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

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 epilepsy.Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy.We 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 regression.Finally,we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results 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 conditions.For 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 conditions.Conclusions Psychiatric comorbidities are common in patients with epilepsy.Genetic correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions.These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.

关键词： epilepsy Psychiat lifetime

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Thermochemical splitting of CO_(2) on perovskites for CO production: A review

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Journal of Energy Chemistry 2024年第3期90卷 464-485,I0011页

作者： Biduan Chen harriet Kildahl Hui Yang Yulong Ding Lige Tong Li Wang School of Energy and Environmental Engineering University of Science and Technology BeijingBeijing 100083China School of Chemical Engineering University of BirminghamBirmingham B152TTUnited Kingdom Beijing Engineering Research Centre of Energy Saving and Environmental Protection Beijing 100083China

Energy supply dominated by fossil energy has been and remains the main cause of carbon dioxide emissions,the major greenhouse gas leading to the current grave climate change challenges.Many technical pathways have been proposed to address the challenges.Carbon capture and utilization(CCU) represents one of the approaches and thermochemical CO_(2) splitting driven by thermal energy is a subset of the CCU,which converts the captured CO_(2) into CO and makes it possible to achieve closed-loop carbon recirculation.Redox-active catalysts are among the most critical components of the thermochemical splitting cycles and perovskites are regarded as the most promising catalysts.Here we review the latest advancements in thermochemical cycles based on perovskites,covering thermodynamic principles,material modifications,reaction kinetics,oxygen pressure control,circular strategies,and demonstrations to provide a comprehensive overview of the topical area.Thermochemical cycles based on such materials require the consideration of trade-off between cost and efficiency,which is related to actual material used,operation mode,oxygen removal,and heat recovery.Lots of efforts have been made towards improving reaction rates,conversion efficiency and cycling stability,materials related research has been lacking-a key aspect affecting the performance across all above aspects.Double perovskites and composite perovskites arise recently as a potentially promising addition to material candidates.For such materials,more effective oxygen removal would be needed to enhance the overall efficiency,for which thermochemical or electrochemical oxygen pumps could contribute to efficient oxygen removal as well as serve as means for inert gas regeneration.The integration of thermochemical CO_(2) splitting process with downstream fuel production and other processes could reduce costs and increase efficiency of the technology.This represents one of the directions for the future research.

关键词： Perovskite Thermochemical cycles CO_(2) splitting Fuel production Non-stoichiometric

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A One Health approach to fight antimicrobial resistance in Uganda: Implementation experience, results, and lessons learned

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Biosafety and Health 2024年第2期6卷 125-132页

作者： Reuben Kiggundu J.P.Waswa Niranjan Konduri Hassan Kasuja Marion Murungi Patrick Vudriko harriet Akello Eric Lugada Cecilia Muiva Esther Were Dinah Tjipura Henry Kajumbula Kate Kikule Emmanuel Nfor Mohan P.Joshi USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthKampala 256Uganda USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthArlingtonVA 22203USA College of Veterinary Medicine Animal Resources and BiosecurityMakerere UniversityKampala 256Uganda Ministry of Health Uganda Kampala 256Uganda USAID Strengthening Supply Chain Systems Activity Management Sciences for HealthKampala 256Uganda USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthNairobi 254Kenya Department of Microbiology College of Health SciencesMakerere UniversityKampala 256Uganda

Uganda has been implementing the Global Health Security Agenda(GHSA)since 2015 to build its capacity according to World Health Organization(WHO)Benchmarks on International Health Regulations Capacities.The country remains prone to outbreaks,with more than 2o disease outbreaks reported in the past five years,including Ebola virus disease,Crimean-Congo haemorrhagic fever,Marburg haemorrhagic fever,measles,yel-low fever,coronavirus disease 2019(COVID-19),and cholera.Antimicrobial resistance(AMR)is an ongoing challenge.Uganda scored capacity level 3 on infection prevention and control(IPC)and antimicrobial steward-ship(AMS)in the 2017 Joint External Evaluation(JEE)assessment.Identified gaps were being addressed after a self-assessment in 2021.This paper describes the technical assistance approaches provided to Uganda by the Medicines,Technologies,and Pharmaceutical Services Program,funded by the United States(U.S.)Agency for International Development,and implemented by Management Sciences for Health.The program,through a One Health approach,supported systematic capacity strengthening based on the JEE's capacity advancement framework for global health security,specifically relating to AMR.The program's interventions impacted 32 WHO benchmark actions(7 for AMR multisectoral coordination,16 for IPC,and 9 for AMS),contributing to Uganda's strengthened GHSA capacity.Leveraging success built on the AMR platform,the program trained 745 health workers in IPC for the Ebola virus and provided support for simulation exercises by eight district IPC teams.The program also worked with the Ministry of Health to coordinate IPC for the COVID-19 response in five health regions,covering 45 districts and reaching 5,452 health workers at 858 health facilities.2024 Chinese Medical Association Publishing House.Published by Elsevier BV.

