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Development,validation and comparison of multivariable risk scores for prediction of total stroke and stroke types in Chinese adults:a prospective study of 0.5 million adults

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Stroke & Vascular Neurology 2022年第4期7卷 328-336,I0023-I0045页

作者： Matthew Chun robert clarke Tingting Zhu David Clifton Derrick A Bennett Yiping Chen Yu Guo Pei Pei Jun Lv Canqing Yu Ling Yang Liming Li Zhengming Chen Benjamin J Cairns 无 Clinical Trial Service Unit and Epidemiological Studies Nuffield Department of Population HealthUniversity of OxfordOxfordUK Department of Engineering Science University of OxfordOxfordUK Department of Biomedical Engineering Oxford-Suzhou Centre for Advanced ResearchSuzhouChina Medical Research Council Health Research Unit Nuffield Department of Population HealthUniversity of OxfordOxfordUK CKB Project Department Fuwai Hospital Chinese Academy of Medical SciencesNational Center for Cardiovascular DiseasesBeijingChina CKB Project Department Chinese Academy of Medical SciencesBeijingChina Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina Department of Epidemiology Peking University Center for Public Health and Epidemic Preparedness and ResponseBeijingChina On behalf of the China Kadoorie Biobank Collaborative Group

Background and purpose Low-income and middle-income countries have the greatest stroke burden,yet remain *** study compared the utility of Framingham versus novel risk scores for prediction of total stroke and stroke types in Chinese *** China Kadoorie Biobank(CKB)is a prospective study of 512726 adults,aged 30-79 years,recruited from 10 areas in China in *** 1 January 2018,43234 incident first stroke cases(36310 ischaemic stroke(IS);8865 haemorrhagic stroke(HS))were recorded in 503842 participants with no history of stroke at *** compared the predictive utility of the Framingham Stroke Risk Profile(FSRP)with novel CKB stroke risk scores and included recalibration,refitting,stratifying by study area and addition of other risk *** was assessed using area under the receiver operating characteristic curve(AUC)and calibration was assessed using Greenwood-Nam-D’Agostinoχ^(2) *** Incidence of total stroke varied fivefold by area in *** FSRP had good discrimination for total stroke(AUC(95%CI);men:0.78(0.77 to 0.79),women:0.77(95%CI 0.76 to 0.78)),but poor calibration(χ^(2);men:1,825,women:3,053),substantially underestimating absolute *** reducedχ^(2) by>80%,but did not improve *** the FSRP did not materially improve discrimination,but further improved *** by area improved discrimination(AUC;men:0.82(0.82 to 0.83);women:0.82(0.82 to 0.83)),but not *** other risk factors yielded modest,but statistically significant,improvements in the *** findings for IS and HS were similar to those for total *** The FSRP reliably differentiated Chinese adults with incident stroke,but substantially underestimated the absolute risks of *** local risk prediction equations that took account of differences in stroke incidence within China enhanced risk prediction of total stroke and major stroke pathological type

关键词： prediction income absolute

Interferon Gamma Restores Breast Cancer Sensitivity to Fulvestrant by Regulating STAT1,IRF1,NFκB,Specific BCL2 Family Members,and Signaling to Caspase-dependent Apoptosis

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Interferon Gamma Restores Breast Cancer Sensitivity to Fulve...

A T follicular helper cell origin for T regulatory type 1 cells

中国病理生理学会受体、肿瘤和免疫专业委员会联合学术会议

作者： Rebecca B.Riggins robert clarke Lombardi Comprehensive Cancer Center and Department of Oncology Georgetown University School of Medicine

