neuronal activity, our study suggests that orexin neurons play an integral part in balancing brain activity and energy supply

    Bonne Bay-A Treasure and a Resource

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    Investigation Into Laser Shock Processing

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    Laser shock processing is a good candidate for surface industry due to its rapid processing, localized ablation, and precision of operation. In the current study, laser shock processing of steel was considered. The numerical solutions for temperature rise and recoil pressure development across the interface of the ablating front and solid are presented. The propagation of elastic-plastic waves in the solid due to recoil pressure loading at the surface is analyzed and numerical solution for the wave propagation was obtained. An experiment was conducted to ablate the steel surfaces for shock processing. Scanning electron microscopy was carried out to examine the ablated surfaces shock processing while transmission electron microscopy was conducted to obtain dislocation densities after the shock processing. It was found that surface hardness of the workpiece increased in the order of 1.8 times of the base material hardness, and the dislocation was the main source of the shock hardening in the region affected by laser shock processing

    Miniaturized data loggers and computer programming improve seabird risk and damage assessments for marine oil spills in Atlantic Canada

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    Obtaining useful information on marine birds that can aid in oil spill (and other hydrocarbon release) risk and damage assessments in offshore environments is challenging. Technological innovations in miniaturization have allowed archival data loggers to be deployed successfully on marine birds vulnerable to hydrocarbons on water. A number of species, including murres (both Common, Uria aalge, and Thick-billed, U. lomvia) have been tracked using geolocation devices in eastern Canada, increasing our knowledge of the seasonality and colony-specific nature of their susceptibility to oil on water in offshore hydrocarbon production areas and major shipping lanes. Archival data tags are starting to resolve questions around behaviour of vulnerable seabirds at small spatial scales relevant to oil spill impact modelling, specifically to determine the duration and frequency at which birds fly at sea. Advances in data capture methods using voice activated software have eased the burden on seabird observers who are collecting increasingly more detailed information on seabirds during ship-board and aerial transects. Computer programs that integrate seabird density and bird behaviour have been constructed, all with a goal of creating more credible seabird oil spill risk and damage assessments. In this paper, we discuss how each of these technological and computing innovations can help define critical inputs into seabird risk and damage assessments, and when combined, can provide a more realistic understanding of the impacts to seabirds from any hydrocarbon release

    The Potential for Telehealth Consultations in Cardiology and Dermatology in Newfoundland and Labrador: A Synthesis of Research Evidence

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    This report provides a synthesis of relevant research evidence on the clinical and cost effectiveness of telehealth technologies for specialist-patient consultations in the fields of cardiology and dermatology. The report is intended to inform and assist decision makers in the Labrador-Grenfell Regional Health Authority, the Newfoundland and Labrador Department of Health and Community Services and the province’s other Regional Health Authorities by providing research evidence surrounding the effectiveness of telehealth consultation as an intervention for cardiology or dermatology patients. The findings of our synthesis are specifically interpreted for the context of Newfoundland and Labrador. Decision makers from other jurisdictions, particularly those with similar features in terms of potential clients, geography and resources, may also find the content helpful. The report includes explanations of research terms and technical language; as such, there is no need to have a specialized medical or health background to understand its content

    Public perceptions of drinking water: A postal survey of residents with private water supplies

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    Background: In Canada, the legal responsibility for the condition of private water supplies, including private wells and cisterns, rests with their owners. However, there are reports that Canadians test these water supplies intermittently and that treatment of such water is uncommon. An estimated 45% of all waterborne outbreaks in Canada involve non-municipal systems. An understanding of the perceptions and needs of Canadians served by private water supplies is essential, as it would enable public health professionals to better target public education and drinking water policy. The purpose of this study was to investigate the public perceptions of private water supplies in the City of Hamilton, Ontario (Canada), with the intent of informing public education and outreach strategies within the population. Methods: A cross-sectional postal survey of 246 residences with private water supplies was conducted in May 2004. Questions pertained to the perceptions of water quality and alternative water sources, water testing behaviours and the self-identified need for further information. Results: Private wells, cisterns or both, were the source of household water for 71%, 16% and 13% of respondents, respectively. Although respondents rated their water quality highly, 80% also had concerns with its safety. The most common concerns pertained to bacterial and chemical contamination of their water supply and its potential negative effect on health. Approximately 56% and 61% of respondents used in-home treatment devices and bottled water within their homes, respectively, mainly due to perceived improvements in the safety and aesthetic qualities compared to regular tap water. Testing of private water supplies was performed infrequently: 8% of respondents tested at a frequency that meets current provincial guidelines. Two-thirds of respondents wanted more information on various topics related to private water supplies. Flyers and newspapers were the two media reported most likely to be used. Conclusion: Although respondents rated their water quality highly, the majority had concerns regarding the water from their private supply, and the use of bottled water and water treatment devices was extensive. The results of this study suggest important lines of inquiry and provide support and input for public education programs, particularly those related to private water testing, in this population

    Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

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    A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, ι = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, ι = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, ι = 0.29; dominant HLOD = 3.03, ι = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, ι = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. Š 2012 Cicek et al

    Mobile Mental Health Crisis Intervention in the Western Health Region of Newfoundland and Labrador

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    The impetus for this research is Recommendation #15 of the 2003 Luther Inquiry into the deaths of Norman Reid and Darryl Power: “IT IS FURTHER RECOMMENDED that the Regional Health Boards establish mobile health units to respond to mentally ill persons in crisis where no criminal offence is alleged. Each unit would be developed locally and based on local needs.” Our stakeholder partners in the Western Regional Health Authority asked us to identify a range of mobile crisis intervention service models, some of which may be better suited to lower-density, rural populations and some of which may be better suited to higher-density areas like Corner Brook. Our partners expressed a particular interest in models that can be implemented with minimal additional human resources, but that involve local, face-to-face contact rather than telephone, electronic, or clinic-based models of service delivery. The term “crisis intervention” generally refers to any immediate, short-term therapeutic interventions or assistance provided to an individual or group of individuals who are in acute psychological distress or crisis. The term encompasses a number of after-the-fact interventions – such as rape counseling and critical incident stress debriefing – that would not be relevant to the kinds of situations described in the Luther Report. Given the project parameters specified by our partners at Western Health, we formulated a research question and a literature search strategy that would enable us to focus specifically on forms of crisis intervention that are designed to manage potentially dangerous mental health crises on-site rather than to mediate their impacts after the fact. Our research question is as follows: “What models of mobile– i.e., face-to-face – crisis intervention have proven effective in managing potentially violent mental health crises occurring outside the hospital setting?

    Seasonal variation of the three-dimensional mean circulation over the Scotian Shelf

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    The seasonal-mean circulation over the Scotian Shelf is studied numerically by computing mean and tidal current fields for winter, spring, and summer using a three-dimensional nonlinear diagnostic model. The mean current fields are forced by seasonal-mean baroclinic pressure gradients, tidal rectification, uniform wind stresses, and associated barotropic pressure gradients. A historical hydrographic database is used to determine the climatological mean baroclinic forcing. Upstream open boundary conditions are estimated from the density fields to give no normal geostrophic bottom flow and are specified as either along-boundary elevation gradients or depth-integrated normal velocities. The numerical solutions for nominal bimonthly periods (January–February, April–May, and July–August) reveal the dominant southwestward nearshore and shelf-break flows of relatively cool and fresh shelf water from the Gulf of St. Lawrence and Newfoundland Shelf, with speeds up to about 20 cm/s. The seasonal intensification of the southwestward flows is reproduced by the model, with the transport increasing from 0.3 Sv in summer to 0.9 Sv in winter on the inner Halifax section. There are also pronounced topographic-scale influences of submarine banks, basins, and cross-shelf channels on the circulation, such as anticyclonic gyres over banks and cyclonic gyres over basins. Baroclinicity is the dominant forcing throughout the domain, but tidal rectification is comparable on the southwestern Scotian Shelf (e.g., about 0.2 Sv recirculating transport around Browns Bank for all the periods). The mean wind stress generates offshore surface drift in winter. The solutions are in approximate agreement with observed currents and transports over the Scotian Shelf, although there are local discrepancies
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