共查询到20条相似文献，搜索用时 15 毫秒
1.
Background
Reporting of the incidence of child maltreatment by parents and children might differ with implications for optimum research methodologies to determine the incidence of maltreatment. Our aim was to compare parent and child reports of child maltreatment in mainland China.Methods
A cross-sectional study was done in two primary schools and two secondary schools in urban and rural Zhejiang Province. Children aged 10–16 years and their parents completed a questionnaire survey. The same questions about child maltreatment appeared in both parent and child questionnaires and included 38 disciplinary acts (21 physical, 12 emotional, and five, non-contact). Parent–child pairs from the same household were matched to compare parent–child reports of maltreatment. We used McNemar's χ2 test and Cohen's kappa coefficient for the statistical analysis. The study was approved by University College London and Zhejiang University Research Ethics Committees. All participants gave informed consent.Findings
Questionnaires were completed by 611 parents and 821 children, with 324 mother–child pairs and 235 father–child pairs. For mother–child pairs, the lifetime prevalences of maltreatment (mothers vs their children) were 53·4% versus 36·7% for physical acts; 76·2% versus 50·0% for emotional acts; and 19·4% versus 13·0% for non-contact acts. For father–child pairs, the lifetime prevalences of maltreatment (fathers vs their children) were 57·9% versus 39·0% for physical acts; 71·5% versus 44·3% for emotional acts; and 22·6% versus 16·2% for non-contact acts. The prevalence of emotional maltreatment in the previous year was reported more by parents than children (55·9% mothers vs 32·7% children; 54·0% fathers vs 31·5% children), with no differences for physical maltreatment and non-contact punishment. The Cohen's kappa coefficients ranged from 0·09 to 0·39, indicating low agreement between parent–child reports.Interpretation
High levels of child maltreatment are common in China. To gain accurate figures for maltreatment, both children and caregivers should be considered in research. Consistently lower figures in children might relate to recall bias or acceptance of acts of maltreatment as normal. Parents readily admit maltreating their children, possibly indicating its normalisation in China, indicating the need for parenting education.Funding
China Scholarship Council and Universities' China Committee in London. 相似文献2.
Aravinthan Varatharaj Maria Liljeroth Stig Cramer Charlotte Stuart Elina Zotova Angela Darekar Henrik Larsson Ian Galea 《Lancet》2017
Background
Systemic inflammation can affect disease expression in multiple sclerosis. The mechanism might involve blood–brain barrier disruption. We aimed to assess the effects of systemic inflammation on disease progression in multiple sclerosis and the role of blood–brain barrier disruption.Methods
We recruited adults with relapsing–remitting multiple sclerosis and healthy controls from the general population. Three-dimensional dynamic-contrast enhanced MRI was used to measure blood–brain barrier permeability in the normal-appearing white matter (NAWM). Urinary neopterin, a product of activated macrophages, was measured to provide a readout of systemic inflammation. All study activities were performed in University Hospital Southampton after ethics approval (REC 12/SC/0176).Findings
12 patients with mutliple sclerosis and 12 healthy controls were recruited. Blood–brain barrier permeability in NAWM, measured as the constant Ktrans, was significantly higher in patients than in controls (mean 0·024 ml/100g per min [SD·0·018] vs 0·006 [0·004], p=0·015). Systemic inflammatory activity, measured as the urinary neopterin:creatinine ratio (UNCR), was also significantly higher (3·35 [1·98] vs 1·36 [0·29], p=0·002). Across all participants, there was a weak positive correlation between Ktrans and UNCR (r=0·40, p=0·031).Interpretation
Our findings support the hypothesis that the effects of systemic inflammation on expression of multiple sclerosis disease are mediated by blood–brain barrier disruption. Targeting this disruption and systemic inflammation might provide novel avenues for disease-modifying therapy.Funding
University of Southampton, National Institute for Health Research, Multiple Sclerosis Society. 相似文献3.
