BACKGROUND & AIMS: This paper presents and discusses selected findings from a study of health-seeking strategies in relation to sexual health among a group of female sex workers in Calcutta, India. Background information on sex work and sexually transmitted disease in Calcutta is followed by the presentation of findings pertaining to women's understandings of (sexual) health, treatment-seeking and service utilisation. In the urban context where health services are readily available, patterns of initial treatment-seeking are shown to be generally (biomedically) appropriate, but subsequent "non-compliant" therapeutic practices give cause for concern. Conventional approaches to the study of "health-seeking behaviour" are reviewed in the light of these findings and questions raised about the appropriateness of approaches that focus on initial choice of treatment type and/or assume processes of health-seeking to be determined primarily by cultural "beliefs" about illness. Inherent biomedical and culturalist biases in the orientation of such research are shown to produce an analytic neglect of the dual influences of material life conditions and people's perceptions of health, rather than illness, upon health-related strategies. Recommendations are made for operational research and policy formulation on the provision of effective sexual health services, and implications are drawn for the scope of interventions and applied research directed at improving sexual health.

背景与目标： 本文介绍并讨论了印度加尔各答一群女性性工作者与性健康有关的寻求健康策略研究的部分发现。关于加尔各答性工作和性传播疾病的背景信息之后，介绍了与妇女对 (性) 健康，寻求治疗和服务利用的理解有关的发现。在容易获得医疗服务的城市环境中，最初寻求治疗的方式通常 (在生物医学上) 是适当的，但是随后的 “不合规” 治疗方法引起了人们的关注。根据这些发现和提出的有关方法的适当性的问题，对 “寻求健康行为” 研究的常规方法进行了审查，这些方法侧重于治疗类型的初始选择和/或假设寻求健康的过程主要由关于疾病的文化 “信仰” 决定。这种研究方向上固有的生物医学和文化主义偏见被证明是对物质生活条件和人们对健康而不是疾病的看法对健康相关策略的双重影响的分析忽略。提出了有关提供有效性健康服务的业务研究和政策制定的建议，并对旨在改善性健康的干预措施和应用研究的范围提出了影响。

BACKGROUND & AIMS: :Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, there is evidence that abnormalities in specific brain structures and their interconnections confer vulnerability to the development of late-life depression. Structural magnetic resonance imaging methods can be used to identify and quantify brain abnormalities predisposing to geriatric depression and in prediction of treatment response. This article reviews several techniques, including morphometric approaches, study of white matter hyperintensities, diffusion tensor imaging, magnetization transfer imaging, t2 relaxography, and spectroscopy, that have been used to examine these brain abnormalities with a focus on the type of information obtained by each method as well as each method's limitations. The authors argue that the available methods provide complementary information and that, when combined judiciously, can increase the knowledge gained from neuroimaging findings and conceptually advance the field of geriatric depression.

背景与目标： : 老年抑郁症由复杂和异质的行为组成，不太可能由单个脑部病变引起。然而，有证据表明，特定大脑结构及其相互联系的异常使人们容易患上晚期抑郁症。结构磁共振成像方法可用于识别和量化易患老年抑郁症的脑部异常，并预测治疗反应。本文回顾了几种技术，包括形态计量学方法，白质高强度研究，扩散张量成像，磁化转移成像，t2弛豫成像和光谱学，这些技术已用于检查这些大脑异常，重点是获得的信息类型通过每种方法以及每种方法的局限性。作者认为，可用的方法提供了补充信息，并且如果明智地结合在一起，可以增加从神经影像学发现中获得的知识，并在概念上推进老年抑郁症领域。

BACKGROUND & AIMS: INTRODUCTION:Ethics committees are a necessary resource to guarantee ethical integrity in human research; they must apply international standards in their ethical evaluation of research projects involving human subjects. OBJECTIVE:The ethics committees for human research of Colombia were characterized, and recommendations for strengthening them were formulated. MATERIALS AND METHODS:In 2003, 280 groups with research projects involving human subjects were selected from a list of research groups which form part of the science and technology network of Colciencias. (Colciencias is the Colombian national agency that promotes and funds science and technology.) Eighty percent (224) of the projects were associated with 40 institutions, consisting of universities, hospitals, and public or private research centers. Thirty of these institutions had at least one ethics committee for evaluating use of human subjects. A questionnaire was mailed to each of these Committees, requesting information concerning its their compostition, regulations, multidisciplinarity, plurality, representativity and independence. The World Health Organization's Operational Guidelines for Ethic Committees that Evaluate Biomedical Research (TDR/PRD/ETHICS/2000) was used as reference for the analysis. In 5 of the cities, supplemental information was obtained by direct discussions with members of the ethics committees. RESULTS:Twenty-six committees responded to the questionnaire. The results indicated that 47% of the committee members were physicians, but only 23% of the committees had representatives from the community. In 60% of the Committees, members were not independent from the organization in which it was based. Seventy percent had established operating procedures. Lack of national regulations and limited education in research ethics were mentioned as the main drawbacks in providing effective guidance. CONCLUSIONS:These observations led to the conclusion that national guidelines must be established for ethics committees that correspond to international standards. Committee members must be trained before accepting committee responsibilities. Finally, new committees must be created along with the improvement of the currently existing committees for reinforcing and promoting the importance of ethical integrity in research.

