195 research outputs found

    Impact of Scottish vocational qualifications on residential child care : have they fulfilled the promise?

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    This article will present findings from a doctoral study exploring the impact of 'SVQ Care: Promoting Independence (level III)' within children's homes. The study focuses on the extent to which SVQs enhance practice and their function within a 'learning society'. A total of 30 staff were selected from seven children's homes in two different local authority social work departments in Scotland. Each member of staff was interviewed on four separate occasions over a period of 9 months. Interviews were structured using a combination of repertory grids and questions. Particular focus was given to the assessment process, the extent to which SVQs enhance practice and the learning experiences of staff. The findings suggest that there are considerable deficiencies both in terms of the SVQ format and the way in which children's homes are structured for the assessment of competence. Rather than address the history of failure within residential care, it appears that SVQs have enabled the status quo to be maintained whilst creating an 'illusion' of change within a learning society

    School violence, school differences and school discourses

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    This article highlights one strand of a study which investigated the concept of the violenceresilient school. In six inner-city secondary schools, data on violent incidents in school and violent crime in the neighbourhood were gathered, and compared with school practices to minimise violence, accessed through interviews. Some degree of association between the patterns of behaviour and school practices was found: schools with a wider range of wellconnected practices seemed to have less difficult behaviour. Interviews also showed that the different schools had different organisational discourses for construing school violence, its possible causes and the possible solutions. Differences in practices are best understood in connection with differences in these discourses. Some of the features of school discourses are outlined, including their range, their core metaphor and their silences. We suggest that organisational discourse is an important concept in explaining school effects and school differences, and that improvement attempts could have clearer regard to this concept

    Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records

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    Introduction: To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Methods: Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997–2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Results: Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67–43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69–10.85]), heart failure (4.31, [3.30–5.62]), and atrial fibrillation (3.80 [3.04–4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27–2.84]) and coronary revascularisation (2.32 [1.46–3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Conclusions: Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases

    Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways

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    <p>Abstract</p> <p>Background</p> <p>Up-regulation of vascular endothelin type B (ET<sub>B</sub>) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, <it>ex vivo</it>, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ET<sub>B </sub>receptors in human internal mammary arteries.</p> <p>Methods</p> <p>Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using <it>in vitro </it>pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ET<sub>A </sub>and ET<sub>B </sub>receptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists.</p> <p>Results</p> <p>The endohtelin-1-induced contraction (after endothelin ET<sub>B </sub>receptor desensitization) and the endothelin ET<sub>A </sub>receptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ET<sub>B </sub>receptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 μM bisindolylmaleimide I and 10 μM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 μM SB203580, 10 μM PD98059 and 10 μM SP600125, respectively).</p> <p>Conclusion</p> <p>In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ET<sub>B </sub>receptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ET<sub>B </sub>receptor changes in cardiovascular disease.</p

    Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

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    <p>Abstract</p> <p>Background</p> <p>Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease.</p> <p>Methods</p> <p>Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ET<sub>A</sub>) and type B (ET<sub>B</sub>), and angiotensin type 1 (AT<sub>1</sub>) and type 2 (AT<sub>2</sub>) receptors expression and function were examined using immunohistochemistry, Western blot and <it>in vitro </it>pharmacology.</p> <p>Results</p> <p>ET<sub>A </sub>and, to a lesser extent, ET<sub>B </sub>receptor staining was observed in the healthy vascular smooth muscle cells. The level of ET<sub>B </sub>receptor expression was higher in patients undergoing CABG surgery (250% ± 23%; P < 0.05) and in the patients with angina pectoris (199% ± 6%; P < 0.05), than in the healthy controls (100% ± 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ET<sub>B </sub>receptor agonist sarafotoxin S6c, compared to healthy controls (P < 0.05). No such difference was found for the ET<sub>A </sub>receptors. AT<sub>1 </sub>and, to a lesser extent, AT<sub>2 </sub>receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT<sub>1 </sub>receptor expression was higher in both the angina pectoris (128% ± 25%; P < 0.05) and in the CABG patients (203% ± 41%; P < 0.05), as compared to the healthy controls (100% ± 25%). The increased AT<sub>1 </sub>receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s).</p> <p>Conclusion</p> <p>The results demonstrate, for the first time, upregulation of ET<sub>B </sub>and AT<sub>1 </sub>receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions.</p

    Stochastic Population Forecasting Based on Combinations of Expert Evaluations Within the Bayesian Paradigm

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    The paper suggests a procedure to derive stochastic population forecasts adopting an expert-based approach. As in a previous work by Billari et al. (2012), experts are required to provide evaluations, in the form of conditional and unconditional scenarios, on summary indicators of the demographic components determining the population evolution, i.e. fertility, mortality and migration. Here two main purposes are pursued. First, the demographic components are allowed to have some kind of dependence. Second, as a result of the existence of a body of shared information, possible correlations among experts are taken into account. In both cases, the dependence structure is not imposed by the researcher but it is indirectly derived through the scenarios elicited from the experts. To address these issues, the method is based on a mixture model, within the so-called Supra-Bayesian approach according to which expert evaluations are treated as data. The derived posterior distribution for the demographic indicators of interest is used as forecasting distribution and a Markov Chain Monte Carlo algorithm is designed to approximate this posterior. The paper provides the questionnaire which was designed by the authors to collect expert opinions. Finally, an application to the forecast of the Italian Population from 2010 up to 2065 is proposed

    Adam Smith and Competitive Equilibrium

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    A view has emerged which sees Adam Smith’s main contribution to economics in terms of his equilibrium theory. This paper argues that equilibrium economics was neither Smith’s main contribution nor his chief concern. It is true that Smith made a few observations which may be construed as equilibrium economics in some loose sense. For example, his observation that the market price of a commodity has a tendency to gravitate towards its natural price; or the rate of profit in different employments tends towards equality. But from this it cannot be concluded that Smith was chiefly an equilibrium theorist. In the first place, it needs to be emphasised that the ‘tendency’ towards equilibrium, which Smith talked about, is not the same thing as an equilibrium ‘outcome’. Equilibrium as an outcome is more likely to be reached in a stationary state than in an evolutionary system in the process of continuous dynamic motion. Smith’s evolutionary perspective, his analysis of the division of labour, capital accumulation, and the institutions most conducive to the generation of wealth, all point to the fact that Smith was more concerned with dynamic analysis than with static equilibrium. Finally, barring a few observations on the equilibrating tendency in the system, most of the Wealth of Nations is not devoted to this question

    Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

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    Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research
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