Background
Coronary artery bypass graft (CABG) surgery is one of the major surgeries requiring long-term stay in hospital. This generally leads to the detrimental effects of bed-rest, including dependency in self-care, transfer, and locomotion. Our aim was to compare the effect of high-frequency and low-frequency exercise therapy in patients who had undergone CABG.Methods
Patients who had undergone CABG were recruited from PSG Medical College and Hospital, Coimbatore, India, between Jan 1 and March 31, 2006. Functional Independence Measure (FIM) and modified Borg Rating of Perceived Exertion (RPE) were used to assess functional outcome. In a quasi-experimental design, patients received either high-frequency exercise therapy (exercise three times a day for 10 days, group 1), or low-frequency exercise therapy (once a day for 10 days, group 2). Data were analysed with paired t tests.Findings
30 patients were recruited (15 in each group). Mean FIM was 75 (SD 1·77) in group 1 and 64 (1·65) in group 2. There was a significant difference between the pretest and post-test FIM values in group 1 patients (49·07 [2·43] vs 124·07 [1·75], p<0·0001) but not in group 2 patients. The RPE in group 1 and group 2 was 6·3 (0·62) and 4·2 (0·7), respectively.Interpretation
Patients given high-frequency exercise thearpy had a significant improvement in their physical activity, but low-frequency exercise did not lead to significantly improved changes. In conclusion, the high-frequency exercise therapy improves the functional ability of patients with CABG.Funding
None. 相似文献4.
Background
In 2013, the authors of the World Alzheimer Report estimated that 44·35 million people had dementia worldwide, causing a substantial economic cost for the society. Objective, systematic economic costs caused by dementia are needed to track disease burden and inform health policy. We aimed to estimate the global economic burden of dementia by country and regions.Methods
We searched PubMed, Google Scholar, Web of Science, the China National Knowledge Infrastructure Database, and Wanfang databases for studies of the economic costs of Alzheimer's disease and other forms of dementia that were published between Jan 1, 2000, and April 1, 2017. On the basis of the scienti?c literature and regressions, we used the latest dementia prevalence estimates from the 2013 World Alzheimer's Disease Report and several other data sources to estimate the economic costs of dementia by setting for different countries and regions.Findings
Our global estimates suggest that the total economic costs caused by dementia increased from US$279·6 billion in 2000 to $948 billion in 2016, with an annual growth rate of 15·94%. This included costs of informal care at $95·1 billion in 2000 and $401·9 billion in 2016, with the annual growth rate of 21·50%. Regional differences in the economic burden of dementia exist, and the highest economic burden was found in Europe and North America.Interpretation
Our ?ndings suggest that dementia is a substantial economic burden worldwide. A global and regional strategic action plan for dementia will be important to reduce the future burden of dementia.Funding
Tsinghua University Education Foundation (Global Health Program, 16-263). 相似文献5.
Background
Hepatitis B-related liver cirrhosis and hepatocellular carcinoma is a serious problem in China. Radiofrequency ablation had been considered a good option because it is minimally invasive. The aim of this study was to compare the perioperative outcomes of laparoscopic liver resection (LLR) with percutaneous radiofrequency ablation (RFA) for patients with hepatocellular carcinoma patients.Methods
A retrospective analysis of a prospective database for liver tumours identified patients with liver cirrhosis who underwent LLR and RFA of hepatocellular carcinoma in the University of Hong Kong, Queen Mary Hospital, Hong Kong between March 18, 2002, and Nov 23, 2015. The complications and-long term outcome after the operations were compared.Findings
We identified 217 patients who underwent laparoscopic treatment of hepatocellular carcinoma with liver cirrhosis in the University of Hong Kong, Queen Mary Hospital, between 2000 and 2015. 112 patients had undergone percutaneous RFA, and 105 patients who had undergone LLR with similar were selected for comparison. The patient baseline parameters, including age, sex, comorbidity, tumour size, number, and stage of hepatocellular carcinoma, did not differ between patients in the LLR and RFA groups. The median number of tumours was one tumour per patient in both treatment groups (range 1–3; p=0·517). Patients in the RFA group and LLR group had similar duration of hospital stay (2 days vs 4 days, p<0·0001), morbidity (4·5% vs 9·5%, p=0·142), and mortality (0% vs 0%). Intrahepatic recurrence was 70·5% in the RFA group versus 28·6% in the LLR group (p<0·0001). RFA was associated with the lowest overall survival (90·8 months in the RFA group vs >146·4 months in the LLR group, p=0·00019) and lowest disease-free survival (16·9 months vs 74·9 month; p<0·0001).Interpretation
LLR and RFA are well tolerated in patients with liver cirrhosis. A better survival outcome has been observed in the LLR group. We suggest LLR be considered as an option in selected patients who are deemed poor candidates for open hepatectomy.Funding
None. 相似文献6.
