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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala mark Dixon Timothy J England Kailash Krishnan Grant mair Keith W muir John Potter Christopher I Price marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena joan.a m wardlaw Nikola Sprigg Philip m Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or mann-Whitney difference(mWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(mWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Low-power SiPm readout BETA ASIC for space applications

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Nuclear Science and Techniques 2024年第3期35卷 153-169页

作者： Anand Sanmukh Sergio Gómez Albert Comerma joan mauricio Rafel manera Andreu Sanuy Daniel Guberman Roger Catala Albert Espinya marina Orta Oscar de la Torre David Gascon Departament de Física Quàntica i Astrofísica(FQA) Institut de Ciències del Cosmos(ICCUB)Universitat de Barcelona(UB)08028 BarcelonaSpain Institut d’Estudis Espacials de Catalunya(IEEC) 08034 BarcelonaSpain Electronics Department Serra Hunter fellow at Polytechnic University of Catalonia(UPC)08019 BarcelonaSpain

The BETA application-specific integrated circuit(ASIC)is a fully programmable chip designed to amplify,shape and digitize the signal of up to 64 Silicon photomultiplier(SiPm)channels,with a power consumption of approximately~1 mW/*** to its dual-path gain,the BETA chip is capable of resolving single photoelectrons(phes)with a signal-to-noise ratio(SNR)>5 while simultaneously achieving a dynamic range of~4000 ***,BETA can provide a cost-effective solution for the readout of SiPms in space missions and other applications with a maximum rate below 10 *** this study,we describe the key characteristics of the BETA ASIC and present an evaluation of the performance of its 16-channel version,which is implemented using 130 nm *** ASIC also contains two discriminators that can provide trigger signals with a time jitter down to 400 ps FWHm for 10 *** linearity error of the charge gain measurement was less than 2%for a dynamic range as large as 15 bits.

关键词： Radiation detectors Silicon photomultipliers Photon sensors Front-end electronics mixed-mode ASICs Space technology

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measures of intracranial compartments in acute intracerebral haemorrhage:data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial(RIGHT-2)

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Stroke & Vascular Neurology 2023年第2期8卷 151-160页

作者： Kailash Krishnan Zhe Kang Law Lisa J Woodhouse Rob A Dineen Nikola Sprigg joan.a m wardlaw Philip m Bath Stroke Department of Acute MedicineNottingham University Hospitals NHS TrustNottinghamUK Stroke Trials Unit University of NottinghamNottinghamUK Department of medicine National University of Malaysia Faculty of MedicineKuala LumpurMalaysia Radiological Sciences Research Group University of NottinghamNottinghamUK National Institute of Health Research Nottingham Biomedical Research Centre University of NottinghamNottinghamUK Centre for Clinical Brain Sciences UK Dementia Research InstituteChancellor's BuildingUniversity of EdinburghEdinburghUK

Background and purpose Intracerebral haemorrhage volume(ICHV)is prognostically important but does not account for intracranial volume(ICV)and cerebral parenchymal volume(CPV).We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional *** also assessed if cistern effacement,midline shift,old infarcts,leukoaraiosis and brain atrophy were associated with *** Data from 133 participants from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial trial were *** included ICHV(using ABC/2)and ICV(XYZ/2)(by independent observers);ICHV,ICV and CPV(semiautomated segmentation,SAS);atrophy(intercaudate distance,ICD,Sylvian fissure ratio,SFR);midline shift;leukoaraiosis and cistern effacement(visual assessment).The effects of these measures on death at day 4 and poor functional outcome at day 90(modified Rankin scale,mRS of>3)was *** ICV was significantly different between XYZ and SAS:mean(SD)of 1357(219)vs 1420(196),mean difference(mD)62 mL(pment for ICV measured by SAS,CPV,ICD,SFR,leukoaraiosis and cistern score(all interclass correlations,n=10:interobserver 0.72-0.99,intraobserver 0.73-1.00).ICHV/ICV and ICHV/CPV were significantly associated with mRS at day 90,death at day 4 and acute neurological deterioration(all pmilar to *** shift and cistern effacement at baseline were associated with poor functional outcome but old infarcts,leukoaraiosis and brain atrophy were *** Intracranial compartment measures and visual estimates are *** adjusted for ICH and CPV could be useful to prognosticate in acute *** presence of midline shift and cistern effacement may predict outcome but the mechanisms need validation in larger studies.

