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Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic cerebrovascular Events III (TRAcE III): a randomised, phase III, open- label, controlled trial

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Stroke & vascular Neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong bruce c v campbell Marc Fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang Neurology Beijing Tiantan HospitalBeijingChina china National clinical Research center for Neurological Diseases BeijingChina Department of Medicine and Neurology The University of MelbourneMelbourneVictoriaAustralia Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of Neurology and comprehensive Stroke center Massachusetts General HospitalBostonMassachusettsUSA Department of Neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within *** study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LvO)of anterior circulation beyond *** and design Tenecteplase Reperfusion Therapy in Acute Ischaemic cerebrovascular Events-III(TRAcE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical *** who had an ischaemic stroke due to anterior circulation LvO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volumech ratio≥1.8 and mismatch volume≥15mL)based on cT perfusion or MRI perfusion-weighted imaging(PWI)were included and randomised to rhTNK-tPA 0.25mg/kg(single bolus)to a maximum of 25mg or standard medical ***,we will exclude patients who are intended for direct *** will be followed up for 90 *** outcomes Primary efficacy outcome is modified Rankin Scale(mRS)score≤1 at 90 *** efficacy outcomes include ordinal distribution of mRS at 90 days,major neurological improvement defined by a decrease≥8 points compared with the initial deficit or a score≤1 on the National Institutes of Health Stroke Scale(NIHSS)at 72 hours,mRS score≤2 at 90 days,the rate of improvement on Tmax>6s at 24 hours and NIHSS score change from baseline at *** outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 *** TRAcE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LvO beyond *** registration number NcT05141305.

关键词： Therapy random Rational

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Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours(HOPE):protocol for a randomised,controlled,multicentre study

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Stroke & vascular Neurology 2024年第3期9卷 318-323,I0274-I0282页

作者： Zhongyu Luo Ying Zhou Yaode He Shenqiang Yan Zhicai chen Xuting Zhang Yi chen Lu-Sha Tong Wansi Zhong Haitao Hu Kemeng Zhang Jiansheng Yang bruce c v campbell Min Lou Department of Neurology Zhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina Department of Medicine and Neurology Melbourne Brain Centre at Royal Melbourne HospitalParkvilleVictoriaAustralia

Background While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke(AIS)within 4.5hours of symptom onset,there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic *** To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on cT perfusion at 4.5–24hours after stroke onset(for stroke with unknown onset time,the midpoint of the time last known to be well and symptom recognition time;for wake-up stroke,the midpoint of the time last known to be well or sleep onset and wake up time)will benefit from intravenous *** HOPE is a prospective,multicentre,randomised,open-label blinded endpoint trial with the stage of phase *** treatment allocation employs 1:1 *** treatment arm under investigation is alteplase with standard therapy,the control arm is standard *** imaging criteria include ischaemic core volume≤70mL,penumbra≥10mL and mismatch≥20%.Study outcomes The primary outcome is non-disabled functional outcome(assessed as modified Rankin Scale score of 0–1 at 90 days).Discussion HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5–24hours,which has the potential to extend time window and expand eligible population for thrombolysis therapy.

关键词： patients intravenous centre

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Endovascular thrombectomy for stroke: current best practice and future goals

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Stroke & vascular Neurology 2016年第1期1卷 16-22页

作者： bruce c v campbell Geoffrey A Donnan Peter J Mitchell Stephen M Davis Department of Medicine and Neurology Melbourne Brain Centre at the Royal Melbourne HospitalUniversity of MelbourneParkvilleVictoriaAustralia The Florey Institute of Neuroscience and Mental Health University of MelbourneParkvilleVictoriaAustralia Department of Radiology Royal Melbourne HospitalUniversity of MelbourneParkvilleVictoriaAustralia

