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Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

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General Psychiatry 2024年第1期37卷 103-111页

作者： Viktor H Ahlqvist Christina Dardani Paul Madley-Dowd Harriet forbes jessica Rast Caichen Zhong Renee M Gardner Christina Dalman Kristen Lyal cRAIG Newschaffer Torbjorn Tomson Michael Lundberg Daniel Berglind Neil M Davies Brian K Lee Cecilia Magnusson Dheeraj Rai Department of Global Public Health Karolinska InstitutetStockholmSweden Medical Research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK Centre for Academic Mental Health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical MedicineLondonUK A.j.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of Health and Human Development Pennsylvania State UniversityState CollegePAUSA Department of Clinical Neuroscience Karolinska InstitutetStockholmSweden Centre for Epidemiology and Community Medicine Region StockholmStockholmSweden K.G jebsen Center for Genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK NIHR Biomedical Research Centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

Background Psychiatric comorbidities are common in patients with *** for the co-occurrence of psychiatric conditions and epilepsy remain poorly *** We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these *** Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with *** then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score ***,we assessed the potential bidirectional relationships using two-sample Mendelian *** In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric *** example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric *** Psychiatric comorbidities are common in patients with *** correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric *** findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psy

关键词： epilepsy Psychiat lifetime

An in situ monitoring campaign of a hard rock pillar at great depth within a Canadian mine

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journal of Rock Mechanics and Geotechnical Engineering 2020年第3期12卷 427-448页

作者： Bradley forbes Nicholas Vlachopoulos Mark S.Diederichs Andrew j.Hyett Allan Punkkinen Department of Geological Sciences and Geological Engineering Queen’s UniversityKingstonOntarioK7L 3N6Canada Department of Civil Engineering Royal Military College of CanadaKingstonOntarioK7K 7B4Canada YieldPoint Inc. KingstonOntarioK7M 4W9Canada Normet Canada Ltd. LivelyOntarioP3Y 0B3Canada

A recent research campaign at a Canadian nickel-copper mine involved instrumenting a hard rock sill drift pillar with an array of multi-point rod extensometers,distributed optical fibre strain sensors,and borehole pressure cells(BHPCs).The instrumentation spanned across a 15.24 m lengthwise segment of the relatively massive granitic pillar situated at a depth of 2.44 km within the *** May 2016 and March 2017,the pillar’s displacement and pressure response were measured and correlated with mining activities on the same level as the pillar,including:(1)mine-by of the pillar,(2)footwall drift development,and(3)ore body stoping *** displacements of the pillar,the extensometers provided high temporal resolution(logged hourly)and the optical fibre strain sensors provide high spatial resolution(measured every 0.65 mm along the length of each sensor).The combination of sensing techniques allowed centimetre-scale rock mass bulking near the pillar sidewalls to be distinguished from microstrain-scale fracturing towards the core of the ***,the influence and extent of a mine-scale schistose shear zone transecting the pillar was *** converting measured rock mass displacement to velocity,a process was demonstrated which allowed mining activities inducing displacements to be categorised by time-duration and cumulative *** over half of the analysed mining activities,displacements were determined to prolong for over an hour,predominately resulting in submillimetre cumulative displacements,but in some cases multi-centimetre cumulative displacements were *** time-dependent behaviour was more pronounced within the vicinity of the plumb shear *** measurements were also used to assess selected support member load and elongation mobilisation per mining *** was found that a combined static load and elongation capacity of reinforcing members was essential to maintaining excavation stability,while

关键词： Hard rock pillar Rockburst Rock mass bulking Distributed optical fibre strain sensing Extensometer In situ monitoring High stress Dynamic support

Disruption of Dhcr7 and Insig1/2 in cholesterol metabolism causes defects in bone formation and homeostasis through primary cilium formation

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Bone Research 2020年第1期8卷 39-52页