Background
Mitochondrial DNA damage has been implicated in atherosclerosis but whether it is sufficient to induce mitochondrial dysfunction is unclear. Here we investigated the bioenergetics of human atherosclerotic plaques and the effects of atherogenic lipids on mitochondrial respiration and turnover in vascular smooth muscle cells (VSMCs).Methods
Human atherosclerotic plaques derived from patients undergoing carotid endarterectomy were dissected into defined regions including healthy media, shoulder region, fibrous cap, and core. Their bioenergetic profiles were investigated with an extracellular flux analyser (Seahorse, Agilent Technologies, Santa Clara, CA, USA). VSMCs derived from rat or human aortas were treated with oxidised LDL (OxLDL) before extracellular flux analysis and assessment of mitophagy using the mitochondrially targeted keima reporter.Findings
The basal oxygen consumption rate was similar across human atherosclerotic regions (five plaques, 25 samples per region). However, respiration after uncoupling with p-(tri-fluromethoxy)phenyl-hydrazone (FCCP) was significantly induced in the healthy media (mean 210% of baseline [SD 53], p=0·0017) and shoulder region (169% [47], p=0·0048) but not in the diseased fibrous cap (128% [43], p=0·15) or core (127% [32], p=0·10) regions. OxLDL decreased basal respiration in a dose-dependent manner (OxLDL at 100 μg/mL concentration mean 7·0 pmol/min per μg protein [SD 2·17] vs control 10·10 [2·86], p<0·0001), and FCCP induced respiration of rat VSMCs (8·60 [3·37] vs 14·10 [5·21], p<0·0001) and induced mitophagy in human VSMCs (0·43 arbitrary units [0·20] vs 0·15 [0·18], p=0·0007).Interpretation
We show that mitochondrial damage in human atherosclerotic plaques is sufficient to affect their function. Atherogenic lipids cause changes in mitochondrial metabolism and induce mitophagy in human VSMCs. Knowledge of the role of mitochondrial bioenergetics and turnover is important for our understanding of disease progression and could lead to future therapeutic targets.Funding
Wellcome Trust, British Heart Foundation, Medical Research Council. 相似文献7.
Background
Cancer cell plasticity, as seen in epithelial-to-mesenchymal transition, can lead to metastasis and therapeutic failure. Another cell type, the amoeboid, has now been isolated in oral cancer. Previously seen in, but not isolated from melanomas and sarcomas, it has been associated with poorer prognosis. The aim of the study was to investigate the role of the amoeboid cell in oral cancer, with the hypothesis that it is a plastic, but more invasive and chemoresistant, cell type.Methods
In this in-vitro study of oral cancer cell lines (n=6), fresh tumour specimens, and mice, we used high-throughput invasion assays, migration and drug response assays, protein and gene expression profiling, mechanistic and pathway analysis, fluorescence-activated cell sorting, gene knockdowns, and immunostaining. At least three cell lines were used for each laboratory technique, with a minimum of triplicate repeats and appropriate statistical analysis.Findings
In all cell lines, amoeboid cells were smaller than both epithelial and mesenchymal cells (median cell area 295 μm2 [IQR 218–399] vs 884 [573–1281] vs 598 [413–815]) but were significantly more migratory with a mean velocity of 1·1 μm/min (SD 0·2) versus 0·16 (0·08) for mesenchymal cells (p<0·0001). Amoeboid cells were four to 20 times more invasive than other cell types (p<0·0001). Greater chemoresistance was demonstrated against common agents including paclitaxel and etoposide. Gene analysis produced signatures associated with angiogenesis, anti-apoptosis, and invasion. Stemness genes were upregulated. Plasticity between phenotypes was clearly seen.Interpretation
We describe a new amoeboid cell phenotype, which is derived from epithelial cancer cells, that might confer upon carcinomas a greater ability to invade, disseminate, and resist therapy. A switch to an amoeboid phenotype could be a useful escape strategy for cancers, providing them with alternative modes for migration and invasion. However, this cell type essentially lacks keratin, which could complicate histopathological assessment of tumour spread. Pathway elucidation might yield new potential amoeboid targets. Targeting amoeboid cells, which may now become possible with their isolation and analysis, could be essential to improve patient outcomes.Funding
Royal College of Surgeons of England, British Association of Oral and Maxillofacial Surgeons, Facial Surgery Research Foundation, Faculty of Dental Surgeons (Royal College of Surgeons of England). 相似文献8.
