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Gastrointestinal stromal tumor and its targeted therapeutics

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chinese Journal of cancer 2011年第5期30卷 303-314页

作者： Jheri Dupart Jonathan c.trent Departments of Sarcoma Medical Oncology and Pathology The University of Texas MD Anderson Cancer Center

Over the past 60 years,investigators of basic science,pathology,and clinical medicine have studied gastrointestinal stromal tumor(GIST) and made minor advances in patient care.Recent discoveries have led to an understanding of the biological role of KIT and platelet-derived growth factor receptor-α in GIST and the development of the tyrosine kinase inhibitor imatinib mesylate(Gleevec,formerly STI-571),one of the most exciting examples of targeted therapy to date.The success of targeted therapy in GIST has lead to new developments in our understanding of the medical and surgical management of the disease.Intense study of GIST may lead to new paradigms in the management of cancer.

关键词：靶向治疗胃肠道间质血小板衍生生长因子酪氨酸激酶抑制剂生物学作用基础科学临床医学

The favorable impact of PIK3cA mutations on survival: an analysis of 2587 patients with breast cancer

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chinese Journal of cancer 2012年第7期31卷 327-334页

作者： Amaury G. Dumont Sarah N.Dumont Jonathan c. trent Department of Experimental Pediatrics University of Texas-MD Anderson Cancer CenterHouston Texas United States Division of Hematology and Oncology University of Miami-Sylvester Comprehensive Cancer CenterMiami Florida United States

The phosphatidylinositol-3 kinase(PI3K) pathway regulates a number of cellular processes, including cell survival, cell growth, and cell cycle progression. consequently, this pathway is commonly deregulated in cancer. In particular, mutations in the gene PIK3cA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast tumors in transgenic mice. These data underscore the role of this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway. However, conflicting data suggest that gain-of-function PIK3cA mutations may be associated with either a favorable or a poor clinical outcome, compared with the wild-type PIK3cA gene. In the current study, we performed a systematic review of breast cancer clinical studies. Upon evaluation of 2587 breast cancer cases from 12 independent studies, we showed that patients with tumors harboring a PIK3cA mutation have a better clinical outcome than those with a wild-type PIK3cA gene. Importantly, this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer. We propose three potential explanations for this paradoxical observation. First, PIK3cA mutations may interfere with the metastasis process or may induce senescence, which results in a better outcome for patients with mutated tumors. Secondly, we speculate that PIK3cA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells. Lastly, we propose that PIK3cA mutations may be a favorable predictive factor for response to hormonal therapy, giving a therapeutic advantage to these patients. Ultimately, an improved understanding of the clinical impact of PIK3cA mutations is critical for the development of optimally personalized therapeutics against breast cancer and other solid tumors. This effort will be

关键词：肿瘤患者乳腺癌突变转基因小鼠肌动蛋白细胞骨架磷脂酰肌醇-3 信号通路乳腺肿瘤

Warming but not thawing of the cold permafrost in northern Alaska during the past 50 years

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Research in cold and Arid Regions 2009年第1期1卷 1-13页

作者： Max c. brewer State Key Laboratory of Frozen Soils Engineering cold and Arid Regions Environmental and Engineering Research Institute chinese Academy of Sciences U. S. Geological Survey 4200 University Drive

climate warming has not resulted in measurable thawing of the cold (–5°c to –10°c) permafrost in northern Alaska during the last half century. The maximum depths of summer thaw at five locations near Barrow, Alaska, in 2005 were within the ranges of the depths obtained at those same locations during the early 1950s. However, there has been a net warming of about 2°c, after a cooling of 0.4°c during 1953–1960, at the upper depths of the permafrost column at two of the locations. Thawing of permafrost from above (increase in active layer thickness) is determined by the summer thawing index for the specific year; any warming, or cooling, of the upper permafrost column results from the cumulative effect of changes in the average annual air temperatures over a period of years, assuming no change in surface conditions. Theoretically, thawing from the base of permafrost should be negligible even in areas of thin (about 100–200 m) permafrost in northern Alaska. The reported shoreline erosion along the northern Alaska coast is a secondary result from changes in the adjacent ocean ice coverage during the fall stormy period, and is not directly because of any 'thawing' of the permafrost.