Endovascular thrombectomy for large vessel ischaemic stroke substantially reduces disability,with recent positive randomised trials leading to guideline changes *** review discusses in detail the evidence provided by recent randomised trials and metaanalyses,the remaining areas of uncertainty and the future directions for *** data from existing trials have demonstrated the robust benefit of endovascular thrombectomy for internal carotid and proximal middle cerebral artery *** remains for more distal occlusions where the efficacy of alteplase is greater,less tissue is at risk and the safety of endovascular procedures is less *** artery occlusion was excluded from the trials,but with a dire natural history and proof of principle that rapid reperfusion is effective,it seems reasonable to continue treating these patients pending ongoing trial *** has been no evidence of heterogeneity in treatment effect in clinically defined subgroups by age,indeed,those aged>80 years have at least as great an overall reduction in disability and reduced *** there was no heterogeneity across the range of baseline stroke severities included in the *** that routine use of general anaesthesia reduces the benefit of endovascular thrombectomy is increasing and conscious sedation is generally preferred unless severe agitation or airway compromise is *** impact of time delays has become clearer with description of onset to imaging and imaging to reperfusion *** in the onset to imaging reduce the proportion of patients with salvageable brain ***,in the presence of favourable imaging,rapid treatment appears beneficial regardless of the onset to imaging time *** to reperfusion delays lead to decay in the clinical benefit achieved,particularly in those with less robust collateral *** brain imaging options to assess prognosis have various advantages and disadvan

关键词： routine epoch benefit

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Tenecteplase Reperfusion therapy in Acute ischaemic cerebrovascular Events-Ⅱ (TRAcE Ⅱ): rationale and design

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Stroke & vascular Neurology 2022年第1期7卷 71-76页

作者： Shuya Li bruce c v campbell Lee H Schwamm Marc Fisher Mark Parsons Hao Li Yuesong Pan Yongjun Wang china National clinical Research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Medicine and Neurology University of MelbourneMelbourneVictoriaAustralia Department of Neurology and comprehensive Stroke center Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of Neurology Liverpool HospitalSouth Western Sydney Clinical SchoolSydneyNew South WalesAustralia

Background and purpose Tenecteplase(TNK)is a promising agent for treatment of acute ischaemic stroke(AIS).We hypothesised that recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)is non-inferior to rt-PA in achieving excellent functional outcome at 90 days,when administered within 4.5 hours of ischaemic stroke *** and design Tenecteplase Reperfusion therapy in Acute ischemic cerebrovascular Events(TRAcE)is a phase Ⅲ,multicentre,prospective,randomised,open-label,blinded-end point non-inferiority *** eligible for intravenous thrombolysis therapy are randomised to rhTNK-tPA 0.25 mg/kg(single bolus)to a maximum of 25 mg or rt-PA 0.9 mg/kg(10%bolus+90%infusion/1 hour)to a maximum of 90 *** considered necessary for the patient’s health may be given at the discretion of the investigator during 90-day *** outcomes The primary study outcome is excellent functional outcome defined as modified Rankin Scale(mRS)0–1 at 90 *** efficacy outcomes include favourable functional outcome defined as mRS≤2 at 90 days,ordinal distribution of mRS and major neurological improvement on the National Institutes of Health Stroke *** outcomes are symptomatic intracranial haemorrhage within 36 hours and death from any *** There is no completed registration study of TNK in AIS *** Ⅱ strives to provide evidence for a new drug application for rhTNK-tPA in AIS within 4.5 hours through a well-designed and rigorously executed randomised trial in china.

