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Evolving landscape and novel treatments in, metastatic castrate-resistant prostate cancer

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Asian Journal of Andrology 2013年第3期15卷 342-349页

作者： paul J Toren martin E Gleave Department of Urologic Sciences Faculty of Medicine University of British Columbia Vancouver BC V5Z 1M9 Canada

Treatment options for castrate-resistant prostate cancer （CRPC） have advanced in recent years and significantly improved the Outlook for patients with this aggressive and lethal disease. Further understanding of the biology＇of CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor （AR） directed therapy. The treatment landscape is rapidly changing and further biologically rationale, biomarker-based ongoing clinical trials are needed. We review the recent results of major clinical trials in CRPC. New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis, microtubules, chaperones, AR and intracellular kinases, as well as immunotherapy, radiopharmaceuticals and bone-targeted agents. The recent improvement in prognosis for CRPC brings continued optimism for further improvements. Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

关键词： prostate cancer treatment resistance androgen receptor antagonists molecular targets

Rituximab therapy for primary glomerulonephritis: Report on two cases

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World Journal of Clinical Cases 2015年第8期3卷 736-742页

作者： Fabrizio Fabrizi Donata Cresseri Giovanni B Fogazzi Gabriella Moroni Patrizia Passerini paul martin Piergiorgio Messa Division of Nephrology Maggiore Hospital IRCCS Foundation Division of Hepatology School of Medicine University of Miami

The evidence in the medical literature on the efficacy and safety of rituximab therapy for primary glomerulonephritis is limited and controversial. We describe two male Caucasian patients with rapidly progressive kidney failure due to primary proliferative glomerulonephritis. Both of them received high-dose intravenous corticosteroids and oral cyclophosphamide with limited benefit. The first patient(hepatitis C virus-negative mixed cryoglobulinemia) underwent plasma-exchange with intravenous immunoglobulins; he showed significant benefit on kidney function(he became dialysis independent with serum creatinine going back to 1.6 mg/d L) after one rituximab pulse even if urinary abnormalities were still present. No improvement in renal function or urinary changes occurred in the second patient. Both these individuals developed sepsis over the follow-up, the first patient died two months after rituximab therapy. This report is in keeping with the occurrence of severe infections after rituximab therapy in patients with renal impairment at baseline and concomitant high-dose steroids.

关键词： Chronic kidney disease Cryoglobulinemic vasculitis Membranoproliferative glomerulonephritis Rituximab

Endoscopic dilation of complete oesophageal obstructionswith a combined antegrade-retrograde rendezvoustechnique

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World Journal of Gastroenterology 2016年第7期22卷 2366-2372页

作者： Reto Bertolini Christa Meyenberger paul martin Putora Franziska Albrecht martina Anja Broglie Sandro J Stoeckli Michael Christian Sulz Division of Gastroenterology and Hepatology Kantonsspital St.Gallen9007 St.GallenSwitzerland Department of Radiation Oncology Kantonsspital St.Gallen9007 St.GallenSwitzerland Department of Otorhinolaryngology Head and Neck SurgeryKantonsspital St.Gallen9007 St.GallenSwitzerland

AIM: To investigate the combined antegraderetrograde endoscopic rendezvous technique for complete oesophageal obstruction and the swallowing ***: This single-centre case series includes consecutive patients who were unable to swallow due to complete oesophageal obstruction and underwent combined antegrade-retrograde endoscopic dilation(CARD) within the last 10 years. The patients' demographic characteristics, clinical parameters, endoscopic therapy, adverse events, and outcomes were obtained retrospectively. Technical success was defined as effective restoration of oesophageal patency. Swallowing success was defined as either percutaneous endoscopic gastrostomy(PEG)-tube independency and/or relevant improvement of oral food intake, as assessed by the functional oral intake scale(FOIS)(≥ level 3).RESULTS: The cohort consisted of six patients [five males; mean age 71 years(range, 54-74)]. All but one patient had undergone radiotherapy for head and neck or oesophageal cancer. Technical success was achieved in five out of six patients. After discharge, repeated dilations were performed in all five patients. During follow-up(median 27 mo, range, 2-115), three patients remained PEG-tube dependent. Three of four patients achieved relevant improvement of swallowing(two patients: FOIS 6, one patient: FOIS 7). One patient developed mediastinal emphysema following CARD, without a need for ***: The CARD technique is safe and a viable alternative to high-risk blind antegrade dilation in patients with complete proximal oesophageal obstruction. Although only half of the patients remained PEG-tube independent, the majority improved their ability to swallow.

