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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng Zhang richard jones Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer ***: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day *** samples were obtained on d 1 and d 28. Clinical responses were assessed every eight ***: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 ***: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

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Surgical management of the diabetic foot:The current evidence

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World Journal of Orthopedics 2024年第5期15卷 404-417页

作者： richard Henry Randall Roberts Gareth Rhys Davies-jones James Brock Vaishnav Satheesh Greg AJ Robertson Department of Trauma and Orthopaedics Wrexham Maelor HospitalWrexham LL137TDUnited Kingdom Department of Trauma and Orthopaedics The Robert Jones and Agnes Hunt Orthopaedic HospitalOswestry SY107AGUnited Kingdom

The prevalence of diabetes mellitus and its associated complications,particularly diabetic foot pathologies,poses significant healthcare challenges and economic burdens *** review synthesises current evidence on the surgical management of the diabetic foot,focusing on the interplay between neuropathy,ischemia,and infection that commonly culminates in ulcers,infections,and,in severe cases,*** escalating incidence of diabetes mellitus underscores the urgency for effective management strategies,as diabetic foot complications are a leading cause of hospital admissions among diabetic patients,significantly impacting morbidity and mortality *** review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers,infections,and skeletal pathologies such as Charcot arthropathy,emphasising the critical role of early diagnosis,comprehensive management strategies,and interdisciplinary care in mitigating adverse *** addressing surgical interventions,this review evaluates conservative surgeries,amputations,and reconstructive procedures,highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot *** integration of advanced diagnostic tools,novel surgical techniques,and postoperative care,including offloading and infection control,are discussed in the context of optimising healing and preserving limb function.

关键词： Diabetes Diabetic foot Charcot Osteomyelitis Amputation Diabetic foot attack Conservative surgery

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A subfossil chironomid-total phosphorus inference model for lakes in the middle and lower reaches of the Yangtze River

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Chinese Science Bulletin 2006年第17期51卷 2125-2132页

作者： ZHANG Enlou Alan Bedford richard jones SHEN Ji WANG Sumin TANG Hongqu Nanjing Institute of Geography & Limnology Chinese Academy of Sciences Nanjing 210008 China Natural Geographical and Applied Sciences Edge Hill College Ormskirk L394QP England Department of Geography University of Exeter Exeter EX4 4RJEngland School of Biology Nankai University Tianjin 300017 China

The results of an investigation into the relationship between surface sediment subfossil chi- ronomid distribution and water quality are presented. Data from 30 lakes in the middle and lower reaches of the Yangtze River indicate that the nutrient gradi- ent was the major factor affecting the distribution of chironomids across these sites. Canonical corre- spondence analysis (CCA) revealed that of 12 sum- mer water environmental variables, total Phosphorus was most important, accounting for 20.1% of the variance in the chironomid data. This was significant enough to allow the development of quantitative in- ference models. A TP inference model was devel- oped using weighted averaging (WA), partial least squares (PLS) and weighted averaging partial least squares (WA-PLS). An optimal two-component WA-PLS model provided a high jack-knifed coeffi- cient of prediction for conductivity r 2jack = 0.76, with a low root mean squared error of prediction (RMSEPjack = 0.13). Using this model it is possible to produce long-term quantitative records of past water quality for lacustrine sites across the middle and lower reaches of the Yangtze River, which has important implications for future lake management and eco- logical restoration.