Background
Sarcopenia is a common geriatric disorder characterised by progressive loss of muscle, strength, and function. The prevalence of sarcopenia among elderly people in the Chinese elderly population is increasing and is associated with high rates of frailty, comorbidities, and premature mortality. The prevalence of sarcopenia in China has been reported in many observational studies; however, the estimated prevalence varies within a certain range because no consensus on definition exists. We did a systematic review and meta-analysis to assess the sarcopenia prevalence in community-dwelling people aged 60 years and older in the Chinese population.Methods
In accordance with MOOSE and PRISMA guidelines, we searched PubMed, MEDLINE, Embase, ISI Web of Knowledge, and the Chinese WanFang database for observational community-dwelling studies published before March 12, 2017, without language restrictions. Studies were considered eligible if (1) they reported the prevalence of sarcopenia among Chinese elderly people at least 60 years of age, and (2) they used any of the following criteria for sarcopenia diagnosis: the Asian Working Group for Sarcopenia (AWGS), the European Working Group on Sarcopenia in Older People (EWGSOP), and the International Working Group on Sarcopenia (IWGS) criteria. We assessed prevalence of sarcopenia in random effects model by applying the logit transformation for prevalence proportions extracted from included studies, and pooled logit prevalence estimates were then back-transformed to their original scale for ease interpretation. We also did a subgroup analysis to determine the effect of sex and diagnostic criterion on prevalence.Findings
We included 17 observational studies in the systematic review and meta-analysis. Of the 18?841 participants in total, 2436 participants (11%) had sarcopenia (95% CI 7·8–14·61%). We found significant heterogeneity between individual studies (I2=98·27%; p<0·0001) but no indication of publication bias (p=0·7765). Results of a subgroup analysis showed that Chinese elderly men had about 1·5 times higher prevalence estimates than women (14%; 95% CI 9·68–19·11% vs 9·11%; 6·48–12·67%). The occurrence rate of AWGS-defined sarcopenia was 8% (7·00–9·80%), which is slightly lower than that based on the EWGSOP criterion (10%; 6·54–14·06%), but the prevalence increased to 20% (15·9–25·69%) according to the IWGS criterion.Interpretation
This meta-analysis is the first to provide a comprehensive overview of the burden of sarcopenia among community-dwelling elderly people in China. Our results suggest a high prevalence irrespective of sex and diagnostic definition. Our findings also emphasise the urgent need for therapeutic interventions and preventive management of sarcopenia because of a rapidly ageing population in China.Funding
None. 相似文献9.
10.
Background
Radiotherapy is an essential treatment component for patients with stage III non-small-cell lung cancer. Despite advances, survival remains poor. Proton beam therapy holds the promise of improving cure rates without increasing treatment-related toxicity. However, precision in dose delivery is sensitive to setup uncertainties. The conventional method of adding a margin to account for this problem can be inadequate. We aimed to use the probabilistic scenarios methodology to assess the robustness of intensity modulated proton therapy (IMPT) and volumetric arc therapy (VMAT).Methods
Plans were optimised by minimax robust optimisation (MM) and margin-based (planning target volume [PTV]) methods (MM–IMPT, PTV–IMPT, and VMAT). Robustness was assessed with probabilistically simulated setup errors. 35 perturbed doses were summed to model a treatment course. The CTV-D98 (dose to 98% of the clinical target volume) of each summed dose distribution was compared with the nominal plan and considered robust if within 5%. The variance of the CTV-D98 in IMPT and VMAT plans were compared using Levene's Test.Findings
700 simulations from 20 plans were analysed. Despite dose variation over a simulated course of treatment, the robustness of each summed plan was within clinical limits. There was significantly less variance in the perturbed CTV-D98 in the MM–IMPT than in PTV–IMPT plans (4·43 cGy2vs 16·17, F=50·993, p<0·0001). There was no statistically significant difference between the variance in VMAT and MM–IMPT plans (2·23 cGy2vs 4·04, F=0·312, p=0·577). Target conformality improved with increasing number of beams and robust optimisation. All summed plans met normal tissue dose constraints.Interpretation
Initial results showed that fractionation reduced uncertainties in dose distribution due to setup errors. Robustness of MM–IMPT and VMAT plans were similar. Although the present analysis has not considered range uncertainties and organ motion, the simulations highlight differences in plan qualities with different optimisation strategies. The probabilistic scenarios methodology might be used to estimate robustness of IMPT plans in stage III non-small-cell lung cancer.Funding
Cancer Research UK. 相似文献11.