关键词： infusion acute rational

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Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase Ⅱ randomised placebo-controlled double-blind multicentre trial

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Stroke & vascular Neurology 2022年第2期7卷 158-165页

作者： Nawaf Yassi Henry Zhao Leonid churilov bruce c v campbell Teddy Wu Henry Ma Andrew cheung Timothy Kleinig Helen Brown Philip choi Jiann-Shing Jeng Annemarei Ranta Hao-Kuang Wang Geoffrey c cloud Rohan Grimley Darshan Shah Neil Spratt Der-Yang cho Karim Mahawish Lauren Sanders John Worthington Ben clissold Atte Meretoja vignan Yogendrakumar Mai Duy Ton Duc Phuc Dang Nguyen Thai My Phuong Huy-Thang Nguyen chung Y Hsu Gagan Sharma Peter J Mitchell Bernard Yan Mark W Parsons christopher Levi Geoffrey A Donnan Stephen M Davis Department of Medicine and Neurology Melbourne Brain Centre at The Royal Melbourne HospitalThe University of MelbourneParkvilleVictoriaAustralia Population Health and Immunity Division Walter and Eliza Hall Institute of Medical ResearchParkvilleVictoriaAustralia Ambulance victoria MelbourneVictoriaAustralia Melbourne Medical School The University of MelbourneMelbourneVictoriaAustralia Stroke Division The Florey Institute of Neuroscience and Mental HealthParkvilleVictoriaAustralia Department of Neurology Christchurch HospitalChristchurchNew Zealand Department of Neurology Monash Medical CentreMonash UniversityClaytonVictoriaAustralia Department of Interventional Neuroradiology Liverpool HospitalLiverpoolNew South WalesAustralia Department of Neurology Royal Adelaide HospitalAdelaideSouth AustraliaAustralia Department of Neurology Princess Alexandra HospitalWoolloongabbaQueenslandAustralia Department of Neurology Box Hill HospitalEastern HealthBox HillVictoriaAustralia Stroke centre and Department of Neurology National Taiwan University HospitalTaipeiTaiwan Department of Medicine Dunedin School of MedicineUniversity of OtagoWellingtonNew Zealand Department of Neurosurgery E-Da HospitalYanchaoKaohsiungTaiwan Department of Neurology Alfred HospitalMelbourneVictoriaAustralia Department of clinical Neuroscience Monash University Central Clinical SchoolMelbourneVictoriaAustralia Department of Medicine Sunshine Coast University HospitalNambourQueenslandAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia Department of Neurology John Hunter HospitalThe University of NewcastleNewcastleNew South WalesAustralia Department of Neurosurgery China Medical University HospitalTaichungTaiwan Department of Internal Medicine Palmerston North HospitalPalmerston NorthNew Zealand Department of Neurology St Vincent's HospitalFitzroyVictoriaAustralia Department of Neurology Royal Prince Alfred HospitalCamperdownNew South WalesAustra

Rationale Haematoma growth is common early after intracerebral haemorrhage(IcH),and is a key determinant of *** acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce haematoma *** and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units(STOP-MSU)is a phase Ⅱ double-blind,randomised,placebo-controlled,multicentre,international investigator-led clinical trial,conducted within the estimand statistical *** In patients with spontaneous IcH,treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with *** size estimates A sample size of 180 patients(90 in each arm)would be required to detect an absolute difference in the primary outcome of 20%(placebo 39%vs treatment 19%)under a two-tailed significance level of *** adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 *** Participants will receive 1 g intravenous tranexamic acid over 10 min,followed by 1 g intravenous tranexamic acid over 8 hours;or matching *** efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours,defined as either≥33%relative increase or≥6 mL absolute increase in haematoma volume between baseline and follow-up cT *** We describe the rationale and protocol of STOP-MSU,a phase Ⅱ trial of tranexamic acid in patients with IcH within 2 hours from onset,based in participating mobile stroke units and emergency departments.

