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Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-Ⅱ (TRACE Ⅱ): rationale and design

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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Immune Regulatory Cell Biology and Clinical Applications to Prevent or Treat Acute Graft-Versus-Host Disease

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Engineering 2019年第1期5卷 98-105页

作者： bruce R. Blazar Masonic Cancer Center & Division of Blood and Marrow Transplantation Department of Pediatrics University of Minnesota Minneapolis MN 55455 USA

The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients functionally T cell deficient and hence highly susceptible to infections and tumor recurrence. Depletion is often accomplished through the use of broadly reactive antibodies, while functional impairment is typically achieved by pharmacological agents that require long-term administration (usually six months or more), have significant side effects, and may not result in tolerance (i.e., nonresponsiveness) of donor T cells to conditioning regimen-resistant host alloantigen-bearing cells. As our knowledge of immune system homeostasis has increased, cell populations with immune regulatory function have been identified and characterized. Although such cell populations are typically present in low frequencies, methods to isolate and expand these cells have permitted their supplementation to the donor graft or infusion late post-transplant in order to stifle GVHD. This review discusses the biology and preclinical proof of concept of GVHD models, along with GVHD outcomes that focus exclusively on immune regulatory cell therapies that have progressed to clinical testing.

关键词： Graft-versus-host disease (GVHD) Immune regulatory cells Cell therapy

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A new perspective on quiet Sun magnetism

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Science China(Physics,Mechanics & Astronomy) 2009年第11期52卷 1660-1664页

作者： LITES bruce William High Altitude Observatory National Center for Atmospheric ResearchP.O. Box 3000 Boulder CO 80307 USA

The Hinode mission has provided us with a new, quantitative view of the magnetism of the quiet Sun. It has revealed that the quiet internetwork areas are blanketed by horizontal fields that appear at first sight to have more flux than the vertical fields resolved on the same 0.3 size scale. These measurements point to the possibility that the horizontal fields might be the primary source of the "hidden turbulent flux" of the quiet Sun anticipated from Hanle effect depolarization. In this paper, evidence is presented suggesting that the "seething" horizontal fields observed by Harvey in 2007 and the horizontal fields revealed by Hinode are the same phenomenon. Because the seething fields appear to be of uniform fluctuation over the whole disk, the phenomenon is most likely not associated with the dynamo source of solar activity. Thus, the small-scale "hidden turbulent flux" lends support to the notion of a local solar dynamo acting on granular sizes and time scales.

关键词： Sun magnetism fields granulation

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Alcoholic hepatitis 2010:A clinician's guide to diagnosis and therapy

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World Journal of Gastroenterology 2010年第39期16卷 4905-4912页

作者： Maziyar Amini bruce A Runyon Department of Gastroenterology and Hepatology Loma Linda University Medical Center

Alcoholic hepatitis(AH)remains a common and life threatening cause of liver failure,especially when it is *** the adjective"acute"is frequently used to describe this form of liver injury,it is usually subacute and has been developing for weeks to months before it becomes clinically *** with this form of alcoholic liver disease usually have a history of drinking heavily for many *** certain aspects of therapy,mainly nutritional support and abstinence are well established,significant debate has surrounded the pharmacologic treatment of AH,and many institutions practice widely varying treatment protocols. In recent years a significant amount of literature has helped focus on the details of treatment,and more data have accumulated regarding risks and benefits of pharmacologic *** particular,the efficacy of pentoxifylline has become increasingly apparent,and when compared with the risks associated with prednisolone,has brought this drug to the forefront of therapy for severe *** review will focus on the clinical and laboratory diagnosis and pharmacologic therapies that should be applied during hospitalization and continued into outpatient *** conclude that the routine use of glucocorticoids for severe AH poses significant risk with equivocal benefit,and that pentoxifylline is a better,safer and cheaper *** the full details of nutritional support lie beyond the scope of this article,nutrition is a cornerstone of therapy and must be addressed in every patient diagnosed with AH. Finally,while traditional psychosocial techniques play a major role in post-hospitalization care of alcoholics, we hope to make the medical clinician realize his or her role in reducing recidivism rates with early and frequent outpatient visits and with the use of baclofen to reduce alcohol craving.