Carol Kan Jonathan Coleman Anubha Mahajan Mark McCarthy Gerome Breen Khalida Ismail Cathryn Lewis 《Lancet》2017
Background
A genetic overlap between type 2 diabetes and depression has been reported in twin studies, but the finding has not been replicated with data from genome-wide association studies. Visceral adiposity has been postulated as being on the causal pathway of the association between type 2 diabetes and depression. Since waist-to-hip ratio can be a proxy measure of intra-abdominal fat deposition, we examined its effect on the association using the polygenic scores approach in the UK Biobank.Methods
Type 2 diabetes polygenic scores were constructed from the association summary statistics of the Diabetes Genetic Replication And Meta-analysis Consortium, and depression polygenic scores from the Psychiatric Genetics Consortium Major Depressive Disorders Workgroup (29 studies at seven association p-value thresholds [p=0·001 to p=0·5). Logistic regression examined the association between type 2 diabetes polygenic scores and depression case-control status and the effect of body-mass index (BMI)-adjusted waist-to-hip ratio on the association, adjusting for ancestry, centres, and genotyping batches.Findings
The UK Biobank sample with genotyping data consisted of 152?551 participants. There were 10?005 cases and 19?314 controls for depression among individuals of European ancestry, with a mean age of 57·1 years (SD 7·8), BMI of 27·5 kg/m2 (4·7), and waist-to-hip ratio of 0·88 (0·09). Type 2 diabetes polygenic scores were not predictive of depression case-status at all p-value thresholds examined. The interaction between waist-to-hip ratio and type 2 diabetes polygenic scores had an effect on depression case-status (at p-value threshholds <0·2, β=0·37, p=0·02).Interpretation
Our exploratory study tentatively suggests that waist-to-hip ratio might have a role in the effect of type 2 diabetes polygenic scores on depression case-status. Higher adiposity is associated with greater level of inflammation, which is in turn associated with increased risk of type 2 diabetes and depression. Further research is needed to determine the direction of causation and to replicate our finding, given the cross-sectional design and the proxy use of waist-to-hip ratio for visceral adiposity.Funding
Novo Nordisk UK Research Foundation. 相似文献12.
Background
Infections can trigger acute vascular events but the differential effect of specific respiratory pathogens is unknown. We aimed to quantify the association between laboratory-confirmed respiratory bacterial or viral infections and first myocardial infarction or stroke to inform intervention development and targeting.Methods
Scottish Morbidity Record data on first myocardial infarction or stroke (International Classification of Diseases, 10th revision, codes) were linked to records of Streptococcus pneumoniae, influenza, rhinovirus, parainfluenza, respiratory syncytial virus, or human metapneumovirus from the Electronic Communication of Surveillance in Scotland (National Services Scotland) dataset on individuals aged 40 years or older from Jan 1, 2004, to Dec 31, 2014. We analysed incidence ratios for myocardial infarction or stroke in the 28 days after infection compared with baseline using self-controlled case series.Findings
There were 1227 individuals with myocardial infarction (751 men [61%]) and 762 with stroke (392 men [51%]). Median age was 68 years (IQR 59–77). The relative incidence of myocardial infarction was markedly raised in the first 1–3 days after both bacterial and viral infections (incidence ratio 5·98, 95% CI 2·47–14·4 [p<0·0001] and 5·59, 1·77–17·6 [p=0·003], respectively) and persisted for about 1 week. For stroke, the respective relative incidence after respiratory infection was even higher for days 1–3 (12·3, 5·48–27·7 [p<0·0001] and 6·79, 1·67–27·50 [p=0·007]). Elevated stroke risks after both bacterial and viral infections persisted to 28 days (p<0·0001).Interpretation
Our findings suggest that respiratory bacterial and viral infections act as vascular triggers. For stroke, the incidence ratio remained elevated a month after the date of respiratory sampling but for myocardial infarction the raised incidence ratio appeared to be more transient, suggesting potentially different mechanisms. This study highlights the need to ensure adequate uptake of influenza and pneumococcal vaccines as well as appropriate treatment during infections to reduce vascular risk.Funding
Academy of Medical Sciences. 相似文献13.