关键词： placebo centre absolute

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Enhanced saturation magnetization in La^(3+) doped Nico ferrites prepared by sol-gel auto-combustion method

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Journal of Rare Earths 2024年第8期42卷 1546-1554,I0005页

作者： Maddileti Jelli vidyasagar Thopudurthy Krishna Reddy c.v. Department of Physics Rayalaseema UniversityKurnoolA.P518007.Iindia Department of Physics Government PolytechnicRayachotiA.P516269India

Lanthanum doped nickel-cobalt nano ferrites with chemical formula Ni_(0.5)co_(0.5)LaxFe_(2-x)O_(4)(x=0.05,0,10,0.15 and 0,20) were prepared using a simple sol-gel auto combustion *** basic structural properties were determined by X-ray diffraction method and the formation of single phased spinel ferrite was *** crystalline size decreased from 25 to 11 nm and lattice parameter a increases with increase of La *** surface morphology of these ferrites was observed by field-emission scanning electron microscopy(FESEM) and agglomerated irregular grains are observed with increase of the rare earth element La ***-dispersive X-ray spectroscopy(EDX) result confirms the presence of the required *** Fourier transform infrared spectroscopy(FTIR) spectrum indicates the formation of the spinel ferrite structure with M-O *** direct band measurements from ultraviolet-visible spectroscopy(Uv-vis) spectroscopy indicate that the direct band gap decreases from 1.39 to 1.19 ev for x=0.05 to x=0.15,then increases to 1.28 ev for x=*** room temperature magnetic properties of these ferrites were studied by a vibrating sample magnetometer(vSM).The enhanced saturation magnetization of 49.73 emu/g is observed for x=0.10 and then saturation magnetizations are gradually decreased for x=0.15 and x=*** the remanent magnetization and coercivity also follow the same trend.

关键词： Ferrites Sol-gel auto combustion La doping Magnetic properties Rare earths

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Your personal choices in transportation and food are important for lowering carbon emissions

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Frontiers of Environmental Science & Engineering 2024年第6期18卷 27-32页

作者： bruce Logan Fang Zhang Wulin Yang Le Shi Institute of Energy and the Environment The Pennsylvania State UniversityUniversity ParkPA 16802USA School of Environment Tsinghua UniversityBeijing 100084China college of Environmental Sciences and Engineering Peking UniversityBeijing 100871China college of Environmental and Resource Sciences Zhejiang UniversityHangzhou 310058China

There is a global need to reduce greenhouse gas emissions to limit the extent of climate change.A better understanding of how our own activities and lifestyle influence our energy use and carbon emissions can help us enable changes in activities that can lead to reductions in carbon *** we discuss an approach based on examining carbon emissions from the perspective of the unit c,where 1 c is the cO_(2)from food a person would on average eat every *** approach shows that total cO_(2)emissions in china,normalized by the population,is 22.5 c while carbon emissions for a person in the US is 43.9 c.A better appreciation of our own energy use can be obtained by calculating carbon emissions from our own activities in units of c,for example for driving a car gasoline or electric vehicle a certain number of kilometers,using electricity for our homes,and eating different *** this information,we can see how our carbon emissions compare to national averages in different countries and make decisions that could lower our personal cO_(2)emissions.

关键词： carbon dioxide climate change Daily energy Greenhouse gas

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Geochemistry and depositional environment of fuchsite quartzites from Sargur Group,western Dharwar craton,India

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Acta Geochimica 2024年第3期43卷 555-570页

作者： c.S.Sindhuja G.Harshitha c.Manikyamba K.S.v.Subramanyam cSIR(council of Scientific and Industrial Research)-National Geophysical Research Institute(NGRI) Uppal RoadHyderabad 500007India