关键词： measures Tri nitrate

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Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease:baseline data and statistical analysis plan for the Lacunar Intervention Trial-2(LACI-2)(ISRCTN14911850)

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Stroke & Vascular Neurology 2023年第2期8卷 134-143页

作者： Philip m Bath Iris mhlanga Lisa J Woodhouse Fergus Doubal Katherine Oatey Alan A montgomery joan.a m wardlaw LACI-Trial Investigators Stroke Trials Unit University of NottinghamNottinghamUK Centre for Clinical Brain Sciences UK Dementia Research Institute CentreUniversity of EdinburghEdinburghUK Edinburgh Clinical Trials Unit University of EdinburghEdinburghUK Nottingham Clinical Trials Unit University of NottinghamNottinghamUK

Background Cerebral small vessel disease(SVD)causes lacunar strokes(25%of all ischaemic strokes),physical frailty and cognitive impairment and vascular and mixed *** is no specific treatment to prevent progression of *** The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD *** aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol,isosorbide mononitrate,both or neither,in addition to guideline secondary ischaemic stroke prevention,in a partial factorial *** primary outcome is feasibility of recruitment and adherence to medication;key secondary outcomes include:drug tolerability;recurrent vascular events,cognition and function at 1 year after randomisation;and safety(bleeding,falls,death).Data are number(%)and median(IQR).Results The trial commenced on 5 February 2018 and ceased recruitment on 31 may 2021 with 363 patients randomised,with the following baseline characteristics:average age 64(56.0,72.0)years,female 112(30.9%),stroke onset to randomisation 79.0(27.0,244.0)days,hypertension 267(73.6%),median blood pressures 143.0(130.0,157.0)/83.0(75.0,90.0)mm Hg,current smokers 67(18.5%),educationally achieved end of school examinations(A-level)or higher 118(32.5%),modified Rankin scale 1.0(0.0,1.0),National Institutes Health stroke scale 1.0(1.4),montreal Cognitive Assessment 26.0(23.0,28.0)and total SVD score on brain imaging 1.0(0.0,2.0).This publication summarises the baseline data and presents the statistical analysis *** The trial is currently in follow-up which will complete on 31 may 2022 with results expected in October *** registration number ISRCTN14911850.

关键词： nitrate initiated prevention

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Update on cerebral small vessel disease: a dynamic whole-brain disease

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Stroke & Vascular Neurology 2016年第3期1卷 83-92页

作者： Yulu Shi joan.a m wardlaw Centre for Clinical Brain Sciences University of EdinburghEdinburghUK Department of Neurology Zhongnan HospitalWuhan UniversityWuhanChina

Cerebral small vessel disease(CSVD)is a very common neurological disease in older *** causes stroke and dementia,mood disturbance and gait *** it is difficult to visualise CSVD pathologies in vivo,the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities,lacunar ischaemic stroke,lacunes,microbleeds,visible perivascular spaces and many haemorrhagic ***,variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies.A standardised use of terms should be encouraged in CSVD *** CSVD features have long been regarded as different lesions,but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore,owing to its diffuse nature,CSVD should be regarded as a‘whole-brain disease’.Single antiplatelet(for acute lacunar ischaemic stroke)and management of traditional risk factors still remain the most important therapeutic and preventive approach,due to limited understanding of pathophysiology in *** evidence suggests that new studies should consider drugs that target endothelium and blood–brain barrier to prevent and treat *** of CSVD might differ in Asian compared with Western populations(where most results and guidelines about CSVD and stroke originate),but more community-based data and clear stratification of stroke types are required to address this.

关键词： diagnosis drugs cerebral

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Contemporary nutrition 5th ed.

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2003年

作者： wardlaw, Gordon m

Includes bibliographical references and index.

ISBN: (纸本)007286530X

Includes bibliographical references and index.

关键词： Nutrition.

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Perspectives in nutrition 6th ed. 6th ed.

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2004年

作者： wardlaw Gordon m.

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Nurses’ and midwives’ participation and utilization of health-related research in Kenya: Implications for evidence-based practice

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International Journal of Nursing Sciences 2023年第2期10卷 199-205页

作者： Daniel m.Nzengya Albanus K.mutisya miriam C.A.Wagoro molly Secor-Turner joan Edwards Research and Innovation St.Paul’s UniversityLimuruKenya School of Nursing Jomo Kenyatta University of Agriculture&TechnologyNairobiKenya Department of Nursing Sciences University of NairobiNairobiKenya mark and Robyn Jones College of Nursing Montana State UniversityBozemanMTUSA Nelda C.Stark College of Nursing Texas Woman's UniversityHoustonTXUSA