Background
Ischaemia reperfusion injury is a key cause of mortality and graft loss after liver transplantation. After tissue injury, monocytes are rapidly mobilised and recruited to injured tissue by monocyte chemoattractant protein-1 (MCP-1). Elevated MCP-1 concentrations correlate with poorer outcomes in patients after haemorrhagic stroke but have not been evaluated as a prognostic marker in clinical liver transplantation. We aimed to assess the role of inflammatory monocytes and MCP-1 in ischaemia reperfusion injuryMethods
Adult patients undergoing liver transplantation at the Royal Free Hospital, London, UK, were recruited. Liver biopsy samples were collected preimplantation and 2 h after reperfusion from five patients. Intrahepatic mononuclear cells were extracted for immediate analysis by flow cytometery. Plasma MCP-1 concentrations from 33 patients were measured preoperatively by ELISA, 2 h and 24 h after reperfusion, and correlated with graft function by measurement of day 3 aspartate aminotransferase (AST) and early allograft dysfunction (EAD) score.Findings
Flow cytometric analysis demonstrated an increase in mean classical monocytes after reperfusion compared with preimplantation (4·18% of total live cells [SD 2·61] vs 0·61 [0·38], p=0·018). In three of the five recipients we distinguished cells of donor versus recipient origin by HLA-A allele expression to demonstrate that 88% (6·24) of the classical monocytes were recipient derived in the postreperfusion biopsy sample. Median MCP-1 concentrations were significantly raised after reperfusion (385·61 pg/mL [IQR 244·75–715·20] vs 71·2 [55·61–113·99], p<0·0001) and had reduced to 740·61 (38·46–133·71) within 24 h. Patients with EAD (n=17) had significantly higher MCP-1 concentrations at 24 h than those without EAD (74·82 [66·69–219·93] vs 47·44 [29·53–77·73], p=0·037). MCP-1 concentrations at 24 h correlated with day 3 AST concentrations (p=0·002).Interpretation
Our results show that classical monocytes are rapidly recruited to the liver after ischaemia reperfusion injury, and that high MCP-1 concentrations at 24 h are associated with poorer graft function. Therefore, MCP-1 blockade presents an attractive strategy to reduce graft ischaemia reperfusion injury.Funding
None. 相似文献14.
Ester Coutinho David Menassa Leslie Jacobson Steven West Joana Domingos Teresa Moloney Marianne G Pedersen Michael E Benros Bethan Lang David Bennett Paul J Harrison Preben B Mortensen Bent Nørgaard-Pedersen David Bannerman Angela Vincent 《Lancet》2017
Background
CNS disorders can be caused by IgG antibodies to neuronal surface proteins, and these antibodies have the potential to cross the placenta. Since some of them target proteins involved in neurodevelopment, such as contactin-associated protein-2 (CASPR2), we hypothesised that they could alter developing neuronal circuits in utero and lead to neurodevelopmental disorders in the children.Methods
A dual approach to the study was undertaken. First, we studied pregnancy serum samples from two population-based Danish cohorts: a cohort of women with postpartum psychosis and a cohort of mothers of children with mental retardation and other disorders of psychological development (MR–DPD), each with individually matched controls. We screened them for the presence of antibodies to CASPR2. Then, we assessed the effects of in-utero exposure to the antibodies in a mouse maternal-to-fetal model.Findings
The combined results from these two cohorts showed that maternal antibodies to CASPR2 were associated with an increased risk of MR–DPD in the children: eight (4·4%) of 182 mothers of MR–DPD children had CASPR2 antibodies compared with only three (0·9%) of 347 mothers of children without this diagnosis (p=0·01). This association was explored by injection of mouse dams with IgG purified from CASPR2-antibody-positive patients, or from healthy controls. The mouse offspring had long-term behavioural sequelae, manifested as deficits in social interaction and social activities, and increased repetitive, non-social behaviours. When they were culled at 12 months, their brains showed abnormal migration of cortical projection neurons, increased microglial activation, and reduction in the number of glutamatergic synapses, confirming that there had been long-term changes in neurodevelopment.Interpretation
CASPR2 was identified as a specific target for maternal antibodies that can alter brain development in utero, resulting in long-term behavioural deficits and permanent abnormalities at the cellular and synaptic level. These results should encourage further epidemiological and experimental studies to confirm and explore further how CASPR2 and other maternal antibodies can lead to neurodevelopmental disorders in children.Funding
EC was funded by the Programme for Advanced Medical Education at the Calouste Gulbenkian Foundation. This work was also supported by the Stanley Medical Research Institute. Resources were provided by the Nuffield Department of Clinical Neurosciences. 相似文献15.