关键词： Alcoholic hepatitis Alcoholic liver disease Pentoxifylline Baclofen

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Quantification of soluble epoxide hydrolase inhibitors in experimental and clinical samples using the nanobody-based ELISA

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Journal of Pharmaceutical Analysis 2023年第9期13卷 1013-1023页

作者： Huiyi Yang Meng Qi Qiyi He Sung Hee Hwang Jun Yang Mark McCoy Christophe Morisseau Suqing Zhao bruce D.Hammock Department of Pharmaceutical Engineering School of Biomedical and Pharmaceutical SciencesGuangdong University of TechnologyGuangzhouChina Department of Entomology and Nematology and UCD Comprehensive Cancer Center University of CaliforniaDavisCA 95616USA Langfang Normal University LangfangHebei065000China

To ensure proper dosage of a drug,analytical quantification of it in biofluid is *** chromatography mass spectrometry(LC-MS)is the conventional method of choice as it permits accurate identification and ***,it requires expensive instrumentation and is not appropriate for bedside *** soluble epoxide hydrolase(sEH)inhibitors(EC5026 and TPPU)as examples,we report development of a nanobody-based enzyme-linked immunosorbent assay(ELISA)for such small molecules and its use to accurately quantify the drug chemicals in human *** optimized conditions,two nanobody-based ELISAs were successfully established for EC5026 and TPPU with low limits of detection of 0.085 ng/mL and 0.31 ng/mL,respectively,and two order of magnitude linear ranges with high precision and *** assay was designed to detect parent and two biologically active metabolites in the investigation of a new drug candidate *** addition,the ELISAs displayed excellent correlation with LC-MS analysis and evaluation of inhibitory *** results indicate that nanobody-based ELISA methods can efficiently analyze drug like *** methods could be easily implemented by the bedside,in the field in remote areas or in veterinary *** work illustrates that nanobody based assays offer alternative and supplementary analytical tools to mass spectrometry for monitoring small molecule medicines during clinical development and *** of nanobody based pharmaceutical assays are discussed.

关键词： Nanobody Immunoassay Soluble epoxide hydrolase inhibitors Metabolites Small molecules

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Severe and Prolonged Hypocalcaemia Post Zoledronic Acid Infusion in a Patent with Sleeve Gastrectomy

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Journal of Biosciences and Medicines 2022年第9期10卷 174-181页

作者： Andrew Jeyaruban bruce Hall Department of Renal Medicine Liverpool Hospital Sydney Australia

Background: Zoledronic acid is commonly used to treat hypercalcaemia and osteoporosis, as well as to prevent skeletal complications from haematological and solid organ malignancies. Case presentation: We report the case of a 38 year old lady who presented with severe hypocalcaemia following the administration of zoledronic acid. Her significant background history included vitamin D deficiency and sleeve gastrectomy three years ago. She had prolonged hypocalcaemia requiring IV calcium replacement for two months. Her prolonged hypocalcaemia was attributed to her vitamin D deficiency at the time of zoledronic acid infusion as well as her history of bariatric surgery. Conclusion: This case emphasises the importance of ensuring vitamin D levels are replete prior to zoledronic acid infusion and ensuring the calcium levels are checked frequently in patients with a history of bariatric surgery obtaining zoledronic acid.

关键词： Hypocalcaemia Zoledronic Acid Bariatric Surgery

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One-Dimensional Nonlinear Laplacians under a 3-Point Boundary Condition

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Acta Mathematica Sinica,English Series 2010年第9期26卷 1641-1652页

作者： bruce D.CALVERT Department of Mathematics University of Auckland

We consider a three-point boundary value problem for operators such as the one-dimensional p-Laplacian, and show when they have solutions or not, and how many. The inverse operators are given by various formulas involving zeros of a real-valued function. They are shown to be orderpreserving, for some parameter values, and non-singleton valued for others. The operators are shown to be m-dissipative in the space of continuous functions.

关键词： Boundary value problems nonlinear o.d.e.s p-Laplacian three-point boundary value problem m-dissipative

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A new alternative approach for investigating acidization dissolution front propagation in fluid-saturated carbonate rocks

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Science China(Technological Sciences) 2017年第8期60卷 1197-1210页

作者： ZHAO ChongBin HOBBS bruce ORD Alison Computational Geosciences Research Centre Central South University School of Earth and Environment The University of Western Australia

