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One in five children in the UK are affected by domestic violence and abuse. However, primary care clinicians (GPs and nurses) struggle to effectively identify and support children and young people living in homes where it is present. The IRIS+ (Enhanced Identification and Referral to Improve Safety) training and advocacy support intervention aimed to improve how clinicians respond to children and young people affected by domestic violence and abuse. IRIS+ training was delivered as part of a feasibility study to four general practices in an urban area in England (UK). Our mixed method design included interviews and questionnaires about the IRIS+ intervention with general practice patients, including children and young people as well as with clinicians and advocacy service providers. We collected the number of identifications and referrals by clinicians of children experiencing domestic violence and abuse through a retrospective search of medical and agency records 10 months after the intervention. Forty-nine children exposed to domestic violence and abuse were recorded in medical records. Thirty-five children were referred to a specialist domestic violence and abuse support service over a period of 10 months. Of these, 22 received direct or indirect support. The qualitative findings indicated that children benefitted from being referred by clinicians to the service. However, several barriers at the patient and professional level prevented children and young people from being identified and supported. Some of these barriers can be addressed through modifications to professional training and guidance, but others require systematic and structural changes to the way health and social care services work with children affected by domestic violence and abuse.  相似文献   
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Dysfunction of immune and vascular systems has been implicated in aging and Alzheimer disease; however, their interrelatedness remains poorly understood. The complement pathway is a well-established regulator of innate immunity in the brain. Here, we report robust age-dependent increases in vascular inflammation, peripheral lymphocyte infiltration, and blood-brain barrier (BBB) permeability. These phenotypes were subdued by global inactivation and by endothelial cell–specific ablation of C3ar1. Using an in vitro model of the BBB, we identified intracellular Ca2+ as a downstream effector of C3a/C3aR signaling and a functional mediator of vascular endothelial cadherin junction and barrier integrity. Endothelial C3ar1 inactivation also dampened microglia reactivity and improved hippocampal and cortical volumes in the aging brain, demonstrating a crosstalk between brain vasculature dysfunction and immune cell activation and neurodegeneration. Further, prominent C3aR-dependent vascular inflammation was also observed in a tau-transgenic mouse model. Our studies suggest that heightened C3a/C3aR signaling through endothelial cells promotes vascular inflammation and BBB dysfunction and contributes to overall neuroinflammation in aging and neurodegenerative disease.  相似文献   
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Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

Methods

Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ–Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.

Results

Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had “deteriorated” status and more had “improved” status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose.

Conclusions

These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population.  相似文献   
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Addition of authors’ affiliation to "Hepatitis B virus detected in paper currencies in a densely populated city of India: A plausible source of horizontal transmission?" World J Hepatol 2020 Oct 27; 12(10): 775-791. In this article, one of the affiliations of two authors was not mentioned. Ruchi Supekar, a joint first author and Subhajit Biswas, the corresponding author are affiliated to Academy of Scientific and Innovative Research (AcSIR) Ghaziabad- 201002, India.  相似文献   
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