作者： Akiko Suzuki Kenichi Ogata Hiroki Yoshioka junbo Shim Christopher AWassif forbes DPorter junichi Iwata Department of Diagnostic&Biomedical Sciences The University of Texas Health Science Center at HoustonSchool of DentistryHoustonTXUSA Center for Craniofacial Research The University of Texas Health Science Center at HoustonSchool of DentistryHoustonTXUSA Division of Translational Medicine Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentBethesdaMDUSA Pediatric Research Center The University of Texas Health Science Center at HoustonMcGovern Medical SchoolHoustonTXUSA MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Human linkage studies suggest that craniofacial deformities result from either genetic mutations related to cholesterol metabolism or high-cholesterol maternal diets. However, little is known about the precise roles of intracellular cholesterol metabolism in the development of craniofacial bones, the majority of which are formed through intramembranous ossification. Here, we show that an altered cholesterol metabolic status results in abnormal osteogenesis through dysregulation of primary cilium formation during bone formation. We found that cholesterol metabolic aberrations, induced through disruption of either Dhcr7(which encodes an enzyme involved in cholesterol synthesis) or Insig1 and Insig2(which provide a negative feedback mechanism for cholesterol biosynthesis), result in osteoblast differentiation abnormalities. Notably, the primary cilia responsible for sensing extracellular cues were altered in number and length through dysregulated ciliary vesicle fusion in Dhcr7 and Insig1/2 mutant osteoblasts. As a consequence, WNT/β-catenin and hedgehog signaling activities were altered through dysregulated primary cilium ***, the normalization of defective cholesterol metabolism by simvastatin, a drug used in the treatment of cholesterol metabolic aberrations, rescued the abnormalities in both ciliogenesis and osteogenesis in vitro and in vivo. Thus, our results indicate that proper intracellular cholesterol status is crucial for primary cilium formation during skull formation and homeostasis.

关键词： metabolism cholesterol homeostasis

Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

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World journal of Gastroenterology 2016年第35期22卷 8026-8040页

作者： Christopher Leung Chandana B Herath Zhiyuan jia Sof Andrikopoulos Bronwyn E Brown Michael j Davies Leni R Rivera john B Furness josephine M forbes Peter W Angus Department of Medicine the University of MelbourneAustin HealthHeidelbergMelbourne Victoria 3084Australia Department of Gastroenterology and Hepatology Austin HealthAustin HospitalHeidelberg MelbourneVictoria 3084 Australia Heart Research Institute Newtown New South Wales 2042Austrulia University of Melbourne Victoria 3052Australia Metabolic Research Unit School of MedicineDeakin UniversityVictoria 3216Austrialia Glycation and Diabetes Complications Group Mater Medical Research InstituteSouth BrisbaneQueensland 4101Australia

AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.

关键词： Advanced glycation end-products Fructose Steatohepatitis Non-alcoholic fatty liver disease Hepatic fibrosis Oxidative stress

Shrinking multiplexed orbital angular momentum to the nanoscale

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Light(Science & Applications) 2021年第11期10卷 2026-2027页

作者： Chao He Yijie Shen Andrew forbes Martin j.Booth Department of Engineering Science University of OxfordParks RoadOxford OX13PJUK Optoelectronics Research Centre University of SouthamptonSouthampton SO171BJUK Department of Engineering Science University of OxfordParks RoadOxfordOX13PJUK

Orbital angular momentum interactions at the nanoscale have remained elusive because the phase structure becomes *** researchers have shown how to overcome this with tightly focused beams,demonstrating a recordhigh si... 详细信息

关键词： momentum nanoscale overcome

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压燃式发动机增压空气的冷却(下)

国外铁道机车与动车 1965年第12期 19-24页

作者： M.K.forbes R.j.Hampson 付正偉

六、凝汽现象如果冷却表面的温度低于增压空气的露点时,增压空气中的水蒸汽就会凝结在壁面上。在任何一个装置的冷却器中,开始冷凝的具体条件取决于涡轮增压器吸入空气的相对湿度、增压器的增压比、冷却壁面的温度,而冷却壁面的温度主... 详细信息

六、凝汽现象如果冷却表面的温度低于增压空气的露点时,增压空气中的水蒸汽就会凝结在壁面上。在任何一个装置的冷却器中,开始冷凝的具体条件取决于涡轮增压器吸入空气的相对湿度、增压器的增压比、冷却壁面的温度,而冷却壁面的温度主要取决于冷却水温度。图23所示曲线为在涡轮增压式发动机上可能碰到的各种状况

