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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 Joanna 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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Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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Journal of sport and Health science 2024年第5期13卷 611-620页

作者： Benjamin T.schumacher michael J.Lamonte Andrea Z.LaCroix Eleanor m.simonsick steven P.Hooker Humberto Parada Jr. john Bellettiere Arun Kumar Herbert Wertheim school of Public Health and Human Longevity science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and Biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of California san Diego moores Cancer Center La JollaCA 92093USA Computer science and Engineering and Halicioglu Data science Institute University of California San DiegoLa JollaCA 92093USA

Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(mL),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several mL VO_(2max)prediction ***:The Baltimore Longitudinal study of Aging(BLsA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(sVm)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall BLsA,(b)by sex,(c)using all BLsA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:The age was 69.0±10.4 years(mean±sD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:measured VO_(2max)is a strong predictor of *** mL can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms Epidemiology mortality

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superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime s.Rosa Duque samuel m.s.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng mu Yuet Chung Tsun ming Lau manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang sara Chaothai Tsz Chun Kwan john K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos m.T.Lee Jennifer H.Y.Lam sau man Chan Wilfred H.s.Wong Issan Y.s.Tam masashi mori sophie A.Valkenburg malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent medicine The University of Hong KongHong KongChina school of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(Im)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(sARs-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over Im administration in *** Participants aged 11–17 years received two doses of Im or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(Im-CC versus ID-CC)and post-dose 3(ImCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** spike protein(s)immunoglobulin G(IgG),s-receptor-binding domain(RBD)IgG,s IgG Fcγreceptor IIIa(FcγRIIIa)-binding,sNm[sum of individual(s),nucleocapsid protein(N),and membrane protein(m)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),sNm-specific IL-2^(+)CD8^(+),s-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and m-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to Im-CC,whereas IgG avidity was *** ID-CCC,s-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,s IgG avidity,s IgG FcγRIIIa-binding,m-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for Im-CC,ID-CC,Im-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and m-specific T-cell responses by ID inactivated sARsCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

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Enhancing Pneumonia Detection in Pediatric Chest X-Rays Using CGAN-Augmented Datasets and Lightweight Deep Transfer Learning models

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Journal of Data Analysis and Information Processing 2024年第1期12卷 1-23页

作者： Coulibaly mohamed Ronald Waweru mwangi john m. Kihoro Department of mathematics Pan African University Institute for Basic Sciences Technology and Innovation (PAUSTI) Nairobi Kenya Department of Computing Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya school of Computing and mathematics The Cooperative University of Kenya Nairobi Kenya

Pneumonia ranks as a leading cause of mortality, particularly in children aged five and under. Detecting this disease typically requires radiologists to examine chest X-rays and report their findings to physicians, a task susceptible to human error. The application of Deep Transfer Learning (DTL) for the identification of pneumonia through chest X-rays is hindered by a shortage of available images, which has led to less than optimal DTL performance and issues with overfitting. Overfitting is characterized by a model’s learning that is too closely fitted to the training data, reducing its effectiveness on unseen data. The problem of overfitting is especially prevalent in medical image processing due to the high costs and extensive time required for image annotation, as well as the challenge of collecting substantial datasets that also respect patient privacy concerning infectious diseases such as pneumonia. To mitigate these challenges, this paper introduces the use of conditional generative adversarial networks (CGAN) to enrich the pneumonia dataset with 2690 synthesized X-ray images of the minority class, aiming to even out the dataset distribution for improved diagnostic performance. subsequently, we applied four modified lightweight deep transfer learning models such as Xception, mobileNetV2, mobileNet, and EfficientNetB0. These models have been fine-tuned and evaluated, demonstrating remarkable detection accuracies of 99.26%, 98.23%, 97.06%, and 94.55%, respectively, across fifty epochs. The experimental results validate that the models we have proposed achieve high detection accuracy rates, with the best model reaching up to 99.26% effectiveness, outperforming other models in the diagnosis of pneumonia from X-ray images.

关键词： Pneumonia Detection Pediatric Radiology CGAN (Conditional Generative Adversarial Networks) Deep Transfer Learning medical Image Analysis

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Geochemistry and mineralogy of beach sediments in the northern Gulf of mexico,Tamaulipas state,mexico:implication for provenance

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Journal of Palaeogeography 2024年第3期13卷 375-400页

