964 research outputs found
Bizarre structures in dinosaurs: species recognition or sexual selection? A response to Padian and Horner
Leveraging 3D Technology for Students with Autism: An innovative university-community collaboration for skill development and vocational exploration
This article describes a university-community collaboration in which an inter-professional team partnered to provide students with autism spectrum disorder (ASD) a paid job opportunity to apply 3D modelling skills for a local construction company. Providing meaningful vocational opportunities to improve the transition to adulthood for individuals with ASD is imperative, as individuals with ASD have unemployment rates that are some of the highest of all disabilities. This novel evidence-supported educational program was designed to develop 3D technology skills, explore vocational careers and promote social engagement through shared interests for transition-age youth with ASD. Both parents and students reported many successful outcomes, including increase in student self-confidence, social and technology skill development and the opportunity for vocational exploration by these young people. Implications of the case study are reported in relation to university-community partnerships and the critical role of community collaboration in addressing the high rates of unemployment in individuals with autism
'She's a F**king ticket':the pragmatics of f**k in Irish English - an age and gender perspective
Pharmacokinetics of intravenous sildenafil in children with palliated single ventricle heart defects: effect of elevated hepatic pressures
Abstract Aims Sildenafil is frequently prescribed to children with single ventricle heart defects. These children have unique hepatic physiology with elevated hepatic pressures, which may alter drug pharmacokinetics. We sought to determine the impact of hepatic pressure on sildenafil pharmacokinetics in children with single ventricle heart defects. Methods A population pharmacokinetic model was developed using data from 20 single ventricle children receiving single-dose intravenous sildenafil during cardiac catheterisation. Non-linear mixed effect modelling was used for model development, and covariate effects were evaluated based on estimated precision and clinical significance. Results The analysis included a median (range) of 4 (2–5) pharmacokinetic samples per child. The final structural model was a two-compartment model for sildenafil with a one-compartment model for des-methyl-sildenafil (active metabolite), with assumed 100% sildenafil to des-methyl-sildenafil conversion. Sildenafil clearance was unaffected by hepatic pressure (clearance=0.62 L/hour/kg); however, clearance of des-methyl-sildenafil (1.94×(hepatic pressure/9) −1.33 L/hour/kg) was predicted to decrease ~7-fold as hepatic pressure increased from 4 to 18 mmHg. Predicted drug exposure was increased by ~1.5-fold in subjects with hepatic pressures ⩾10 versus <10 mmHg (median area under the curve=533 versus 792 µg*h/L). Discussion Elevated hepatic pressure delays clearance of the sildenafil metabolite – des-methyl-sildenafil – and increases drug exposure. We speculate that this results from impaired biliary clearance. Hepatic pressure should be considered when prescribing sildenafil to children. These data demonstrate the importance of pharmacokinetic assessments in patients with unique cardiovascular physiology that may affect drug metabolism
Diseño de un instrumento de caracterización de rasgos de personalidad en agresores sexuales
Especial InterésEl objetivo del instrumento es brindar una medida de los rasgos de personalidad predominantes en los agresores sexuales. Gracias a la revisión teórica y empírica, se identificó que se encuentran similitudes en sus rasgos de personalidad, a partir de los cuales se proponen 4 rasgos principales: Narcisista, Obsesivo Compulsivo, Antisocial y Límite de la personalidad. El cuestionario está compuesto por 35 ítems, de tipo dicotómico, que definen los 4 rasgos mencionados, dirigido a población penitenciaria condenada por delito de Agresión Sexual.RESUMEN
1. JUSTIFICACIÓN
2. MARCO LEGAL
3. MARCO ÉTICO
4. OBJETIVOS
5. PRODUCTO VISIBLE
6. ESTUDIO DE MERCADEO
7. El PRODUCTO
RESULTADOS
DISCUSIÓNPregradoPsicólog
Maternal Drinking During Pregnancy: Attention and Short-Term Memory in 14-Year-Old Offspring—A Longitudinal Prospective Study
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66151/1/j.1530-0277.1994.tb00904.x.pd
FAD binding, cobinamide binding and active site communication in the corrin reductase (CobR)
Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. The aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before adenosylation can take place. A corrin reductase (CobR) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin dinucleotide) and we also show that the enzyme can bind a corrin substrate consistent with its role in reduction of the cobalt of the corrin ring. Stopped-flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides a potential link between the two electron reduction by NADH to the single electron reduction of Co(II) to Co(I)
Study Protocol: The Behaviour and Pain in Dementia Study (BePAID)
<p>Abstract</p> <p>Background</p> <p>People with dementia admitted to the acute hospital often receive poor quality care particularly with regards to management of behavioural and psychiatric symptoms of dementia (BPSD) and of pain. There have been no UK studies on the prevalence and type of pain or BPSD in people with dementia in this setting, or on how these may impact on patients, carers, staff and costs of care.</p> <p>Methods/Design</p> <p>We shall recruit older people with dementia who have unplanned acute medical admissions and measure the prevalence of BPSD using the Behave-AD (Behaviour in Alzheimer's Disease) and the CMAI (Cohen Mansfield Agitation Inventory). Pain prevalence and severity will be assessed by the PAINAD (Pain Assessment in Advanced Dementia) and the FACES pain scale. We will then analyse how these impact on a variety of outcomes and test the hypothesis that poor management of pain is associated with worsening of BPSD.</p> <p>Discussion</p> <p>By demonstrating the costs of BPSD to individuals with dementia and the health service this study will provide important evidence to drive improvements in care. We can then develop effective training for acute hospital staff and alternative treatment strategies for BPSD in this setting.</p
Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B
Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone
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