关键词：发动机功率空气压力捐失大气压力增压器工业气体空气冷却装置冷却器

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羊毛地毯纱定捻技术——研发的基础

国际纺织导报 2014年第3期42卷 27-,40页

作者： E.A.forbes j.-H.Dittrich 卢兰兰林肯大学 Leibniz大学

纳米技术的最新进展和行业现行的环保要求,再次掀起了羊毛地毯纱定捻方面技术创新的热潮.测量纱线定捻效果是这一发展的基石,但纱线扭转参数(如纱线扭矩)尚没有标准的测量方法,这便为其他一些相对实用的方法提供了机会.Wronz定捻测试仪(... 详细信息

纳米技术的最新进展和行业现行的环保要求,再次掀起了羊毛地毯纱定捻方面技术创新的热潮.测量纱线定捻效果是这一发展的基石,但纱线扭转参数(如纱线扭矩)尚没有标准的测量方法,这便为其他一些相对实用的方法提供了机会.Wronz定捻测试仪(Wronz Set Tester,简称WST)便是其中之一,它对独创的Chemset技术的发展具有重要作用,可令羊毛地毯的加工过程平稳,纱线质量明显提高.Mckinnon关于研发基础(包括WST推进创新的论述)正被弱化的观点,以及羊毛研究界偶尔一些常规知识的丢失,对今后的成功发展不会产生特别大的影响.

关键词：定捻地毯纱

作物和土壤中拟除虫菊酯农药残留的简便分析方法

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世界农药 1987年第1期 54-56页

作者： Staut forbes Alan j.Dutton 陆贻通 Shell公司Sittingbourne研究中心 Shell公司Sittingbourne研究中心

测定作物和土壤中各种合成拟除虫菊酯残留量的分析方法,文献已有报道。类似的方法也可用于测定作物和土壤中的氯氰菊酯(Shell公司注册商标为‘Ripcord’)和WL-

关键词：氯氰菊醋除虫菊宿根花卉啤酒花忽布分析方法作物农药残留

英国全科诊所提供规模化医疗服务状况的观察性研究

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中国全科医学 2019年第36期22卷 4464-4464页

作者：本刊编辑部 forbes L j forbes H SUTTON M

背景在过去5年中,英国出台政策鼓励全科诊所联合其他诊所为超过30000人的人群(“规模化医疗服务”)提供全科诊疗服务。目的调查提供规模化医疗服务的英国全科诊所数量及其服务人群状况。设计与场所本项观察性研究于英国的全科诊所中开... 详细信息

背景在过去5年中,英国出台政策鼓励全科诊所联合其他诊所为超过30000人的人群(“规模化医疗服务”)提供全科诊疗服务。目的调查提供规模化医疗服务的英国全科诊所数量及其服务人群状况。设计与场所本项观察性研究于英国的全科诊所中开展。方法资料来源于英国国家医疗服务体系发表的以团队形式执业的全科诊所的自我报告数据以及不同组织和执业团队网站上的报告。将全科诊所执业状况按服务规模分类。对各类服务规模的全科诊所服务人群的年龄分布、社会经济剥夺程度、来自地区乡村化状况以及慢性病患病率进行分析。结果约55%的英国全科诊所(服务人数共计为335000000例)以单独执业或者联合执业形式为超过30000人的人群提供规模化医疗服务。约5%的全科医疗机构,包括大型诊所、超级合伙人和多点执业组织,以密切协作的组织模式提供核心诊疗服务。约50%的全科诊所以松散的协作形式合作,提供非核心诊疗服务,例如在晚上和周末提供服务。但是本研究中关于组织模式和合作目的之间关系的相关数据非常有限。结论在2018年初,为了提供规模化医疗服务,大约5%的全科诊所密切合作,约50%的全科诊所以松散的协作形式合作。但是本研究纳入的数据有限。未来应纳入更多临床数据以评估规模化诊疗服务对患者疗效的影响。

关键词：观察性研究医疗服务服务人群全科医疗诊疗服务报告数据乡村化临床数据