关键词： One health Antimicrobial resistance Antibiotic resistance Jointexternal evaluation Global health security Uganda Africa WHO Benchmarks for International Health Regulations Capacities

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Thermochemical splitting of carbon dioxide by lanthanum manganites-understanding the mechanistic effects of doping

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Energy Storage and Saving 2022年第4期1卷 309-324页

作者： harriet Kildahl Hui Cao Yulong Ding School of Chemical Engineering University of BirminghamB152TTUnited Kingdom

This review investigates the effect of different dopants on the oxygen evolution and carbon dioxide splitting abilities of the lanthanum manganites.Particular focus was placed on the lanthanide,alkaline earth metals,redox-active transition metal,and non-redox active Group 3 metals.The review suggests that a small ionic radius lanthanide on the A-site can increase the size discrepancy,leading to Mn-O_(6) octahedra tilting and more facile Mn-O bond breaking.Doping the A-site with a divalent alkaline earth element can increase the valance of the transition metal,leading to greater reduction capabilities.A transition metal with one electron in the e_(g) orbital is the most effective for reduction while for oxidation,zero electrons in the high-energy e_(g) orbitals is optimal.Finally,doping of the B-site with metals such as gallium or aluminium aids in sintering resistance and allows reactivity to remain constant over multiple cycles.Higher reduction temperatures and moderate re-oxidation temperatures also promote higher fuel yields as does the active reduction of the perovskite under hydrogen,although the total energy consumption implications of this are unknown.Far more is known about the mechanism of the reduction reaction than the oxidation reaction,therefore more research in this area is required.

关键词： CO_(2)splitting Thermochemical cycle Perovskite Energy conversion Doping

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Detection of alcoholic liver disease

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World Journal of Gastroenterology 2001年第3期7卷 297-302页

作者： harriet Gordon Consultant Physician and Gastroenterologist The Royal Hampshire County HospitalWinchesterHampshireUK

INTRODUCTIONAlcohol has been used in society over centuries and all over the world for its mood-lifting properties and taste. It is probably ,however ,the commonest drug of abuse world-wide and unfortunately causes considerable morbidity, mortality and social disruption .In 1990 the cost tl the USA was more than $ 100 billion and 100 000 lives.The relationship between alcohol and mankind is well documented from the earliest tines .

关键词： liver diseases, alcoholic/diagnosis biological markers

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Strongyloidiasis in Ethiopia:systematic review on risk factors,diagnosis,prevalence and clinical outcomes

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Infectious Diseases of Poverty 2019年第3期8卷 32-42页

作者： Yitagele Terefe Kirstin Ross harriet Whiley College of Veterinary Medicine Haramaya UniversityP.O.Box 138Dire DawaEthiopia Foodborne Pathogen Diagnosis Research Laboratory Haramaya UniversityP.O.Box 138Dire DawaEthiopia Environmental Health College of Science and EngineeringFlinders UniversityGPO Box 2100AdelaideSouth Australia 5001Australia