Antiestrogens are effective therapies for the management of estrogen receptor-alpha positive(ER+) breast ***,both de novo and acquired resistance occur and remain major problems in the clinical *** gamma(IFNγ) is an inflammatory cytokine that induces the expression and function of Interferon Regulatory Factor-1(IRF1),a tumor suppressor gene that can increase antiestrogen *** show that IFNγbut not IFNα,IFNβ,or ICI induces IRF1 expression in antiestrogen resistant MCF7/LCC9 and LY2 ***,IFNγrestores the responsiveness of these cells to Fulvestrant(ICI;ICI 182,780;Faslodex).Increased IRF1 activation suppresses NFκB p65(RELA) activity and inhibits the expression of prosurvival(BCL2,BCLW),and induces the expression of proapoptotic members(BAK,mitochondrial BAX) of the BCL2 *** molecular signaling is associated with activation of STAT1,and leads to increased mitochondrial membrane permeability,activation of CASP7,CASP8,and CASP9,and induction of apoptosis but not autophagy. While antiestrogen resistant cells are capable of inducing autophagy through IFN-mediated signaling,their ability to do so through antiestrogen-regulated signaling is *** abilities of IFNγto activate CASP8, induce apoptosis,and restore antiestrogen sensitivity,are prevented by siRNA targeting IRF1,while transient overexpression of IRF1 mimics the effects of IFNγ*** observations support the exploration of clinical trials combining antiestrogens and compounds that can induce IRF1,such as IFNγ, for the treatment of some ER-positive breast cancers.

关键词： apoptosis autophagy BCL2 breast neoplasms caspases cell death drug resistance estrogen receptor modulators Fulvestrant interferons Tamoxifen

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Cellular & Molecular Immunology 2023年第5期20卷 489-511页

作者： Patricia Solé Jun Yamanouchi Josep Garnica Muhammad Myn Uddin robert clarke Joel Moro Nahir Garabatos Shari Thiessen Mireia Ortega Santiswarup Singha Debajyoti Mondal César Fandos Julio Saez-Rodriguez Yang Yang Pau Serra Pere Santamaria Institut D'investigacions Biomediques August Pi i Sunyer BarcelonaSpain Department of Microbiology Immunology and Infectious DiseasesSnyder Institute for Chronic DiseasesCumming School of MedicineUniversity of CalgaryCalgaryABCanada Institute of Computational Biomedicine Faculty of MedicineHeidelberg University HeidelbergGermany Department of Biochemistry and Molecular Biology Cumming School of MedicineUniversity of CalgaryCalgaryABCanada.

Chronic antigenic stimulation can trigger the differentiation of antigen-experienced CD4+T cells into T regulatory type 1(TR1)cells,a subset of interleukin-10-producing Treg cells that do not express *** identities of the progenitor(s)and transcriptional regulators of this T-cell subset remain ***,we show that the peptide-major histocompatibility complex class Il(pMHCll)monospecific immunoregulatory T-cell pools that arise in vivo in different genetic backgrounds in response to pMHCll-coated nanoparticles(pMHCll-NPs)are invariably comprised of oligoclonal subpools of T follicular helper(TFH)and TR1 cells with a nearly identical clonotypic composition but different functional properties and transcription factor expression *** analyses of scRNAseq data and multidimensional mass cytometry revealed progressive downregulation and upregulation of TFH and TR1 markers,***,pMHCIl-NPs trigger cognate TR1 cell formation in TFH cell-transfused immunodeficient hosts,and T-cell-specific deletion of Bcl6 or Irf4 blunts both the TFH expansion and TR1 formation induced by *** contrast,deletion of Prdm1 selectively abrogates the TFH-to-TR1 ***6 and Prdm1 are also necessary for anti-CD3 mAbinduced TR1 ***,TFH cells can differentiate into TR1 cells in vivo,and BLIMP1 is a gatekeeper of this cellular reprogramming event.

关键词： T-regulatory type 1(TR1)cells autoimmunity T follicular helper(TFH)cells transdifferentiation nanomedicine

An Effective Procedure for the RAPD Analysis of Hemp Cannabissativa L.

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Journal of Chinese Pharmaceutical Sciences 2001年第2期10卷 67-69页

作者： SongShujuan robert.C.clarkeI ShaoHong DepartmentofBiologyandGenetics PekingUniversityHealthScienceCenterBeijing100083 InternationalHempAssociation.P.O.Box75007 I070AAAmsterdamTheNetherland

China has a great resource of Cannabis. Research on the taxonomy and morphology of Chinese Cannabis has been carried out, but so far no molecular genetic research has been published. Random amplifiedpolymorphic DNA (RAPD) is a suitable technique for molecular genetic research on Cannabis. In tills experiment,using Cannabis herbarium specimens as a source of genetic materials, the correlative conditions of the Polymerasechain reaction (PCR), (i.e., gradient density of Mg^2+, dNTPs, Taq DNA polymerase, anneal temperature, anneal timeand reaction cycles) were examined separately. An effective procedure for the RAPD analysis of Cannabis wasobtained.