The natural phenomenon associated with the chemical dissolution of dissolvable minerals of rocks can be employed to develop innovative technology in mining and oil extracting *** paper presents a new alternative approach for theoretically dealing with chemical dissolution front(CDF) propagation in fluid-saturated carbonate *** that the CDF is represented by the porosity front in this *** this new approach,the porosity,pore-fluid velocity and acid concentration are directly used as independent *** illustrate how to use the present new approach,an acidization dissolution system(ADS) consisting of carbonate rocks,which belongs to one of the many general chemical dissolution systems(CDSs),is taken as an application *** the acid dissolution capacity(ADC) number(that is defined as the ratio of the volume of the carbonate rock dissolved by an acid to that of the acid) approaches zero,the present new approach can be used to obtain analytical solutions for the stable ***,if the ADC number is a nonzero finite number,then numerical solutions can be only obtained for the ADS,especially when the ADS is in an unstable *** related theoretical results have demonstrated that:(1) When the ADS is in a stable state and in the case of the ADC number approaching zero,the present new approach is mathematically equivalent to the previous approach,in which the porosity,pore-fluid pressure and acid concentration are used as independent ***,when the ADS is in an unstable state,the use of the present new approach leads to a free parameter that needs to be determined by some other ways.(2) The existence of a non-step-type dissolution front within a transient region should at least satisfy that none of the ADC number,injected acid velocity and reciprocal of the dissolution reaction rate is equal to zero in the stable ADS.

关键词：化学溶解碳酸盐岩流体饱和传播不稳定状态酸化孔隙流体压力流体速度

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A unified theory for sharp dissolution front propagation inchemical dissolution of fluid-saturated porous rocks

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Science China(Technological Sciences) 2019年第1期62卷 163-174页

作者： ZHAO ChongBin HOBBS bruce ORD Alison Computational Geosciences Research Centre Central South University School of Earth and Environment The University of Western Australia

This paper presents a unified theory to deal with when, why and how a sharp acidization dissolution front(ADF), which is represented by the porosity distribution curve, can take place in an acidization dissolution system composed of fluid-saturated porous rocks. The theory contains the following main points:(1) A reaction rate of infinity alone can lead to a sharp ADF of the Stefan-type in the acidization dissolution system. This sharp front is unstable when permeability in the downstream region is smaller than that in the upstream region.(2) For a finite reaction rate, when the acid dissolution capacity number approaches zero,the ADF can have a sharp profile of the Stefan-type either on a much smaller time scale or on a much larger time scale than the dissolution time scale. In the former case, the ADF may become unstable on a much larger time scale than the transport time scale, while in the latter case, it may become unstable if the growth rate of a small perturbation is greater than zero.(3) On the dissolution time scale, even if both the reaction rate is finite and the acid dissolution capacity number approaches zero, the profile of an ADF may not be sharp because it is in a transient state. In this case, not only can an ADF change its profile with time, but also its morphology can grow if the growth rate of a small perturbation is greater than zero. Due to the involvement of both the change rate and the growth rate of the ADF profile, it is necessary to conduct a transient linear stability analysis for determining whether or not a time-dependent ADF is stable in the acidization dissolution system.

关键词： sharp dissolution front stationary/steady state transient state acid dissolution capacity acidization dissolution porous rocks

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Effects of porosity heterogeneity on chemical dissolution-front instability in fluid-saturated rocks

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Journal of Central South University 2017年第3期24卷 720-725页

作者：赵崇斌 Peter SCHAUBS bruce HOBBS Computational Geosciences Research Centre Central South University Changsha 410083 China CSIRO Mineral Resource National Research Flagship P. O. Box 1130 Bentley WA 6102 Australia School of Earth and Environment The University of Western Australia Crawley WA 6009 Australia

Homogeneity and heterogeneity are two totally different concepts in *** the particle length scale,rocks exhibit strong heterogeneity in their constituents and *** the heterogeneity of porosity obeys the random uniform distribution,both the mean value and the variance of porosities in the heterogeneous porosity field can be used to reflect the overall heterogeneous characteristics of the porosity *** main purpose of this work is to investigate the effects of porosity heterogeneity on chemical dissolution front instability in fluid-saturated rocks by the computational simulation *** related computational simulation results have demonstrated that:1) since the propagation speed of a chemical dissolution front is inversely proportional to the difference between the final porosity and the mean value of porosities in the initial porosity field,an increase in the extent of the porosity heterogeneity can cause an increase in the mean value of porosities in the initial porosity field and an increase in the propagation speed of the chemical dissolution front.2) An increase in the variance of porosities in the initial porosity field can cause an increase in the instability probability of the chemical dissolution front in the fluid-saturated rock.3) The greater the mean value of porosities in the initial porosity field,the quicker the irregular morphology of the chemical dissolution front changes in the supercritical chemical dissolution *** means that the irregular morphology of a chemical dissolution front grows quicker in a porosity field of heterogeneity than it does in that of homogeneity when the chemical dissolution system is at a supercritical stage.

关键词：化学溶解饱和岩石非均质性孔隙度不稳定性初始孔隙率计算机模拟前缘

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