关键词： Oesophageal obstruction Rendezvoustechnique Combined antegrade-retrograde endoscopicdilation Endoscopic dilation Head and neck cancer Radiotherapy

The impact of nucleos(t)ide analog therapy in hepatitis B on the incidence of hepatocellular carcinoma: an update including recent literature findings

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Hepatoma Research 2017年第12期3卷 302-308页

作者： Walid SAyoub Francis Dailey paul martin Patricia DJones Department of Gastroenterology and Hepatology Cedars Sinai Medical CenterLos AngelesCA90048USA David Geffen School of Medicine University of California Los AngelesLos AngelesCA90095USA Division of Hepatology Department of MedicineUniversity of Miami Miller School of MedicineUniversity of MiamiMiamiFL33136USA Sylvester Comprehensive Cancer Center University of MiamiMiamiFL33136USA.

Worldwide, hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality. In men, it is the fifth most common cancer and seventh most common in women;HCC is the second highest cause of cancer-related death worldwide. It is less prevalent in the USA and Northern Europe and more prevalent in Eastern and South-Eastern Asia. Over 700,000 cases are diagnosed each year - half of which occur in China - and result in roughly the same number of deaths per year. HCC significantly impairs quality of life and is associated with great costs to society. It is estimated that half of the deaths from HCC are associated with hepatitis B virus (HBV). Fortunately, HBV vaccination and antiviral therapy have shown excellent efficacy in decreasing the incidence of HCC. We will discuss the relationship of HBV to HCC, address available treatments for HBV and the impact of treatment on the development of HCC.

关键词： Liver cancer hepatocellular carcinoma hepatitis B nucleos(t)ides entecavir tenofovir lamivudine

Clinical Outcome Event Adjudication in a 10-Year Prospective Study of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B

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Journal of Clinical and Translational Hepatology 2020年第4期8卷 377-384页

作者： Joseph K Lim Alex Y Chang Atif Zaman paul martin Conrado M Fernandez-Rodriguez Mete Korkmaz Simona Rossi James M Ford Tamara Noonan Elizabeth Cooney Victor Navarro Luis Colombato Yale University School of Medicine New HavenCTUSA Johns Hopkins School of Medicine BaltimoreMDUSA and Johns Hopkins SingaporeSingapore Oregon Health&Science University PortlandORUSA University of Miami Miller School of Medicine MiamiFLUSA Hospital Universitario Fundación Alcorcón MadridSpain OSF Saint Anthony Center for Cancer Care RockfordILUSA Einstein Healthcare Network PhiladelphiaPAUSA Stanford University School of Medicine StanfordCAUSA Bristol-Myers Squibb WallingfordCTUSA Hospital Británico UCA School of MedicineBuenos AiresArgentina

Background and Aims:In the REALM (Randomized, Obser-vational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Pa-tients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progres-sion events, and deaths. An external event adjudication com-mittee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize poten-tial adverse effects of the large cohort, interdisciplinary out-come assessments, geographic scope, and long duration. Methods:The EAC comprised an international group of hep-atologists and oncologists with expertise in diagnosis of tar-geted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria cap-tured in the EAC charter. Operational processes, including da-ta collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%;hepatocellular carcino-ma (HCC), 83.3%;non-HCC malignancies, 88.0%;non-HCC HBV disease progression, 68.2%. Reasons for lack of con-cordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consis-tency;EAC performance was facilitated by well-defined diag-nostic criteria, effective data capture, and efficient operational processes. Trial registration: *** NCT00388674.

关键词： Hepatitis B Antiviral therapy Clinical outcomes Event adjudication Liver cirrhosis

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802·11n助连接生活驶入快车道

世界电子元器件 2007年第9期 28-31页

作者： paul martin 恩智浦半导体公司家庭娱乐事业部

对于消费者来说，如果他们有其他方式可以轻松迅速地复制数字内容，他们肯定不会在家里布线建立一个以太网或局域网来传送数字内容。然而，随着无线技术的迅猛发展，部署快、安装成本低、配置灵活以及无线网络的其他优势已经被人们广泛... 详细信息

对于消费者来说，如果他们有其他方式可以轻松迅速地复制数字内容，他们肯定不会在家里布线建立一个以太网或局域网来传送数字内容。然而，随着无线技术的迅猛发展，部署快、安装成本低、配置灵活以及无线网络的其他优势已经被人们广泛接受了。