关键词：大麻 RAPD 标本麻药

Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese

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Stroke & Vascular Neurology 2024年第4期9卷 399-406,I0044-I0065页

作者： Songchun Yang Zhijia Sun Dong Sun Canqing Yu Yu Guo Dianjianyi Sun Yuanjie Pang Pei Pei Ling Yang Iona Y Millwood Robin G Walters Yiping Chen Huaidong Du Yan Lu Sushila Burgess Daniel Avery robert clarke Junshi Chen Zhengming Chen Liming Li Jun Lv On behalf of the China Kadoorie Biobank Collaborative Group Department of Epidemiology&Biostatistics School of Public HealthPeking UniversityBeijingChina Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunanChina Peking University Center for Public Health and Epidemic Preparedness&Response BeijingChina Key Laboratory of Epidemiology of Major Diseases(Peking University) Ministry of EducationBeijingChina Fuwai Hospital Chinese Academy of Medical Sciences BeijingChina Medical Research Council Population Health Research Unit at the University of Oxford OxfordUK Clinical Trial Service Unit&Epidemiological Studies Unit(CTSU) Nuffield Department of Population HealthUniversity of OxfordOxfordUK NCDs Prevention and Control Department Suzhou CDCSuzhouJiangsuChina China National Center for Food Safety Risk Assessment BeijingChina State Key Laboratory of Vascular Homeostasis and Remodeling Peking UniversityBeijingChina 不详

Background and purpose Previous studies,mostly focusing on the European population,have reported polygenic risk scores(PRSs)might achieve risk stratification of *** aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese *** Participants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set(n=22191)and a population-based testing set(n=72150).Four previously developed PRSs were included,and new PRSs for stroke and its subtypes were *** PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing *** proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes(ischaemic stroke(IS),intracerebral haemorrhage(ICH)and subarachnoid haemorrhage(SAH)).Results In the testing set,during 872919 person-years of follow-up,8514 incident stroke events were *** PRSs of any stroke(AS)and IS were both positively associated with risks of AS,IS and ICH(p<0.05).The HR for per SD increment(HR_(SD))of PRSAS was 1.10(95%CI 1.07 to 1.12),1.10(95%CI 1.07 to 1.12)and 1.13(95%CI 1.07 to 1.20)for AS,IS and ICH,*** corresponding HR_(SD) of PRS_(IS) was 1.08(95%CI 1.06 to 1.11),1.08(95%CI 1.06 to 1.11)and 1.09(95%CI 1.03 to 1.15).PRS_(ICH) was positively associated with the risk of ICH(HR_(SD)=1.07,95%CI 1.01 to 1.14).PRSS_(AH) was not associated with risks of stroke and its *** addition of current PRSs offered little to no improvement in stroke risk prediction and risk *** In this Chinese population,the association strengths of current PRSs with risks of stroke and its subtypes were moderate,suggesting a limited value for improving risk prediction over traditional risk factors in the context of current genome-wide association study under-representing the East Asia

关键词： testing prediction increment

中国非动脉硬化性心血管疾病人群脂蛋白(a)水平分布特征及影响因素

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中华流行病学杂志 2024年第6期45卷 779-786页

作者：柯雅蕾潘烺吕筠孙点剑一裴培陈怡平杨玲杜怀东 clarke robert 陈君石陈铮鸣章晓陈婷李润琴齐丽彤李立明余灿清中国慢性病前瞻性研究项目协作组北京大学公共卫生学院流行病与卫生统计学系北京100191 北京大学公众健康与重大疫情防控战略研究中心北京100191 重大疾病流行病学教育部重点实验室(北京大学) 北京100191 牛津大学临床与流行病学研究中心纳菲尔德人群健康系牛津OX37LF 国家食品安全风险评估中心北京100022 北京诺华制药有限公司北京102200 北京大学第一医院心内科北京100034 不详