Background
Ethnic minorities have greatly increased rates of schizophrenia. The risk is most pronounced when individuals are living in areas with few people of the same ethnicity as them. Amygdala hyperactivity has been linked to paranoid symptoms in psychosis, and increased levels of paranoia have been observed in ethnic minority individuals. White individuals show an increased amygdala response when viewing black faces; however, whether a similar effect is seen in black individuals is not clear.Methods
20 individuals of white British ethnicity, and 20 of black ethnicity underwent a 3T MRI scan while viewing faces of black and white ethnicity. Participants were aged 18–45 years, with no history of mental illness. Population density, indices of multiple deprivation, and percentage own-group ethnic density were obtained from the 2011 census. Neighbourhood segregation was quantified with the Index of Dissimilarity method. Ethics approval was granted by the West London National Research Ethics Service Committee.Findings
At the within-group level, both groups individually showed greater right amygdala activation to the out-group faces (white ethnicity t=2·08, p=0·02; black ethnicity t=2·38, p=0·015). Between groups, the black ethnicity group showed a greater increase in right amygdala activation for the white faces compared with baseline than did the white ethnicity group (t=1·84, p=0·038). Within the black ethnicity group, amygdala reactivity to white faces showed significant correlations with measures of neighbourhood population density (r=0·61, p=0·01), segregation (r=0·71, p=0·003), deprivation (r=0·67, p=0·04), and own-group ethnic density (r=–0·51, p=0·04).Interpretation
We have shown for the first time, to our knowledge, increased amygdala response to white faces in individuals of black ethnicity. Significant correlations were observed between amygdala response and neighbourhood variables associated with increased psychosis risk. This finding has relevance for our understanding of the increased rates of paranoia and psychotic disorders in ethnic minority individuals. Further research in patient populations will help clarify aetiological relevance.Funding
National Institute for Health Research, Medical Research Council, Wellcome Trust. 相似文献16.
17.
Background
Greater investment in primary care yields better population health outcomes. However, in the past decade general practice (GP) funding has reduced, while general practitioner workload has risen and secondary care funding has increased. To date, the impact of broader aspects of GP funding has not been examined. Using newly released GP financial data, we aimed to explore the association between greater investment in primary care and secondary care usage and costs applied at a national level in England.Methods
We constructed linear regression models to explore the association between practice funding for essential services and quality and outcomes framework (QOF) achievement, secondary care usage (accident and emergency [A&E] attendance, emergency admission, and outpatient attendance rates per 1000 registered patients), and patient satisfaction, adjusted for practice and demographic variables. We then conducted financial modelling to predict the impact of a hypothetical 10% funding increase on secondary care costs, for which we used standard cost estimates.Findings
We analysed 7767 practices in England. Mean funding per patient was £79·81 (95% CI 67·01–100·67). Funding was lower in General Medical Services (GMS) practices, which hold national contracts, than in Personal Medical Services practices, which have local contracts (£76·00 [66·52–89·20] vs 84·43 [66·68–107·09]). In GMS practices, greater funding was significantly associated with lower emergency admissions (regression coefficient β=–0·22), lower A&E attendances (?1·04), and higher patient satisfaction (overall satisfaction 0·4). We found no significant association with outpatient attendance or QOF performance. In our financial model, a 10% increase in primary care funding would create a return on investment of 78% in GMS practices overall and up to 110% in GMS practices receiving funding above the national capitation formula.Interpretation
GMS practices with higher levels of funding had lower secondary care usage and higher patient satisfaction. The lack of association between funding and QOF achievement might be attributable to the different funding stream and incentives for QOF. Our findings support the case for greater investment in primary care where the value of investment is over and above the national capitation formula.Funding
National Institute for Health Research. 相似文献18.