关键词：快车道生活连接数字内容无线技术无线网络消费者局域网

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RRI-STEPTM带来全新突破

汽车制造业 2012年第23期 50-50,52页

作者： paul martin 英莳精密部件有限公司

汽车行业在不断寻求轻量化的解决方案，以提高车辆的续航历程、燃油效率和整体性能。以往厂商们的重点主要放在降低大型部件的重量上，现在人们已越来越多地开始考虑如何降低包括紧固件在内的这些小型组件的重量了。

关键词： M带汽车行业燃油效率大型部件轻量化紧固件重量

Late Mesozoic rifting and its deep dynamic mechanisms in the central Sulu orogenic belt: Records from Lingshan Island

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Science China Earth Sciences 2022年第9期65卷 1751-1771页

作者： Tengfei ZHOU Yaoqi ZHOU Nina SФAGER paul martin HOLM Zhenkai ZHANG Jun WANG Zhao LIANG Hongyu MU Yanjun CHENG Feifei LIU Miao WANG Yue ZHANG Hui ZHANG Yangjian GU Shihui DONG Hanjie ZHAO Manjie LI Yang CHEN Yanzi LIU School of Geosciences China University of Petroleum(East China)Qingdao 266580China Department of Geosciences and Natural Resource Management University of CopenhagenCopenhagen-K 1350Denmark Shandong Provincial Key Laboratory of Deep Oil&Gas China University of Petroleum(East China)Qingdao 266580China Shaanxi Center of Mineral Geological Survey Shaanxi Institute of Geological SurveyXi'an 710068China School of Earth Sciences Yunnan UniversityKunming 650500China Department of Science and Technology Hebei GEO UniversityShijiazhuang 050031China College of Earth Science and Engineering Shandong University of Science and TechnologyQingdao 266590China School of Architectural Engineering Binzhou UniversityBinzhou 256500China Research Institute of Petroleum Exploration and Development Shengli Oilfield CompanySINOPECDongying 257015China Key Laboratory of Geological Safety of Coastal Urban Underground Space Ministry of Natural ResourcesQingdao Geo-Engineering Surveying InstituteQingdao 266101China

The Lingshan Island scientific drill confirms that two episodes(Laiyang period and Qingshan period) of rifting developed in the central Sulu orogenic belt(SOB) in Late Mesozoic. With a set of methods including fieldwork, drilling, core logging, zircon U-Pb dating and whole rock geochemistry applied, the age, the depositional sequence and the deep dynamic mechanisms of rift evolution were unraveled. The stratigraphic sequence of the Laiyang-Qingshan Groups on Lingshan Island was composed of two different rifting sequences:(1) Laiyang Group(147–125 Ma), which consists of deep-water gravity flow deposits with interlayers of intermediate volcanic rocks;and(2) Lower Qingshan Group(125–119 Ma), which unconformably overlies the former sequence and contains subaerial volcanic deposits and terrestrial deposits. The tectonic environment changed during the evolution of these two episodes of rifting: the rift was in a NNW-SSE extensional environment in the Laiyang period and showed the typical passive rifting character that “lithospheric extension and rifting preceded volcanism”. The passive rifting period was ended by a short WNW-ESE compression at about 125 Ma. After that, the tectonic environment transferred to a strong NW-SE extensional environment and the rifting evolved into a volcanic arc basin in the Qingshan period. The igneous rocks are shoshonitic to high-K calc-alkaline trachyandesites to trachytes with a few intercalated lamprophyres and a *** geochemical characteristics of the igneous rocks indicate that they are mantle-derived melts with a metasomatized mantle source and/or crustal contamination. In addition, an increased thinning of the lithosphere happened during the rifting *** low-angle subduction of the Paleo-Pacific plate in the Jurassic weakened the thickened SOB lithospheric mantle. The rollback of the subducting plate started in late Jurassic to early Cretaceous, and the SOB lithospheric mantle was delaminated synchronously because of t

关键词： Sulu orogenic belt Lingshan Island Late Mesozoic Rifting Slab subduction Basin dynamics

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行为测量入门指南，第三版

国外科技新书评介 2008年第12期 22-23页

作者： paul martin（）李少霞不详中国科学院力学研究所博士生

本书是第三版，本版在前两版的基础上作了较大的改动，对研究规划和数据解释和陈述部分增加了许多新内容，但主要内容仍然是行为定量研究原理和方法，重点介绍了观测技术、记录方法和分析方法。

关键词：第三版行为测量指南入门数据解释观测技术记录方法