Background:Strongyloidiasis is a gastrointestinal infection caused by the parasitic nematode Strongyloides stercorolis.It is estimated to infea up to 370 million people globally and is predominately found in tropical and subtropical areas of socioeconomic disadvantage.Main body:This systematic literature review identified studies published in the last ten years on the risk factors,diagnosis,prevalence and/or clinical outcomes of strongyloidiasis in Ethiopia.The prevalence of 5.stercoralis ranged from 0.2 to 11.1%in adults,0.3%to 20.7%in children,1.5%to 17.3%in HIV positive adults and 5%in HIV positive children.The identified studies primarily used microscopy based techniques that potentially underestimated the prevalence four fold compared with serology and PCR.Strongyloidiasis in children presents a particularly significant issue in Ethiopia as children often presented with anemia,which is associated with impaired mental and cognitive development.The most significant risk factor for strongyloidiasis was HIV status and although other risk factors were identified for helminth infections,none were statistically significant for 5.stercoralis specifically.Several studies detected 5.stercoralis in dogs and non-biting cyclorrhaphan flies.However,future research is needed to explore the role of these reservoirs in disease transmission.Conclusions:This review demonstrated that strongyloidiasis is an overlooked and neglected disease in Ethiopia.There is a need for a systematic approach using a combination of molecular and serology based diagnostic methods to ascertain the true incidence and burden of strongyloidiasis in Ethiopia.Further research is also needed to break the cycle of transmission by identifying environmental reservoirs,risk factors and exploring the potential for zoonotic transfer.

关键词： Neglected tropical disease Soil transmitted helminth Public health Strongyloides stercoralis AIDS HIV Anemia

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Bleeding after suction rectal biopsy with Rbi2:identification of the root cause through a multi-staged approach

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World Journal of Pediatric Surgery 2021年第4期4卷 57-59页

作者： harriet J Corbett Ramanand Jeeneea Iain Hennessey Department of Surgery Royal Liverpool Childrens NHS TrustLiverpoolUK

Introduction Suction rectal biopsy(SRB)is a key diagnostic tool in Hirschsprung’s disease.The original Noblett device has been superseded by modern alternatives including the Rbi2 rectal biopsy gun.We describe a comparison of biopsy results from the Noblett device and the Rbi2 gun and an investigation into significant post-biopsy bleeding episodes with the latter.Methods A retrospective review of SRB episodes between 2006 and 2014 was undertaken to audit biopsy success rates.Significant post-procedure bleeding after SRB with the Rbi2 gun prompted further investigations.Results Biopsies taken with the Noblett gun were more likely to be inadequate(Noblett 82/197(40%)vs Rbi277/438(18%)).After biopsy with the Rbi2 gun,2 infants suffered from significant bleeding requiring resuscitation,blood product support and multiple theater episodes.As there were no reported cases of bleeding with the Rbi2 gun,a report was made to the Medicines&Healthcare products Regulatory Agency who identified incorrect biopsy technique as a potential contributing factor.A questionnaire of trainees and consultants found unexpected individual variation in SRB technique,with some users applying excessive suction.Conclusions Significant bleeding occurred after SRB with the Rbi2 gun,excessive suction was thought to be the cause.

关键词： biopsy prompt likely

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Conceptualising Intangible Heritage in Urban Environments: Challenges for Implementing the HUL Recommendation

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Built Heritage 2018年第4期2卷 72-81页

作者： harriet Jane Deacon Centre for Dance Research Coventry UniversityCoventryUnited Kingdom

The Historic Urban Landscape(HUL)Recommendation(UNESCO 2011)suggests that heritage management should be holistic,integrated,people-centred and focused on sustainable development goals.Both tangible and intangible heritage should be taken into account,allowing for appropriate change over time.A variety of stakeholders should be involved in planning processes,including all levels of government,NGOs and communities.Intercultural dialogue and mediation,as well as tools such as documentation,inventorying and mapping should be used to identify multiple layers of heritage.Implementing the Recommendation thus offers a wonderful opportunity to develop consultative,bottom-up,integrated planning for sustainable development in urban areas.This paper suggests that one barrier to integrating management planning for tangible and intangible heritage is a persistent confusion about what‘intangible heritage’is and why it deserves protection.Is it the values that local communities associate with their environment(‘intangible values’),or is it cultural practices that they happen to perform in that environment(intangible cultural heritage,or ICH)?Should‘intangible heritage’be managed as an attribute attesting to the authenticity of tangible fabric,or as a subject of safeguarding in its own right?If it means all these things at the same time,why is the same concept being used for so many different ideas and what are the consequences?The paper will suggest that a clearer conceptual understanding of intangible heritage is necessary to effectively integrate it into urban management strategies under the HUL approach.