目的描述中国非动脉硬化性心血管疾病(ASCVD)人群脂蛋白(a)[Lp(a)]的分布并分析其影响因素。方法基于中国慢性病前瞻性研究项目的一项巢式病例对照研究,选取其中进行了血液生化指标检测的对照人群进行分析,使用参比实验室检定的多克隆... 详细信息

目的描述中国非动脉硬化性心血管疾病(ASCVD)人群脂蛋白(a)[Lp(a)]的分布并分析其影响因素。方法基于中国慢性病前瞻性研究项目的一项巢式病例对照研究,选取其中进行了血液生化指标检测的对照人群进行分析,使用参比实验室检定的多克隆抗体比浊法测定Lp(a)水平,≥75.0 nmol/L定义为高Lp(a)。采用多因素logistic回归模型分析Lp(a)水平的影响因素。结果在纳入研究的5870名非ASCVD人群中,Lp(a)水平呈正偏态分布,M(Q_(1),Q_(3))为17.5(8.8,43.5)nmol/L。多因素logistic回归分析结果显示,女性与高Lp(a)相关(OR=1.23,95%CI:1.05~1.43),中心性肥胖者的高Lp(a)风险降低(OR=0.68,95%CI:0.52~0.89)。随TC、LDL-C、载脂蛋白A1(Apo A1)和载脂蛋白B(Apo B)水平升高,高Lp(a)风险增加,各升高组的OR值(95%CI)分别为2.40(1.76~3.24)、2.68(1.36~4.93)、1.29(1.03~1.61)和1.65(1.27~2.13);HDL-C降低组高Lp(a)风险降低,OR值(95%CI)为0.76(0.61~0.94);而TG、Apo A1与Apo B的比值(Apo A1/B)与高Lp(a)风险呈负相关,TG升高组的OR值(95%CI)为0.73(0.60~0.89),Apo A1/B升高组的OR值(95%CI)为0.60(0.50~0.72);Lp(a)水平与血脂指标(除Apo A1外)的相关性均存在线性趋势(线性趋势检验P≤0.001)。未发现行为生活方式因素如饮食、吸烟、体力活动水平与Lp(a)水平存在统计学关联。结论Lp(a)水平与性别及中心性肥胖有关,但受行为生活方式因素影响较小。

关键词：脂蛋白(a) 非动脉硬化性心血管疾病人群分布影响因素

Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores:evidence from the China Kadoorie Biobank

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Chinese Medical Journal 2023年第20期136卷 2476-2483页

作者： Songchun Yang Dong Sun Zhijia Sun Canqing Yu Yu Guo Jiahui Si Dianjianyi Sun Yuanjie Pang Pei Pei Ling Yang Iona YMillwood Robin GWalters Yiping Chen Huaidong Du Zengchang Pang Dan Schmidt Rebecca Stevens robert clarke Junshi Chen Zhengming Chen Jun Lv Liming Li On Behalf of the China Kadoorie Biobank Collaborative Group Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Peking University Center for Public Health and Epidemic Preparedness&Response Beijing 100191China Fuwai Hospital Chinese Academy of Medical Sciences Beijing 100730China Medical Research Council Population Health Research Unit at the University of Oxford Oxford OX37LFUK Clinical Trial Service Unit and Epidemiological Studies Unit(CTSU) Nuffield Department of Population HealthUniversity of OxfordOxford OX37LFUK Qingdao Center of Disease Control and Prevention QingdaoShandong 266033China China National Center for Food Safety Risk Assessment Beijing 100738China 不详