作者： mayank shukla sanjeet K.Verma mayla A.Ramos-Vázquez john s.a.m.trong-a.trin Karla R.Hernández-martínez sumit mishra Vivek P.malviya Héctor Hernández-mendoza Posgrado de la Division de Geociencias Aplicadas Instituto Potosino de Investigacion Científica y Tecnologica(IPICYT)Camino a la Presa San José2055San Luis Potosí78216Mexico Division de Geociencias Aplicadas Instituto Potosino de Investigación Científica y Tecnologica(IPICYT)Camino a la Presa San Jose 2055San Luis Potosí78216Mexico Universidad Nacional Autonoma de méxico Instituto de Ciencias del Mar y LimnologíaUnidad de ProcesosOceanicos y CosterosCiudad UniversitariaCiudad de México 04510Mexico Department of marine sciences Bharathidasan UniversityTiruchirappalli620024Tamil NaduIndia Instituto de Geociencias Universidad Nacional Autonoma de MéxicoBoulevard Juriquilla 300176230JuriquillaQueretaroMexico Department of Applied Geology Dr.Harisingh Gour Central UniversitySagar470002Madhya PradeshIndia Instituto de Investigacion de Zonas Desérticas Universidad Autònoma de San Luis PotosíAltair 200CP 78377San LuisS.L.P.Mexico Universidad del Centro de mexico Capitán Caldera 75CP 78250San LuisS.L.P.Mexico

Geochemical and mineralogical studies were performed in the La Pesca(LP)and Tesoro Altamira(TA)beach sediments,located in the Tamaulipas state,northern Gulf of *** main aim of this study is to infer the weathering history and provenance and to discriminate the tectonic environment of the beach *** sediments are composed of quartz with small amounts of accessory minerals such as plagioclase,calcite,orthoclase,microcline,and *** beach sediments are classified as fine-grained and very well sorted,however LP has coarse skewed and leptokurtic sediments,whereas TA has fine-skewed and very leptokurtic *** chemical index of weathering(CIW’)indicates intense weathering in the source *** quartz grain microtextures in the LP and TA are classified into mechanical,chemical,and mechanical/chemical *** features such as fractures,pits,percussion marks,abrasion fatigue,and V-shaped marks favor high-energy littoral,fluvial,subaqueous-marine,and aeolian *** chemical features indicate solution pits and crystalline overgrowth,which suggests a silica saturated marine *** mechanical/chemical features display adhering particles and elongated depressions suggest formation in a sub-aqueous nearshore marine *** and trace elements-based provenance discrimination diagrams indicate a felsic source derived from the mesa Central(mC),sierra madre Oriental(smOr)and Oaxaquia *** major and trace element concentrations imply a passive margin setting for the northern Gulf of mexico,which is consistent with the general geology.

关键词： Beach sediments Geochemistry mineralogy Provenance Tamaulipas Tectonic setting

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The first record of a Konservat-Lagerstätten in which early post-settlement stages of fossil archaeobalanids(Cirripedia:Balanomorpha)are preserved

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Integrative Zoology 2024年第2期19卷 200-223页

作者： Tomáš KOCÍ Rok GAŠPARIC john BUCKERIDGE martina KOCOVÁ VEsELsKÁ Aleš ŠOsTER Ivancická581 PragueCzech Republic Palaeontological Department Natural History MuseumNational MuseumPragueCzech Republic Oertijdmuseum Bosscheweg 80Boxtel5293 WBThe Netherlands Institute for Palaeobiology and Evolution Novi TrgKamnikSlovenia Earth and Oceanic systems Group RMIT UniversityMelbourneAustralia museums Victoria CarltonVictoriaAustralia Department of Paleobiology and Paleoecology Institute of Geology of the Czech Academy of SciencesPragueCzech Republic Institute of Geology and Palaeontology Charles UniversityPragueCzech Republic Faculty of Natural sciences and Engineering University of LjubljanaLjubljanaSlovenia

A diverse sessile barnacle fauna from a miocene shallow-water deposit at Dolnja stara vas in slovenia is *** includes the first descriptions of early post settlement juveniles of Actinobalanus sloveniensis attached to mangrove *** represent three distinct growth phases,the earliest being interpreted as being less than 24 h post settlement,the others being 1 to 2 days post *** assessment of their taphonomy is *** adult balanomorphs are attached to a variety of organic substrates,including mangrove leaves and branches,fragments of the conifers?Taxodioxylon,Carapoxylon,pine cones,molluscs,and cetacean *** barnacles include ***,Amphibalanus venustus,and Perforatus perforatus—many with opercula retained within the *** retains some of the original shell *** is the second record of barnacle–plant associations from the Central Paratethys from Kamnik and *** paleoecology and paleogeography of the site are discussed.

关键词： acorn barnacles barnacle metamorphosis epibiont paleoecology taxonomy

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Optimization of stealthwatch Network security system for the Detection and mitigation of Distributed Denial of service (DDos) Attack: Application to smart Grid system

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Communications and Network 2024年第3期16卷 108-134页

作者： Emmanuel s. Kolawole Penrose s. Cofie john H. Fuller Cajetan m. Akujuobi Emmanuel A. Dada Justin F. Foreman Pamela H. Obiomon Electrical and Computer Engineering Department Prairie View A&M University Prairie View TX USA

