15 research outputs found

    The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

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    BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

    An experimental and modeling study of ash deposition behaviour for co-firing peat with lignite

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    Co-firing peat with lignite for power generation was studied at pilot-scale, focusing on the issue of ash deposition, the major concern for this application. A specially designed probe was used to measure the rate of ash deposition under similar conditions of power plant boiler operation. Fraction of peat in the feed was varied up to 100%. It was observed that whereas the ash deposition decreased in general with increasing fraction of low-ash peat, the decrease was significantly less than expected from ash content of the feed, suggesting higher deposition tendency of ash from the peat. Chlorine content in the deposited ash showed a maximum at a certain blend ratio of the feed, which could not be explained by fuel chlorine content alone. The ash and chlorine deposition behaviour has been analyzed and simulated by mathematical models where interactions between fuel chlorine, alkali and ash particles are parameterized. The models ought to be useful for control and optimization purposes, and also be useful for co-firing other fuel blends.Co-firing Peat Fluidized bed Ash deposition Chlorine

    CYP24A1 Exacerbated Activity during Diabetes Contributes to Kidney Tubular Apoptosis via Caspase-3 Increased Expression and Activation

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    <div><p>Decreases in circulating 25,hydroxyl-vitamin D3 (25 OH D3) and 1,25,dihydroxyl-vitamin D3 (1,25 (OH)2 D3) have been extensively documented in patients with type 2 diabetes. Nevertheless, the molecular reasons behind this drop, and whether it is a cause or an effect of disease progression is still poorly understood. With the skin and the liver, the kidney is one of the most important sites for vitamin D metabolism. Previous studies have also shown that CYP24A1 (an enzyme implicated in vitamin D metabolism), might play an important role in furthering the progression of kidney lesions during diabetic nephropathy. In this study we show a link between CYP24A1 increase and senescence followed by apoptosis induction in the renal proximal tubules of diabetic kidneys. We show that CYP24A1 expression was increased during diabetic nephropathy progression. This increase derived from protein kinase C activation and increased H<sub>2</sub>O<sub>2</sub> cellular production. CYP24A1 increase had a major impact on cellular phenotype, by pushing cells into senescence, and later into apoptosis. Our data suggest that control of CYP24A1 increase during diabetes has a beneficial effect on senescence induction and caspase-3 increased expression. We concluded that diabetes induces an increase in CYP24A1 expression, destabilizing vitamin D metabolism in the renal proximal tubules, leading to cellular instability and apoptosis, and thereby accelerating tubular injury progression during diabetic nephropathy.</p> </div

    CYP24A1 is increased 2–3 fold in renal proximal tubules of diabetic mice.

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    <p>mRNA expression levels in renal proximal tubules of mice 20 weeks old were semi-quantified by RT-PCR/PCR, wild type compared to db/db (A) CYP24A1 (a) gel scan, (B) CYP27B1(b) gel scan, (C) VDR (c) gel scan. (*p<0,05; **p<0.01; ***p<0.001). (D) CYP24A1 immuno-staining of paraffin kidney sections (a,c) C57/BL6 wild type 24 weeks old, (b,d) C57/BL6-J <i>db/db</i> 24 weeks old (magnification X200 (a,b), X400 (c,d)).</p

    VDR expression is CYP24A1-dependent and <i>vice-versa</i> CYP24A1 expression is VDR dependent.

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    <p>(A, B and C) CYP24A1 and VDR protein expression analysis by western blotting 4 days after transfection with siRNAs scrambled (control), si<i>CYP24A1</i>, si<i>VDR</i> or pCMV-<i>CYP24A1</i>. (*p<0.05; **p<0.01; ***p<0.001)</p

    CYP24A1, pro-caspase-3, VDR and p27 rise in high fat fed animals, but not in C57/BL6-<i>Cyp24a1 −/−</i> animals high fat fed.