Objective To assess the level of participation of nurses and midwives in health-related research,determine the status of utilization of research to inform nursing and midwifery practice in Kenya,and explore perspectives of nurses and midwives about strategies to empower nurses/midwives to engage in health research in *** Data were extracted from online survey responses of 156 nurse and midwife educators,practitioners,and managers/*** version 26 was used to analyze quantitative data;qualitative data were analyzed using Excel to organize data into *** Over one-third of participants reported ever publishing research(37.2%,58/156).Participants reported using knowledge gained in nursing school to guide practice most frequently(n=148).Utilization of research findings to guide practice was reported by 80.3%(110/137)of *** to enhance participation in the research included research training,research forums,policy reforms,and emphasis on research in *** There is need to intensify and prioritize proposed strategies to empower nurses/midwives to engage in health research.

关键词： Evidence-based practice Kenya midwifery Nurses Research

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Clinical management of cerebral small vessel disease:a call for a holistic approach

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Chinese medical Journal 2021年第2期134卷 127-142页

作者： Una Clancy Jason P.Appleton Carmen Arteaga Fergus N.Doubal Philip m.Bath joan.a m.wardlaw Centre for Clinical Brain Sciences and UK Dementia Research InstituteUniversity of EdinburghChancellor's Building49 Little France CrescentEdinburghEH164SPUK Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottingham NG51PBUK Stroke University Hospitals Birmingham NHS Foundation TrustMindelsohn WayEdgbastonBirmingham B152GWUK Stroke Nottingham University Hospitals NHS TrustNottingham NG51PBUK.

Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric *** brain damage,seen as focal white and deep grey matter lesions on brain magnetic resonance imaging(mRI)or computed tomography(CT),typically accumulates"covertly"and may reach an advanced state before being detected incidentally on brain scanning or causing *** have typically presented to different clinical services or been recruited into research focused on one clinical manifestation,perhaps explaining a lack of awareness,until recently,of the full range and complexity of *** this review,we discuss the varied clinical presentations,established and emerging risk factors,relationship to SVD features on mRI or CT,and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle *** core message is that effective assessment and clinical management of patients with SVD,as well as future advances in diagnosis,care,and treatment,will require a more"joined-up"’*** approach should integrate clinical expertise in stroke neurology,cognitive,and physical *** requires more clinical trials in order to improve pharmacological interventions,lifestyle and dietary modifications.A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel *** essential prerequisite to accelerating clinical trials is to improve the consistency,and standardization of clinical,cognitive and neuroimaging endpoints.

关键词： Dementia magnetic resonance imaging mild cognitive impairment Risk factors Small vessel disease Stroke Symptoms Treatment

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Diffusion-free valve for preprogrammed immunoassay with capillary microfluidics

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microsystems & Nanoengineering 2023年第4期9卷 197-209页

作者： Pooya Azizian Jasmina Casals-Terré Jordi Ricart joan m.Cabot Energy and Engineering Department Leitat Technological CenterTerrassaBarcelonaSpain mechanical Engineering Department Technical University of CataloniaTerrassaBarcelonaSpain

By manipulating the geometry and surface chemistry of microfluidic channels,capillary-driven microfluidics can move and stop fluids spontaneously without external ***,complex microfluidic circuits can be preprogrammed by synchronizing the capillary pressures and encoding the surface tensions of microfluidic chips.A key component of these systems is the capillary ***,the main concern for these valves is the presence of unwanted diffusion during the valve loading and activation steps that can cause *** this study,we design and validate a novel diffusion-free capillary valve:theπ-*** valve consists of a 3D structure and a void *** void acts as a spacer between two fluids to avoid direct *** the valve is triggered,the air trapped within the void is displaced by pneumatic suction induced from the capillary flow downstream without introducing a gas bubble into the *** proposed design eliminates diffusive mixing before valve *** simulation is used to study the function and optimize the dimensions of theπ-valve,and 3D printing is used to fabricate either the mould or the microfluidic chip.A comparison with a conventional valve(based on a constrictionexpansion valve)demonstrates that theπ-valve eliminates possible backflow into the valve and reduces the mixing and diffusion during the loading and trigger *** a proof-of-concept,this valve is successfully implemented in a capillary-driven circuit for the determination of benzodiazepine,achieving the successive release of 3 solutions in a 3Dprinted microfluidic chip without external *** results show a 40%increase in the fluorescence intensity using theπ-valve relative to the conventional ***,theπ-valve prevents cross-contamination,minimizes sample use,and facilitates a sophisticated preprogrammed release of fluids,offering a promising tool for conducting automated immunoassays applicable at point-of-

关键词： capillary steps eliminate

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