关键词：湖泊亚化石摇蚊推理模型长江中下游地区

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Analyses on the climate change responses over China under SRES B2 scenario using PRECIS

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Chinese Science Bulletin 2006年第18期51卷 2260-2267页

作者： XU Yinlong ZHANG Yong LIN Erda LIN Wantao DONG Wenjie richard jones David Hassell Simon Wilson Institute of Environment and Sustainable Development in Agriculture Chinese Academy of Agricultural Sciences Beijing 100081 China Institute of Atmospheric Physics Chinese Academy of Sciences Beijing 100029 China National Climate Center Beijing 100081 China Met Office Hadley Centre for Climate Prediction and Research Exeter EXI 3PB UK

The PRECIS,a regional climate model system developed at the UK Met Office Hadley Cen- tre for Climate Prediction and Research,which is nested in one-way mode within the HadAM3P,a higher-resolution version of the atmospheric com- ponent of the Hadley Centre climate model HadCM3,is employed to simulate the baseline (1961—1990) climate for evaluation of model’s capacity of simu- lating present climate and analyze the future climate change responses in the time-slice of 2071—2100 (2080s) under SRES B2 scenario over China relative to baseline average. It is indicated from the com- parison of the simulated baseline climate with in situ observation that PRECIS can simulate the local dis- tribution characteristics of surface air temperature over China quite well; generally speaking,the simu- lation for precipitation in the north of China and in winter is better than in the south of China and in summer,respectively; the simulation of precipitation in summer is sensitive to topography,and the simu- lated precipitation values are lower than observations over southeast coastal areas. It is shown from the analyses on the simulated climate change responses in 2080s under SRES B2 scenario relative to base- line that there would be an obvious surface air tem- perature increase in the north of China relative to that in the south of China,and especially in Northwest China and Northeast China,the amplitude ofsummer mean surface air temperature increments could reach 5℃; there would be an overall increase of the simulated precipitation in 2080s under SRES B2 scenario over most areas of China,while there would be significant precipitation decreases in South China in winter; there would be obvious precipitation decreases in Northeast China and North China in summer with high surface air temperature increase. However,it presents an obvious precipitation in- crease over the middle and lower reaches of the Yangtze River in summer.

关键词：地面气温降水 PRECIS 气候变化中国

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Designing Hardware for the Boundary Condition Round Robin Challenge

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Sound & Vibration 2018年第1期52卷 9-12页

作者： David E.Soine richard J.jones Julie M.Harvie Troy J.Skousen Tyler F.Schoenherr Kansas City National Security Campus* 14520 Botts RoadKansas CityMissouriUSA Sandia National Laboratories P.O.Box 5800-MS 0840AlbuquerqueNM 87185

Qualification of products to their vibration and shock requirements in a laboratory setting consists of two basic *** first is the quantification of the product’s mechanical environment in the *** second is the process of testing the product in the laboratory to ensure it is robust enough to survive the field *** latter part is the subject of the“Boundary Condition for Component Qualification”challenge *** paper describes the challenges in determining the appropriate boundary conditions and input stimulus required to qualify the *** paper also describes the step sand analyses that were taken to design a set of hardware that demonstrates the issue and can be used by round robin challenge participants to investigate the problem.

关键词： field. Boundary Robin

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不同硬度楔形鞋垫对膝关节内翻力矩的影响

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医用生物力学 2017年第6期32卷 524-528页

作者：李鸣刘安民汪方 jones richard 王丹上海交通大学附属第一人民医院创伤骨科上海201600 School of Heahh Sciences College of Health and Social CareUniversity of SalfordSalford M5 dWTUK

目的研究不同硬度楔形鞋垫在步行状态下对膝关节内翻力矩的影响。方法 15名健康成年男性受试者穿着不同硬度楔形鞋垫进行步态测试,通过光学运动捕捉系统和地面测力板收集运动学和动力学数据,经Visual3D软件计算得出膝关节内翻力矩,分析... 详细信息

目的研究不同硬度楔形鞋垫在步行状态下对膝关节内翻力矩的影响。方法 15名健康成年男性受试者穿着不同硬度楔形鞋垫进行步态测试,通过光学运动捕捉系统和地面测力板收集运动学和动力学数据,经Visual3D软件计算得出膝关节内翻力矩,分析在3种不同步行状况下(仅穿鞋、鞋中放入软、硬楔形鞋垫)膝关节内翻力矩峰值的差异。结果与较软的楔形鞋垫相比,较硬的楔形鞋垫可使膝关节内翻力矩的第1个峰值降低9.3%,第2个峰值降低9.7%,差异具有统计学意义。结论楔形鞋垫增加一定的硬度能更多降低膝关节内侧间室的压力,减轻关节面的磨损,从而可能缓解膝关节炎症状。

