Selection of Response Criteria for Clinical Trials of Sarcoma Treatment

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139995/1/onco0032.pd

Development of dynamic submarine MV power cable design solutions for floating offshore renewable energy applications

This paper reviews approaches to design, modelling and testing of submarine dynamic power cables given the systems requirements for floating offshore renewable energy (ORE). It mainly focuses on the global loading regime and internal mechanical stress estimation in highly dynamic working conditions as well as the assessment of cable mechanical properties, strength and fatigue life

Factors affecting the successful implementation of a digital intervention for health financing in a low-resource setting at scale: semistructured interview study with health care workers and management staff

BACKGROUND: Digital interventions for health financing, if implemented at scale, have the potential to improve health system performance by reducing transaction costs and improving data-driven decision-making. However, many interventions never reach sustainability, and evidence on success factors for scale is scarce. The Insurance Management Information System (IMIS) is a digital intervention for health financing, designed to manage an insurance scheme and already implemented on a national scale in Tanzania. A previous study found that the IMIS claim function was poorly adopted by health care workers (HCWs), questioning its potential to enable strategic purchasing and succeed at scale. OBJECTIVE: This study aimed to understand why the adoption of the IMIS claim function by HCWs remained low in Tanzania and to assess implications for use at scale. METHODS: We conducted 21 semistructured interviews with HCWs and management staff in 4 districts where IMIS was first implemented. We sampled respondents by using a maximum variation strategy. We used the framework method for data analysis, applying a combination of inductive and deductive coding to organize codes in a socioecological model. Finally, we related emerging themes to a framework for digital health interventions for scale. RESULTS: Respondents appreciated IMIS's intrinsic software characteristics and technical factors and acknowledged IMIS as a valuable tool to simplify claim management. Human factors, extrinsic ecosystem, and health care ecosystem were considered as barriers to widespread adoption. CONCLUSIONS: Digital interventions for health financing, such as IMIS, may have the potential for scale if careful consideration is given to the environment in which they are placed. Without a sustainable health financing environment, sufficient infrastructure, and human capacity, they cannot unfold their full potential to improve health financing functions and ultimately contribute to universal health coverage

Taking nature into lab: biomineralization by heavy metal-resistant streptomycetes in soil

Biomineralization by heavy metal-resistant streptomycetes was tested to evaluate the potential influence on metal mobilities in soil. Thus, we designed an experiment adopting conditions from classical laboratory methods to natural conditions prevailing in metal-rich soils with media spiked with heavy metals, soil agar, and nutrientenriched or unamended soil incubated with the bacteria. As a result, all strains were able to form struvite minerals (MgNH4PO4 6H2O) on tryptic soy broth (TSB)-media supplemented with AlCl3, MnCl2 and CuSO4, as well as on soil agar. Some strains additionally formed struvite on nutrient-enriched contaminated and control soil, as well as on metal contaminated soil without addition of media components. In contrast, switzerite (Mn3(PO4)2 7H2O) was exclusively formed on minimal media spiked with MnCl2 by four heavy metal-resistant strains, and on nutrient-enriched control soil by one strain. Hydrated nickel hydrogen phosphate was only crystallized on complex media supplemented with NiSO4 by most strains. Thus, mineralization is a dominant property of streptomycetes, with different processes likely to occur under laboratory conditions and sub-natural to natural conditions. This new understanding might have implications for our understanding of biological metal resistance mechanisms. We assume that biogeochemical cycles, nutrient storage and metal resistance might be affected by formation and re-solubilization of minerals like struvite in soil at microscale

Phase II Study of Sequential Gemcitabine Followed by Docetaxel for Recurrent Ewing Sarcoma, Osteosarcoma, or Unresectable or Locally Recurrent Chondrosarcoma: Results of Sarcoma Alliance for Research Through Collaboration Study 003