Meso-Neoarchean fuchsite quartzites are present in different stratigraphic positions of Dharwar craton including the oldest(~3.3 Ga)Sargur Group of western Dharwar *** present study deals with the petro-graphic and geochemical characteristics of the fuchsite quartzites from the Ghattihosahalli belt to evaluate their genesis,depositional setting and the enigma involved in the ancient sedimentation *** major mineral assemblages include quartz,fuchsite,and feldspars along with accessory kyanite and *** geochemical com-positions are characterized by high SiO_(2),Al_(2)O_(3),low MgO,caO,strongly enriched cr(1326–6899 ppm),Ba(1165–3653 ppm),Sr(46–210 ppm),v(107–868 ppm)and Zn(11–158 ppm)contents compared to the upper continental crust(Ucc).The Ucc normalized rare earth element(REE)patterns are characterized by depleted light REE[(La/Sm)Ucc=0.33–0.95]compared to heavy REE[(Gd/Yb)_(Ucc)=0.42–1.65]with conspicuous positive Eu-anomalies(Eu/Eu^(*)=1.35–18.27)characteristic of hydrothermal solutions evidenced through the interlayered *** overall major and trace element systematics reflect a combined mafic-felsic provenance and suggest their deposition at a passive continental margin *** comprehensivefield,petrographic,and geo-chemical studies indicate that these quartzites are infiltrated by cr-richfluids released during high-grade metamorphism of associated ultramafic *** Sargur and the subse-quent Dharwar orogeny amalgamated diverse lithounits from different tectonic settings,possibly leading to the release of cr-richfluids and the formation of fuchsite quartzite during or after the *** sug-gest a pre-existing stable crust prior to the Sargur Group and the link between orogenic events and various mineral deposits in the Dharwar craton.

关键词： Dharwar craton Ghattihosahalli Fuchsite quartzite Provenance Depositional setting

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classification of Rings Associated with the Genus of clean Graphs

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Algebra colloquium 2024年第3期31卷 451-466页

作者： v.Ramanathan c.Selvaraj Aaqib Altaf S.Pirzada Department of Mathematics Periyar UniversitySalem 636011Tamil NaduIndi Department of Mathematics University of KashmirHazratbalSrinagarKashmirIndia

Let R be a ring(not necessarily commutative)with identity 1 and let cL(R)be its clean *** this paper,we investigate the genus number of the compact Riemann surface in which cL(R)can be embedded and explicitly determine all commutative rings R(up to isomorphism)such that cL(R)has genus at most *** is shown that for any Artinian ring R,cL(R)is a projective graph if and only if R is isomorphic to ***,we determine all isomorphism classes of commutative rings whose clean graphs have crosscap two.

关键词： clean graph commutative ring planar graph genus crosscap

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Thermoluminescence characterization of natural and synthetic irradiated ce-monazites

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Journal of Rare Earths 2024年第4期42卷 643-650页

作者： v.correcher c.Boronat J.Garcia-Guinea J.F.Benavente T.Rivera-Montalvo cIEMAT Av.Complutense 4028040MadridSpain MNcN-cSIc J.Gutierrez Abascal 228006MadridSpain Instituto Politécnico Nacional CICATA-IPNAv.Legaria 694Mexico City11500Mexico

The thermoluminescence(TL)emission of synthetic and natural ce-monazites was characterized here to determine the potential application in the identification of microscopic defects from a qualitative point of view trying to link each TL peak to a chemical-physical *** kinetic parameters that lead the luminescence processes were calculated by means of variable heating rate and computing glow curve deconvolution methods and allow identifying three groups of components at~90,130 and 290℃(for the mineral sample)and~90,170,220,270 and 320℃(for the synthetic cePO_(4):Nd_(0.20),La_(0.25)).The main differences appreciated in these complex TL curves are mainly due to(i)the content of impurities(natural sample contains lanthanides as well as U 0.60%and Th 5.22%)and(ii)the degree of crystallinity of the samples which is directly related to the type of impurities(synthetic monazite relies only on Nd and La).The behavior of the dose response in the range of 1-8 Gy is similar for both samples;the TL intensity increases linearly as the dose increases without changes in the position of the maxima,denoting first-order kinetic luminescence *** peak could be mostly associated with structural defects(i.e.,phase transitions),chemical reactions(i.e.,ce3+?ce4+redox reaction,dehydration or dehydroxylation processes)or intrinsic defects(i.e.,Frenkel defects,ODcs or NBOHcs).

关键词： Thermoluminescence Kineticparameters Phosphate ce-monazite Defects Rare earths

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