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    <p>(A) Rise and disappearance of Cyp24A1, pro-caspase-3, VDR and p27, in animals after 8 weeks of high fat diet. (B) semi-quantification of CYP24A1 protein expression, (C) semi-quantification of pro-caspase-3 protein expression, (D) semi-quantification of p27 protein expression, (E) semi-quantification of VDR protein expression. (Each group with N = 6–8 animals and *p<0.05; **p<0.01; ***p<0.001)</p

    G1 arrest-induction in high glucose of hPRPTCs is partly CYP24A1-dependent, but apoptosis induction is entirely CYP24A1-dependent.

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    <p>CYP24A1 expression and Caspase-3 activation profiles in hPRPTCs cultured for 4 days under NG or HG and transfected or not with pCMV-<i>CYP24A1</i> (A). hPRPTCs in NG, hPRPTCs in HG, hPRPTC in HG with 10<sup>−9</sup> M Calcitriol, hPRPTCs transfected with pCMV-<i>CYP24A1</i> in NG, hPRPTCs transfected with pCMV-<i>CYP24A1</i> in HG, and hPRPTCs transfected with pCMV-CYP24A1 in HG with 10–6 M Genistein. % of cells in SubG1after 6 days incubation (B), and G1 (C). (*p<0.01; **p<0.05; ***p<0.001)</p

    High Glucose G1 arrest and senescence induction is CYP24A1-dependent.

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    <p>(A) Senescence analysis by SA-βGalactosidase assay after 6 days (a) hPRPTCs in NG, (b) hPRPTCs in HG, (c) hPRPTC after transfection with pCMV-<i>CYP24A1</i> in NG (d) hPRPTC after transfection with pCMV-<i>CYP24A1</i> in HG. (magnification X400). (B) Senescence analysis by SA-βGalactosidase assay after 6 days hPRPTCs after transfection with siRNAs (a) scrambled (control) in NG (b) scrambled (control) in HG and (c) si<i>CYP24A1</i> in HG. (magnification X200). (C) % of senescent cells after 6 days incubation. (D) FACS cell cycle profiles of propidium iodide cell-stained, % of cells in a specific cell cycle phase after 4 days incubation in HG. (*p<0.05; **p<0.01; ***p<0.001)</p

    Control of CYP24A1 high fat fed animals prevents increase of pro-caspase-3 protein expression.

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    <p>(A) Cyp24A1 immuno-staining, proteins (a) C57/BL6 wild type on normo-diet, (b) C57/BL6 wild type on high fat diet, (<b>c</b>) C57/BL6-<i>Cyp24A1 −/−</i> on normo-diet, (d) C57/BL6-<i>Cyp24A1 −/−</i> on high fat diet. (magnification X400). (B) Caspase-3 immuno-staining, proteins (a) C57/BL6 wild type on normo-diet, (b) C57/BL6 wild type on high fat diet, (<b>c</b>) C57/BL6-<i>Cyp24A1 −/−</i> on normo-diet, (d) C57/BL6-<i>Cyp24A1 −/−</i> on high fat diet. (magnification X400). (C) SA-βGalactosidase activity appears in tubular structures of high fat fed animals, but not in C57/BL6-<i>Cyp24a1 −/−</i> animals, as shown by the blue staining. (a) C57/BL6 wild type on normo-diet, (b and e) C57/BL6 wild type on high fat diet, (c) C57/BL6-<i>Cyp24a1 −/−</i> on normo-diet, (d) C57/BL6-<i>Cyp24a1 −/−</i> on high fat diet. (magnification X200 (a,b,c,d) and X400 (e)), (D) Circulating levels of 1,25(OH)2D3 in C57/BL6 wild type and C57/BL6-<i>Cyp24a1 −/−</i> , on either normo or high fat diet, at day of sacrifice (16 weeks) . (Each group with N = 4 animals and *p<0.05; **p<0.01; ***p<0.001)</p
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