Background.Gemcitabine and docetaxel have a broad spectrum of clinical activity in patients with carcinoma. The Sarcoma Alliance for Research Through Collaboration conducted a phase II trial of gemcitabine in combination with docetaxel in children and adults with recurrent Ewing sarcoma (EWS), osteosarcoma (OS), or unresectable or recurrent chondrosarcoma. The primary objective was to determine the objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST).Methods.Gemcitabine (675 mg/m2 i.v. over 90 minutes on days 1 and 8) was administered in combination with docetaxel (75 mg/m2 i.v. over 1 hour on day 8) every 21 days. All patients received filgrastim or pegfilgrastim. A Bayesian formulation was used to determine the probability of achieving the target response rate for each subtype—0.35 for EWS and OS or 0.20 for chondrosarcoma. If the probability of achieving the target response rate was <0.05, the combination was considered inactive. Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.Results.Fifty‐three eligible patients were enrolled in the three subtype groups—OS (n = 14), EWS (n = 14), and chondrosarcoma (n = 25). Toxicities included neutropenia, thrombocytopenia, fatigue, dyspnea, bronchospasm, edema, neuropathy, and liver function abnormalities. Dose modification for toxicity was required for eight patients during cycle 1 and 16 patients in subsequent cycles. Seven patients withdrew from therapy as a result of toxicity. No complete responses were observed. Partial responses were observed in OS (n = 1), EWS (n = 2), and chondrosarcoma (n = 2) patients.Conclusion.Gemcitabine in combination with docetaxel was associated with a probability of reaching the target 35% response rate of <5% in OS patients and 5.6% in EWS patients; the probability of reaching a 20% response rate in chondrosarcoma patients was 14%.摘要背景. 吉西他滨与多西他赛对癌症患者有广谱的临床疗效。 肉瘤研究联盟协作组在复发的尤文肉瘤 （EWS）、 骨肉瘤 （OS）、 不可切除或复发的软骨肉瘤成人和儿童患者中开展了吉西他滨联合多西他赛的 II 期试验。 主要目的为通过实体瘤疗效评估标准 （RECIST） 确定客观缓解率。方法. 吉西他滨 （675 mg/m2， 静脉滴注 90 分钟以上， 第 1 和 8 天） 联合多西他赛 （75 mg/m2， 静脉滴注 1 小时以上， 第 8 天） 每 21 天给药 1 次。 全部患者均同时接受非格司亭或乙二醇化非格司亭。 利用贝叶斯公式来确定各个亚型达到目标缓解率的概率——EWS 和 OS 为 0.35， 软骨肉瘤为 0.20。 如果达到目标缓解率的概率 < 0.05， 则认为联合方案无效。 毒性反应根据不良事件通用术语标准 （CTCAE） 3.0 版来分级。结果. 53 例合格患者入组 3 个亚型组 ： OS （n=14）、 EWS （n=14）、 软骨肉瘤 （n=25）。 毒性反应包括中性粒细胞减少、 血小板减少、 乏力、 呼吸困难、 支气管痉挛、 水肿、 神经病变以及肝功能异常。 第 1 个周期有 8 例患者、 其后周期有 16 例患者因毒性反应而需要剂量调整。 7 例患者因毒性反应而撤出治疗。 未观察到完全缓解。 OS （n=1）、 EWS （n=2） 和软骨肉瘤 （n=2） 组均有患者达到部分缓解。结论. 吉西他滨联合多西他赛在 < 5% 的 OS 患者、 5.6% 的 EWS 患者中达到目标缓解率的概率为 35%； 14% 软骨肉瘤患者中达到目标缓解率的概率为 20%。讨论. 贝叶斯公式能够评估各个亚型在分别进行缓解率评估后预测达到目标缓解率的概率。 通过多角度来看这些数据， 在考量达到目标缓解率的概率以及入组率之后即能发现本研究设计方案阻碍了研究的继续开展。 因为这一设计方案并未设定判断治疗为 “有效” 的规则， 所以并不适合与标准的分 2 阶段进行的 II 期试验设计直接比较。 关闭 EWS 和软骨肉瘤亚组的决定， 某种程度上是基于入组缓慢， 另外达到目标缓解率的概率较低也支持这一决定。 入组率而不是统计设计， 对试验周期有显著影响。The Oncologist 2012;17:321‐e329Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/1/onco0321-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/2/onco0321-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/3/onco0321.pd

Universities and community-based research in developing countries: community voice and educational provision in rural Tanzania

The main focus of recent research on the community engagement role of universities has been in developed countries, generally in towns and cities and usually conducted from the perspectives of universities rather than the communities with which they engage. The purpose of this paper is to investigate the community engagement role of universities in the rural areas of developing countries, and its potential for strengthening the voice of rural communities. The particular focus is on the provision of primary and secondary education. The paper is based on the assumption that in order for community members to have both the capacity and the confidence to engage in political discourse for improving educational capacity and quality, they need the opportunity to become involved and well-versed in the options available, beyond their own experience. Particular attention is given in the paper to community-based research (CBR). CBR is explored from the perspectives of community members and local leaders in the government-community partnerships which have responsibility for the provision of primary and secondary education in rural Tanzania. The historical and policy background of the partnerships, together with findings from two case studies, provide the context for the paper

Nurturing lifelong learning in communities through the National University of Lesotho: prospects and challenges

This paper analyses one aspect of a pan-African action research project called ITMUA (Implementing the Third Mission of Universities in Africa). This particular paper draws on the data from that project to explore the National University of Lesotho’s contribution to lifelong learning in its communities. It provides background information on the ITMUA initiative and analyses interview and focus group responses to two case studies in terms of their contribution to lifelong learning. It uses, as its analytical framework, a modified version of Mbigi’s African perspective on the four De Lors’ ‘pillars’, by adding a fifth pillar, courtesy of Torres. The paper argues that community engagement is a two-way process between universities and their wider constituencies with opportunities for mutual lifelong learning. But there are also challenges of understanding and process which must be addressed if the full range of these lifelong learning pillars is to be accommodated within African contexts. The paper provides an introduction to the history of community engagement in Africa as a university mission, followed by a brief discussion of lifelong learning within African perspectives. After describing the particular context of Lesotho, the concept of community service and community engagement in contemporary African contexts introduces the action research project and the case studies. The final part of the paper presents and discusses the research findings