The smart Grid is an enhancement of the traditional grid system and employs new technologies and sophisticated communication techniques for electrical power transmission and distribution. The smart Grid’s communication network shares information about status of its several integrated IEDs (Intelligent Electronic Devices). However, the IEDs connected throughout the smart Grid, open opportunities for attackers to interfere with the communications and utilities resources or take clients’ private data. This development has introduced new cyber-security challenges for the smart Grid and is a very concerning issue because of emerging cyber-threats and security incidents that have occurred recently all over the world. The purpose of this research is to detect and mitigate Distributed Denial of service [DDos] with application to the Electrical smart Grid system by deploying an optimized stealthwatch secure Network analytics tool. In this paper, the DDos attack in the smart Grid communication networks was modeled using stealthwatch tool. The simulated network consisted of secure Network Analytic tools virtual machines (Vms), electrical Grid network communication topology, attackers and Target Vms. Finally, the experiments and simulations were performed, and the research results showed that stealthwatch analytic tool is very effective in detecting and mitigating DDos attacks in the smart Grid system without causing any blackout or shutdown of any internal systems as compared to other tools such as GNs3, Nessi2, NIssT Framework, OmNeT++, INET Framework, ReasE, Ns2, Ns3, m5 simulator, OPNET, PLC & TIA Portal management software which do not have the capability to do so. Also, using stealthwatch tool to create a security baseline for smart Grid environment, contributes to risk mitigation and sound security hygiene.

关键词： smart Grid system Distributed Denial of service (DDos) Attack Intrusion Detection and Prevention systems Detection mitigation and stealthwatch

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Damage evolution of rock-encased-backfill structure under stepwise cyclic triaxial loading

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Journal of Rock mechanics and Geotechnical Engineering 2024年第2期16卷 597-615页

作者： Xin Yu Yuye Tan Weidong song john Kemeny shengwen Qi Bowen Zheng songfeng Guo Key Laboratory of shale Gas and Geoengineering Institute of Geology and GeophysicsChinese Academy of SciencesBeijing100089China Innovation Academy for Earth science Chinese Academy of SciencesBeijing100089China University of Chinese Academy of sciences Beijing100049China school of Civil and Resources Engineering University of Science and Technology BeijingBeijing100083China Key Laboratory of High-Efficient mining and safety of metal mines(ministry of Education of China) University of Science and Technology BeijingBeijing100083China Department of mining and Geological Engineering University of ArizonaTucsonAZ86721USA

Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping *** understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 mPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3D fracture *** results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill *** important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases ***,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction *** finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture *** transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 mPa *** the findings have important practical implications on t

关键词： Rock and backfill Triaxial cyclic loading Volume fraction Damage evolution 3D visualization

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What diameter?What height?Influence of measures of average tree size on area-based allometric volume relationships

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Forest Ecosystems 2024年第1期11卷 100-109页

作者： Yilin Wang john A.Kershaw mark J.Ducey Yuan sun James B.mcCarter Integrated Forest mensuration and systems Analysis Laboratory Faculty of Forestry and Environmental ManagementUniversity of New BrunswickFrederictonNBCanada Department of Natural Resources and the Environment University of New HampshireDurhamNHUSA College of Forestry Nanjing Forestry UniversityNanjing210037China scientific Programmer RayonierYuleeFLUSA

Volume is an important attribute used in many forest management *** from 83 fixed-area plots located in central New Brunswick,Canada,are used to examine how different measures of stand-level diameter and height influence volume prediction using a stand-level variant of Honer's(1967)volume *** density was included in the models(Volume=f(Diameter,Height,Density))choice of diameter measure was more important than choice of height *** density was not included(Volume=f(Diameter,Height)),the opposite was *** models with density included,moment-based estimators of stand diameter and height performed better than all other *** models without density,largest tree estimators of stand diameter and height performed better than other *** overall best equation used quadratic mean diameter,Lorey's height,and density(root mean square error=5.26 m^3·ha^(-1);1.9%relative error).The best equation without density used mean diameter of the largest trees needed to calculate a stand density index of 400 and the mean height of the tallest 400 trees per ha(root mean square error=32.08 m^(3)·ha^(-1);11.8%relative error).The results of this study have some important implications for height subsampling and LiDAR-derived forest inventory analyses.

关键词： Allometric relationships stand structure Volume estimation stand-level attributes

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Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

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Neural Regeneration Research 2024年第7期19卷 1437-1445页

作者： steinunn sara Helgudóttir Anne skøttrup mørkholt Jacek Lichota Preben Bruun-Nyzell mads Christian Andersen Nanna marie Juhl Kristensen Amanda Krøger Johansen mikela Reinholdt Zinn Hulda maria Jensdóttir john Dirk Vestergaard Nieland 2N Pharma Aps NOVI Science ParkAalborgDenmark molecular Pharmacology Group Department of Health Science and TechnologyAalborg UniversityAalborgDenmark

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s *** the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these *** considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological *** innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers *** this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative *** provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ***,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter ***,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

关键词： brain disease carnitine palmitoyl transferase 1 epigenetics metabolism gut microbiome mitochondrial dysfunction neurodegeneration oxidative stress

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