Background:Several studies have reported that polygenic risk scores(PRSs)can enhance risk prediction of coronary artery disease(CAD)in European ***,research on this topic is far from sufficient in non-European countries,including *** aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese ***:Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training(n=28,490)and testing sets(n=72,150).Ten previously developed PRSs were evaluated,and new ones were developed using clumping and thresholding or LDpred *** PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing *** risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide *** of the 10-year first CAD events was assessed using hazard ratios(HRs)and measures of model discrimination,calibration,and net reclassification improvement(NRI).Hard CAD(nonfatal I21-I23 and fatal I20-I25)and soft CAD(all fatal or nonfatal I20-I25)were analyzed ***:In the testing set,1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 *** HR per standard deviation of the optimal PRS was 1.26(95%CI:1.19-1.33)for hard *** on a traditional CAD risk prediction model containing only non-laboratory-based information,the addition of PRS for hard CAD increased Harrell’s C index by 0.001(-0.001 to 0.003)in women and 0.003(0.001 to 0.005)in *** the different high-risk thresholds ranging from 1%to 10%,the highest categorical NRI was 3.2%(95%CI:0.4-6.0%)at a high-risk threshold of 10.0%in *** association of the PRS with soft CAD was much weaker than with hard CAD,leading to minimal or no improvement in the soft CAD ***:In this Chinese population sam

关键词： Coronary artery disease Polygenic risk score Risk prediction model Chinese population

Field testing innovative differential geospatial and photogrammetric monitoring technologiesin mountainous terrain near Ashcroft,British Columbia,Canada

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Journal of Mountain Science 2021年第1期18卷 1-20页

作者： David HUNTLEY Peter BOBROWSKY Roger MACLEOD robert COCKING Jamel JOSEPH Drew ROTHERAM-clarke Geological Survey of Canada 1500-605 Robson StreetVancouverBritish ColumbiaV6B 5J3Canada Geological Survey of Canada 9860 West Saanich RoadSidneyBritish ColumbiaV8L 4B2Canada

This paper presents a novel approach to continuously monitor very slow-moving translational landslides in mountainous terrain using conventional and experimental differential global navigation satellite system(d-GNSS)technologies.A key research question addressed is whether displacement trends captured by a radio-frequency“mobile”d-GNSS network compare with the spatial and temporal patterns in activity indicated by satellite interferometric synthetic aperture radar(InSAR)and unmanned aerial vehicle(UAV)*** testing undertaken at Ripley Landslide,near Ashcroft in south-central British Columbia,Canada,demonstrates the applicability of new geospatial technologies to monitoring ground control points(GCPs)and railway infrastructure on a landslide with small and slow annual displacements(<10 cm/yr).Each technique records increased landslide activity and ground displacement in late winter and early *** this interval,river and groundwater levels are at their lowest levels,while ground saturation rapidly increases in response to the thawing of surficial earth materials,and the infiltration of snowmelt and runoff occurs by way of deep-penetrating tension cracks at the head scarp and across the main slide *** over the last decade provides vital information for government agencies,national railway companies,and other stakeholders to understand geohazard risk,predict landslide movement,improve the safety,security,and resilience of Canada’s transportation infrastructure;and reduce risks to the economy,environment,natural resources,and public safety.

关键词： Landslide Change detection monitoring Global Navigation Satellite System Real-Time Kinematic System GeocubeTM Bathymetric Survey Unmanned Aerial Vehicle Interferometric Synthetic Aperture Radar

The Internet of Things and Next-generation Public Health Information Systems

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Communications and Network 2013年第3期5卷 4-9页

作者： robert Steele Andrew clarke Discipline of Health Informatics the University of Sydney Sydney Australia

The Internet of things has particularly novel implications in the area of public health. This is due to (1) The rapid and widespread adoption of powerful contemporary Smartphone’s;(2) The increasing availability and use of health and fitness sensors, wearable sensor patches, smart watches, wireless-enabled digital tattoos and ambient sensors;and (3) The nature of public health to implicitly involve connectivity with and the acquisition of data in relation to large numbers of individuals up to population scale. Of particular relevance in relation to the Internet of Things (IoT) and public health is the need for privacy and anonymity of users. It should be noted that IoT capabilities are not inconsistent with maintaining privacy, due to the focus of public health on aggregate data not individual data and broad public health interventions. In addition, public health information systems utilizing IoT capabilities can be constructed to specifically ensure privacy, security and anonymity, as has been developed and evaluated in this work. In this paper we describe the particular characteristics of the IoT that can play a role in enabling emerging public health capabilities;we describe a privacy-preserving IoT-based public health information system architecture;and provide a privacy evaluation.

关键词： Internet of Things Public Health Population Health Privacy Anonymity