背景与目标：

BACKGROUND & AIMS: :The mode of action of Vibrio vulnificus haemolysin (VVH) on mast cells from the peritoneal cavity of the rat was examined. VVH induced histamine release, and damage to the mast cells, in a dose-dependent fashion. When 1 microgram of VVH was added to c. 10(5) mast cells at 37 degrees C, histamine release was observed after a lag period of 5-10 s, and was complete within 5 min. The action was temperature-dependent, and was not induced at 4 degrees C. Disodium cromoglycate, a membrane stabiliser for mast cells, inhibited the histamine release significantly, but the effect was not dose-dependent. Moreover, leakage of lactate dehydrogenase from VVH-treated mast cells was observed. These results suggest that VVH acts on the cell membrane of mast cells and is cytolytic.

背景与目标： : 检查了创伤弧菌溶血素 (VVH) 对大鼠腹膜腔肥大细胞的作用方式。VVH以剂量依赖性方式诱导组胺释放并损害肥大细胞。当在37 ℃ 下将1微克VVH加入c. 10(5) 肥大细胞时，在5-10 s的滞后期后观察到组胺释放，并在5分钟内完成。该作用与温度有关，在4 ℃ 下未诱导。色甘氨酸二钠是肥大细胞的膜稳定剂，可显着抑制组胺的释放，但其作用不是剂量依赖性的。此外，观察到乳酸脱氢酶从VVH处理的肥大细胞中泄漏。这些结果表明，VVH作用于肥大细胞的细胞膜并具有溶细胞性。

BACKGROUND & AIMS: BACKGROUND:Telephone surveys have been used widely in public health research internationally and are being increasingly used in Ireland and the U.K. METHODS:This study compared three telephone surveys conducted on the island of Ireland from 2000 to 2004, examining study methodology, outcome measures and the per unit cost of each completed survey. We critically examined these population-based surveys which all explored health related attitudes and behaviours. RESULTS:Over the period from 2000 to 2005 the percentage of calls which succeeded in contacting an eligible member of the public fell, from 52.9% to 31.8%. There was a drop in response rates to the surveys (once contact was established) from 58.6% to 17.7%. Costs per completed interview rose from 4.48 euro to 15.65 euro. Respondents were prepared to spend 10-15 minutes being surveyed, but longer surveys yielded poorer completion rates. Respondents were willing to discuss issues of a sensitive nature. Interviews after 9 pm were less successful, with complaints about the lateness of the call. Randomisation from electronic residential telephone directory databases excluded all ex-directory numbers and thus was not as representative of the general population as number generation by the hundred-bank method. However the directory database was more efficient in excluding business and fax numbers. CONCLUSION:Researchers should take cognisance of under-representativeness of land-line telephone surveys, of the increasing difficulties in contacting the public and of mounting personnel costs. We conclude that telephone surveying now requires additional strategies such as a multimode approach, or incentivisation, to be a useful, cost-effective means of acquiring data on public health matters in Ireland and the U.K.

背景与目标：

BACKGROUND & AIMS: :The biological actions of the insulin-like growth factors, IGF-I and IGF-II, are mediated by the ligand-induced activation of the IGF-I receptor (IGF-IR), a transmembrane heterotetramer linked to the ras-raf-mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3 kinase (PI3K)-protein kinase B (PKB)/Akt signal transduction cascades. The Wilms' tumor suppressor gene (wt1) encodes a zinc finger transcription factor, WT1, which has been implicated in various cellular processes including proliferation, differentiation and apoptosis. In the present study we demonstrated that IGF-I modulates the WT1 gene expression in neurally derived PC12 cells in a dose- and time-dependent manner. This effect was mediated through both the MAPK and PI3-kinase signaling pathways, as shown by the ability of the specific inhibitors UO126 and LY294002 to abrogate IGF-I action. Moreover, using RT-PCR and transient transfection assays, we demonstrated that the IGF-I effect was associated with corresponding changes in WT1 mRNA levels and WT1 promoter activity. In addition, the results of the present study revealed that high WT1 levels were associated with the induction of apoptosis, whereas low WT1 levels were correlated with the inhibition of apoptosis, as demonstrated by poly ADP ribose polymerase (PARP) cleavage, Bax expression, Annexin V-FITC staining, and by the use of antisense oligonucleotides against WT1. In summary, our results show that the wt1 gene is a novel target for IGF-I action in neurally derived cells.