关键词： intangible heritage Historic Urban Landscape UNESCO intangible heritage convention

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Connecting brain and body:Transdiagnostic relevance of connective tissue variants to neuropsychiatric symptom expression

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World Journal of Psychiatry 2021年第10期11卷 805-820页

作者： harriet Emma Clare Sharp Hugo D Critchley Jessica A Eccles Department of Medical Neuroscience Brighton and Sussex Medical SchoolUniversity of SussexBrighton BN19PXEast SussexUnited Kingdom Department of Psychiatry Sussex Partnership NHS Foundation TrustWorthingBN133EPWest SussexUnited Kingdom

The mind is embodied;thoughts and feelings interact with states of physiological arousal and physical integrity of the body.In this context,there is mounting evidence for an association between psychiatric presentations and the expression variant connective tissue,commonly recognised as joint hypermobility.Joint hypermobility is common,frequently under-recognised,significantly impacts quality of life,and can exist in isolation or as the hallmark of hypermobility spectrum disorders(encompassing joint hypermobility syndrome and hypermobile Ehlers-Danlos syndrome).In this narrative review,we appraise the current evidence linking psychiatric disorders across the lifespan,beginning with the relatively well-established connection with anxiety,to hypermobility.We next consider emerging associations with affective illnesses,eating disorders,alongside less well researched links with personality disorders,substance misuse and psychosis.We then review related findings relevant to neurodevelopmental disorders and stress-sensitive medical conditions.With growing understanding of mind-body interactions,we discuss potential aetiopathogenetic contributions of dysautonomia,aberrant interoceptive processing,immune dysregulation and proprioceptive impairments in the context of psychosocial stressors and genetic predisposition.We examine clinical implications of these evolving findings,calling for increased awareness amongst healthcare professionals of the transdiagnostic nature of hypermobility and related disorders.A role for early screening and detection of hypermobility in those presenting with mental health and somatic symptoms is further highlighted,with a view to facilitate preventative approaches alongside longer-term holistic management strategies.Finally,suggestions are offered for directions of future scientific exploration which may be key to further delineating fundamental mind-body-brain interactions.

关键词： Joint hypermobility Hypermobile Ehlers-Danlos syndrome Psychopathology Psychiatric disorders Neurodevelopmental disorders Mind-body relations

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Nucleotide sequence conservation of novel and established cis-regulatory sites within the tyrosine hydroxylase gene promoter

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Frontiers in Biology 2015年第1期10卷 74-90页

作者： Meng WANG Kasturi BANERJEE harriet BAKER John W. CAVE Burke Medical Research Institute White Plains NY 10605 USA Weill Cornell Medical College Brain and Mind Research Institute NY 10065 USA

Tyrosine hydroxylase （TH） is the rate-limiting enzyme in catecholamine biosynthesis and its gene proximal promoter （〈 1 kb upstream from the transcription start site） is essential for regulating transcription in both the developing and adult nervous systems. Several putative regulatory elements within the TH proximal promoter have been reported, but evolutionary conservation of these dements has not been thoroughly investigated. Since many vertebrate species are used to model development, function and disorders of human catecholaminergic neurons, identifying evolutionarily conserved transcription regulatory mechanisms is a high priority. In this study, we align TH proximal promoter nucleotide sequences from several vertebrate species to identify evolutionarUy conserved motifs. This analysis identified three elements （a TATA box, cyclic AMP response element （CRE） and a 5＇-GGTGG-3＇ site） that constitute the core of an ancient vertebrate TH promoter. Focusing on only eutherian mammals, two regions of high conservation within the proximal promoter were identified： a -250 bp region adjacent to the transcription start site and a -85 bp region located approximately 350 bp further upstream. Within both regions, conservation of previously reported cis-regulatory motifs and human single nucleotide variants was evaluated. Transcription reporter assays in a TH-expressing cell line demonstrated the functionality of highly conserved motifs in the proximal promoter regions and electromobility shift assays showed that brain-region specific complexes assemble on these motifs. These studies also identified a non-canonical CRE binding （CREB） protein recognition element in the proximal promoter. Together, these studies provide a detailed analysis of evolutionary conservation within the TH promoter and identify potential cisregulatory motifs that underlie a core set of regulatory mechanisms in mammals.

关键词： catecholamine dopamine transcription evolution

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