关键词：骨关节炎膝关节内翻力矩硬度楔形鞋垫步态分析

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Using a Game to Engage Stakeholders in Extreme Event Attribution Science

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International Journal of Disaster Risk Science 2016年第4期7卷 353-365页

作者： Hannah R.Parker Rosalind J.Cornforth Pablo Suarez Myles R.Allen Emily Boyd Rachel James richard G.jones Friederike E.L.Otto Peter Walton Department of Meteorology University of Reading Walker Institute University of Reading Red Cross Red Crescent Climate Centre Pardee Center for the Study of the Longer-Range Future Boston University Environmental Change Institute University of Oxford Atmospheric Oceanic and Planetary PhysicsUniversity of Oxford Department of Geography and Environmental Science University of Reading Present Address:Lund University Centre for Sustainability Studies Met Office Hadley Centre School of Geography and the Environment University of Oxford

The impacts of weather and climate-related disasters are increasing,and climate change can exacerbate many *** communicating climate risk and integrating science into policy requires scientists and stakeholders to work *** dialogue between scientists and policymakers can be challenging given the inherently multidimensional nature of the issues at stake when managing climate *** on the growing use of serious games to create dialogue between stakeholders,we present a new game for policymakers called Climate Attribution Under Loss and Damage:Risking,Observing,Negotiating(CAULDRON).CAULDRON aims to communicate understanding of the science attributing extreme events to climate change in a memorable and compelling way,and create space for dialogue around policy decisions addressing changing risks and loss and damage from climate *** describe the process of developing CAULDRON,and draw on observations of players and their feedback to demonstrate its potential to facilitate the interpretation of probabilistic climate information and the understanding of its relevance to informing *** looking to engage with stakeholders can learn valuable lessons in adopting similar innovative *** suitability of games depends on the policy context but,if used appropriately,experiential learning can drive coproduced understanding and meaningful dialogue.

关键词： Climate change Extreme event attribution Loss and damage policy Participatory games Probabilistic event attribution(PEA) Risk management

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利用ECMWF再分析数据验证PRECIS对中国区域气候的模拟能力

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中国农业气象 2004年第1期25卷 5-9页

作者：许吟隆 richard jones 中国农业科学院农业环境与可持续发展研究所北京100081 Met Office Hadley Centrefor Climate Prediction and Research UK

本文利用1979-1983年的ECMWF再分析数据作为准观测侧边界条件驱动:Hadley气候预测和研究中心的区域气候模式系统PRECIS,验证PRECIS对中国区域的气候模拟能力。选择典型的观测站点北京模拟的日最高/最低气温、太阳短波总辐射和月均降水... 详细信息

本文利用1979-1983年的ECMWF再分析数据作为准观测侧边界条件驱动:Hadley气候预测和研究中心的区域气候模式系统PRECIS,验证PRECIS对中国区域的气候模拟能力。选择典型的观测站点北京模拟的日最高/最低气温、太阳短波总辐射和月均降水量与观测结果进行直接比较,显示:PRECIS具有很强的模拟地面气候季节变化的能力。全国740个台站的观测与模拟值的统计分析表明:尽管模拟的最高,最低气温在0℃附近有一‘锯齿’状的偏差,PRECIS能够很好地模拟全国范围最高/最低气温的型态分布特征;从全国范围看,模拟的降水值偏高,但显示出很强的模拟极端降水事件的能力;模拟的地面太阳短波总辐射与全国122个台站的观测结果的比较显示:PRECIS模拟的辐射值偏高,全国范围内约高22％。因此,当应用PRECIS输出结果进行气候变化的影响评价时,需要对模式的输出结果进行订正。