关键词： cold permafrost climate change thawing northern Alaska

Highway Roadway Stability Influenced by Warm Permafrost and Seasonal Frost Action:A case Study from Glennallen,Alaska,USA

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Research in cold and Arid Regions 2008年第1期 26-41页

作者： Max c.brewer Professor Emeritus of Arctic Environments and Engineering US Geological SurveyAnchorageAlaska 99508USA

Ground temperatures from four of the seven extensively studied highway cross-sections near Gulkana/Glennallen,Alaska during 1954;962,were chosen to better understand the impacts of highway construction on warm permafrost.Both the thawing of permafrost and seasonal frost action impacted on road surface stability for about 6 years until the maximum summer thaw reached about 3 m in depth.Seasonal frost action caused most of the ensuing stability problems.Unusually warm summers and the lengths of time required to re-freeze the active layer were far more important than the average annual air temperatures in determining the temperatures of the underlying shallow permafrost,or the development of taliks.The hypothesized climate warming would slightly and gradually deepen the active layer and the developed under-lying talik,but its effect would be obscured by unusually warm summers,by warmer than usual winters,and by the vari-able lengths of time of the zero curtains.At least one period of climate mini-cooling in the deeper permafrost during the early 20th century was noted.

关键词： warm permafrost active layer seasonal frost action zero curtain talik roadway climate warming

Ductile Thrusting-shearing Genesis of Hongzhen Granitoid, Anhui Province

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chinese Journal Of Geochemistry 1994年第3期13卷 236-245页

作者：张开均黄钟瑾施央申黄良书乔烈光 R.c.brewer Department of Earth Sciences Nanjing University Nanjing Department of Geology University of Alabama Tuscaloosa USA Geological Team 326 of Geological Bureau of Anhui Province Anqing

As view from the petrological, mineralogical and petrochemical studies, the Hongzhen granitoid is characterized by the autichthonous-parautochthonous transformation. The source rocks are mainly felsic clastic sediments with a small amount of intermediate magmatite in the Zhangbaling Group.The granitoid is covered by mylonite and migmatite, and the three rocks share much in common with respect to their REE distribution pattems and the W-type distribution of transition elements,indicating that they all came from identical souree rocks. The granitoid belongs to collision granites or post-orogenic granitoids resulting from ductile thrusting-shearing under 550℃ and 7 × 108 Pa conditions in the foreland of the Yangtze plate during the Late Indosinian movement, and from metasomatism plus partial melting.

关键词：花岗岩糜棱岩混合岩安徽柔韧剪切带

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 unclear.Here,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 onset.The primary outcome was a shift in scores on the modified Rankin scale(mRS)at day 90.Secondary 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’markers.Data were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%cI.Results 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]min.Neuroimaging‘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 stroke.conclusions 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 trials.WHAT IS ALREADY KNOWN ON THIS TOPIc⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those with acute stroke treated within 6hours of stroke

关键词： Glasgow nitrate random

Fully integrated and broadband Si-rich silicon nitride wavelength converter based on Bragg scattering intermodal four-wave mixing

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Photonics Research 2024年第3期12卷 I0001-I0010页

作者： VALERIO VITALI THALÍA DOMÍNGUEZ BUcIO HAO LIU JOSÉMANUEL LUQUE GONZÁLEZ FRANcIScO JURADO-ROMERO ALEJANDRO ORTEGA-MOÑUX GLENN cHURcHILL JAMES c.GATES JAMES HILLIER NIKOLAOS KALFAGIANNIS DANIELE MELATI JENS H.ScHMID ILARIA cRISTIANI PAVEL cHEBEN J.GONZALO WANGÜEMERT-PÉREZ ÑIGO MOLINA-FERNÁNDEZ FREDERIc GARDES cOSIMO LAcAVA PERIKLIS PETROPOULOS Optoelectronics Research centre University of SouthamptonSouthampton SO171BJUK 2ElectricalComputer and Biomedical Engineering DepartmentUniversity of PaviaPavia 27100Italy 3Telecommunication Research Institute(TELMA)Universidad de MálagaCEI Andalucı´a TECHE.T.S.I.Telecomunicación29010 MálagaSpain 4School of Science and TechnologyNottingham Trent UniversityNottingham NG118NSUK 5Department of Electrical EngineeringEindhoven University of TechnologyEindhoven 5600 MBThe Netherlands 6Department of Materials Science and EngineeringUniversity of IoanninaIoannina 45110Greece 7Centre de Nanosciences et de NanotechnologiesUniversitéParis-SaclayCNRS91120 PalaiseauFrance 8Advanced Electronics and Photonics Research CenterNational Research Council CanadaOttawaOntario K1A 0R6Canada