Background
Current methods for assessing concussion during rugby matches rely on rudimentary behavioural assessment, focusing on balance and gross motor function. Cognitive testing with the Sports Concussion Assessment Tool has recently been included, but there are a paucity of normative and baseline data for this test. This study examined the utility of the Trail Making Test (TMT), which is a neuropsychological test of executive function in two parts (TMT-A and TMT-B), to assist identification of cognitive impairments caused by impacts during rugby games.Methods
27 elite male rugby league players contracted to a professional rugby club were recruited towards the end of the season. Each player was tested on three occasions within a 2 week period with both TMT-A and TMT-B for baseline assessment. Each player was additionally assessed after full contact training on 2 consecutive days and during preseason training. Individual baseline data were calculated from the best of the baseline assessments, and time differences were examined with ANOVA.Findings
No instances of concussion occurred during data collection. For TMT-A there was no significant difference (F(3, 24)=2·88, I2=0·27) between baseline (mean 13·79 s [SD 5·32], 95% CI 9·34–18·23), post-training day 1 (11·38 [2·63], 9·18–13·58), post-training day 2 (11·16 [1·94], 9·55–12·79), and preseason (11·79 [2·64], 9·58–13·99). For TMT-B there was no significant difference between baseline (31·50 [5·37], 27·01–35·99), post-training day 1 (28·07 [8·82], 20·70–35·44), post-training day 2 (26·18 [6·16], 21·03–31·33), and preseason (26·98 [4·89], 22·89–31·07).Interpretation
These findings indicate that there were no significant differences in performance of these executive tasks from baseline to post-training (end of season and preseason). These data show stability of TMT-A and TMT-B data across a competitive rugby league season. Importantly, use of measures of variation such as CIs for these tasks can provide a metric for calculating minimally important clinical differences within cognition.Funding
None. 相似文献19.
Kenneth Chan Riyaz Patel Xiangyuan Pu Iain A Simpson Robin N Poston Salim Hayek Shu Ye Arshed Quyyumi 《Lancet》2017
Background
Genome-wide association studies have identified ADAMTS7 as a risk locus for coronary artery disease and myocardial infarction. Functional studies suggest that ADAMTS7 might promote cellular processes in atherosclerosis. We sought to examine whether carriers of a loss-of-function genetic variant exhibit favourable characteristics on plaque histology, angiographic coronary artery disease severity, and cardiovascular outcomes.Methods
The single-nucleotide polymorphism rs3825807 was used as a marker for ADAMTS7. Human coronary atherosclerotic plaques (n=50) were genotyped, and characterised with immunohistochemical analysis. Burden of angiographic coronary artery disease was assessed by angiographic severity scores in two independent population-based cohorts—the Southampton Atherosclerosis Study (SAS, n=1359) in the UK, and the prospective Emory Genebank study (Emory GB, n=2684) in the USA. Follow-up data were collected in Emory GB over a median of 7 years.Findings
Human coronary atherosclerotic plaques with the loss-of-function G allele exhibited thinner fibrous cap (p=0·017) and lower percentage area of α-actin (smooth muscle cell marker) in the intima (p=0·029). After adjustment for age and sex, the G allele was associated with less coronary artery disease in both SAS (odds ratio 0·82, 95% CI 0·67–0·99), and Emory GB (0·84, 0·74–0·95). Angiographic burden was further characterised with the Gensini Score (GS) and Sullivan Extent Score (SES). ADAMTS genotypes were associated with all of the angiographic severity scores in both SAS (GS p=0·026, SES p=0·029) and Emory GB (GS p<0·0001, SES p<0·0001). Outcome analysis showed lower incidence of revascularisation for G allele carriers (hazard ratio 0·77, 95% CI 0·60–0·98), but not all cause mortality (1·12, 0·92–1·35).Interpretation
Carriers of the ADAMTS7 loss-of-function allele G had reduced atherosclerotic plaque progression, as demonstrated by thinner cap and smooth muscle migration. In addition there was less severe angiographic coronary artery disease in the SAS and Emory GB cohorts, as well as lower incidence of revascularisation procedure, further supporting the role of this protease in promoting atherosclerosis.Funding
None. 相似文献20.