关键词： ECMWF 数据验证 PRECIS 中国区域气候模拟能力

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长江中下游地区典型湖泊摇蚊亚化石-湖水总磷定量模型研究

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科学通报 2006年第11期51卷 1318-1325页

作者：张恩楼 Alan Bedford richard jones 沈吉王苏民唐红渠中国科学院南京地理与湖泊研究所南京210008 Natural Geographical and Applied Sciences Edge Hill College Ormskirk L39 4QPEngland Department of Geography University of Exeter Exeter EX4 4RJEngland 南开大学生命科学学院天津300017

长江中下游地区30个典型湖泊表层摇蚊幼虫亚化石-环境数据库研究表明影响该地区湖泊中摇蚊组合的主导因素为营养态梯度．12个水质环境指标的典型对应分析(CCA)揭示总磷为解释摇蚊幼虫亚化石组合变化的最重要的显著性指标,可解释20．1％... 详细信息

长江中下游地区30个典型湖泊表层摇蚊幼虫亚化石-环境数据库研究表明影响该地区湖泊中摇蚊组合的主导因素为营养态梯度．12个水质环境指标的典型对应分析(CCA)揭示总磷为解释摇蚊幼虫亚化石组合变化的最重要的显著性指标,可解释20．1％的摇蚊幼虫亚化石组合变化信息,适于进行定量模型的建立．依据总磷的DCCA分析,利用非线性的多元回归方法,建立了摇蚊幼虫亚化石-湖水总磷转换函数模型．最佳二次次残差提取的WA-PLS模型为摇蚊幼虫亚化石-总磷转换函数推导提供了最高的实测值与推导值的回归相关系数(R2jack=0．76)和较低的推导误差(RMSEPjack0．13)．最后,对模型的推导能力进行了综合评价．该模型的建立为定量研究该地区湖泊富营养化的历史开拓了新途径,并为湖泊环境管理与生态修复提供了科学依据．

关键词：湖泊摇蚊幼虫亚化石总磷定量转换函数长江中下游

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Non-fullerene acceptor fibrils enable efficient ternary organic solar cells with 16.6% efficiency

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Science China Chemistry 2020年第10期63卷 1461-1468页

作者： Donghui Li Xiaolong Chen Jinglong Cai Wei Li Mengxue Chen Yuchao Mao Baocai Du Joel A.Smith Rachel C.Kilbride Mary E.O'Kane Xue Zhang Yuan Zhuang Pang Wang Hui Wang Dan Liu richard A.L.jones David G.Lidzey Tao Wang School of Materials Science and Engineering Wuhan University of TechnologyWuhan 430070China State Key Laboratory of Silicate Materials for Architectures Wuhan University of TechnologyWuhan 430070China Department of Physics and Astronomy University of SheffieldSheffield.S37RHUK

Optimizing the components and morphology within the photoactive layer of organic solar cells(OSCs)can significantly enhance their power conversion efficiency(PCE).A new A-D-A type non-fullerene acceptor IDMIC-4F is designed and synthesized in this work,and is employed as the third component to prepare high performance ternary solar ***-4F can form fibrils after solution casting,and the presence of this fibrillar structure in the PBDB-T-2F:BTP-4F host confines the growth of donors and acceptors into fine domains,as well as acting as transport channels to enhance electron *** junction ternary devices incorporating 10 wt%IDMIC-4F exhibit enhanced light absorption and balanced carrier mobility,and achieve a maximum PCE of 16.6%compared to 15.7%for the binary device,which is a remarkable efficiency for OSCs reported in *** non-fullerene acceptor fibril network strategy is a promising method to improve the photovoltaic performance of ternary OSCs.

关键词： ternary solar cells non-fullerene acceptor fibrils power conversion efficiency

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