Intermodal four-wave mixing(FWM)processes have recently attracted significant interest for all-optical signal processing applications thanks to the possibility to control the propagation properties of waves exciting distinct spatial modes of the same waveguide.This allows,in principle,to place signals in different spectral regions and satisfy the phase matching condition over considerably larger bandwidths compared to intramodal processes.However,the demonstrations reported so far have shown a limited bandwidth and suffered from the lack of on-chip components designed for broadband manipulation of different modes.We demonstrate here a silicon-rich silicon nitride wavelength converter based on Bragg scattering intermodal FWM,which integrates mode conversion,multiplexing and de-multiplexing functionalities on-chip.The system enables wavelength conversion between pump waves and a signal located in different telecommunication bands(separated by 60 nm)with a 3 dB bandwidth exceeding 70 nm,which represents,to our knowledge,the widest bandwidth ever achieved in an intermodal FWM-based system.

关键词： scattering pump modal

A mixed method analysis of patients' complaints: Underpinnings of theory-guided strategies to improve quality of care

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International Journal of Nursing Sciences 2018年第4期5卷 377-382页

作者： Holly Wei Yan Ming Hong cheng Hui Bian Jie Ming trent L.Wei East carolina University college of Nursing GreenvilleNCUSA The Affiliated Hospital of Qingdao University QingdaoChina East carolina University GreenvilleNCUSA Duke University Medical center DurhamNCUSA

Purpose:Patients'complaints can be predictors of patient care quality and safety.Understanding patients'complaints could help healthcare organizations target the areas for improvements.The purpose of this study is to use a mixed method analysis to a)examine the characteristics and categories of patients'complaints,b)explore the relationships of patients'complaints with professions and units,and c)propose theory-based strategies to improve care quality.Methods:This is a descriptive mixed method study.Data examined are patients'complaints filed at a university-affiliated hospital in china from January 2016 to December 2017.A qualitative content analysis was conducted to categorize complaints.A TwoStep cluster analysis was performed to provide an overall profile of patients'complaints.chi-Square tests were conducted to investigate the relationships among complaints,professions,and units.Results:838 complaints were filed,with 821 valid cases for analysis.Six categories surfaced from the qualitative analysis:uncaring attitudes,unsatisfactory quality of treatment or competence,communication problems,the process of care,fees and billing issues,and other miscellaneous causes.Physicians received most of the complaints(56.6%).The unit receiving the most complaints were outpatient clinics and medical support units(52.7%).The cluster analysis indicated four distinct clusters.Significant relationships existed between complaints and professions(x2(20)=178.82,Pcomplaints and units(x2(15)=42.72,Pconclusions:Patients'complaints are valuable sources for quality improvements.Healthcare providers should be not only scientifically knowledgeable,but also humanistic caring.caring-based theories may provide guidance in clinical practice.

关键词： Patient complaints Patient safety Quality improvements Quality of health care

Semiconducting carbon Nanotube/Fullerene Blended Heterojunctions for Photovoltaic Near-Infrared Photon Harvesting

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Nano Research 2011年第11期4卷 1174-1179页

作者： Dominick J. Bindl Adam S. brewer Michael S. Arnold 1509 University Ave. Materials Science and Engineering Dept. University of Wisconsin-Madison Madison WI 53706 USA

我们证明在红外线附近(NIR ) 半导体的围单人赛的碳 nanotubes (s-SWcNTs ) 的吸收率能与 fullerene 衍生物在混合异质接面被利用[6,6 ]-phenyl-c61-butyric 酸甲基酉旨(PcBM ) 。Photogenerated 费用分离高效地被驾驶由超离频在二材料... 详细信息

我们证明在红外线附近(NIR ) 半导体的围单人赛的碳 nanotubes (s-SWcNTs ) 的吸收率能与 fullerene 衍生物在混合异质接面被利用[6,6 ]-phenyl-c61-butyric 酸甲基酉旨(PcBM ) 。Photogenerated 费用分离高效地被驾驶由超离频在二材料之间的混合和有利精力偏移量的界面的区域。NIR 敏感光电并且利用栈的光电探测器设备(铟听 oxide/ca。10 nm s-SWcNT : PcBM/100 nm c60/10 nm 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BcP )/Ag ) 与 NIR 力量变换效率被制作 >1.3% 并且山峰，零偏爱在 = 的 18% 的外部量效率 1205 nm。

关键词：半导体碳纳米管富勒烯衍生物近红外混合物异质结单壁碳纳米管收获光子