背景与目标： : 胰岛素样生长因子igf-i和igf-ii的生物学作用是由配体诱导的igf-i受体 (igf-ir) 激活介导的，与ras-raf-有丝分裂原活化蛋白激酶 (MAPK) 和磷脂酰肌醇3激酶 (PI3K)-蛋白激酶B (PKB)/Akt信号转导级联连接的跨膜异四聚体。Wilmss的肿瘤抑制基因 (wt1) 编码锌指转录因子WT1，该因子与各种细胞过程有关，包括增殖，分化和凋亡。在本研究中，我们证明igf-i以剂量和时间依赖性方式调节神经源性PC12细胞中WT1基因的表达。这种作用通过MAPK和PI3-kinase信号通路介导，如特异性抑制剂UO126和LY294002消除igf-i作用的能力所示。此外，使用rt-pcr和瞬时转染分析，我们证明了igf-i效应与WT1 mRNA水平和WT1启动子活性的相应变化有关。此外，本研究的结果表明，高WT1水平与诱导凋亡有关，而低WT1水平与抑制凋亡有关，如聚ADP核糖聚合酶 (PARP) 切割，Bax表达，Annexin V-FITC染色，并通过使用针对wt1的反义寡核苷酸。总之，我们的结果表明wt1基因是神经源性细胞中igf-i作用的新靶标。

BACKGROUND & AIMS: :Insulin resistance affecting skeletal muscle metabolism is present in the prehypertensive state. The aim of our study was to test the hypothesis that blood pressure value is related to skeletal muscle composition, measured by (31)P magnetic resonance (MR) spectroscopy, and to insulin sensitivity in the offspring of hypertensive parents (OH) and healthy controls. Study groups consisted of 10 healthy young lean OH with normal glucose tolerance, confirmed with oral glucose tolerance test, and 13 controls matched for age, sex, and body mass index. Insulin action was estimated as glucose disposal (M), glucose metabolic clearance rate (MCR), and insulin sensitivity index (M/I) during a 10-hour hyperinsulinemic euglycemic clamp. The sum of immunoreactive insulin values from the oral glucose tolerance test was calculated. (31)P MR spectroscopy was performed on a whole-body MR scanner (Siemens Vision, Erlangen, Germany) operating at 1.5 T and equipped with actively shielded gradient coils. There were no differences in common metabolic and anthropometric parameters between OH and controls except for the blood pressure, which was in the range of normal to high-normal level in OH. Mean blood pressure was significantly higher in OH (95.73 +/- 4.39 vs 83.76 +/- 3.95 mm Hg; P < .001). Trend toward insulin resistance was registered in OH with significantly lower M/I (0.74 +/- 0.47 vs 1.42 +/- 0.65 mg x kg(-1) x min(-1) x mIU(-1) x L(-1); P < .05). There were no significant differences in total serum magnesium (sMg) levels between OH and controls, although a positive correlation exists between sMg and insulin sensitivity expressed as M (r = 0.63, P < .01), MCR (r = 0.54, P < .01), and M/I (r = 0.51, P < .05). No differences in signal intensities of phosphocreatine (PCr), phosphomonoesters, phosphodiesters, inorganic phosphates (Pi), adenosine triphosphates (Patp and betaATP), and calculated concentrations of intracellular ionized magnesium (Mgi) and H(+) ions between the groups were detected. Systolic blood pressure correlates positively with PCr/Patp (r = 0.43, P < .05), Pi/Patp (r = 0.413, P < .05), and Pi/betaATP (r = 0.48, P < .05). Diastolic blood pressure correlates positively only with the ratio Pi/betaATP (r = 0.42, P < .05). The sum of immunoreactive insulin values correlates with PCr/betaATP (r = 0.53, P < .01) and with Pi/betaATP (r = 0.6, P < .01). In conclusion, increase in blood pressure and insulin resistance were confirmed in offspring of OH. Insulin sensitivity is related to sMg and the elevation of blood pressure is associated with the activation of energy metabolism in skeletal muscle. The relationship between muscle energetic characteristics and markers of insulin resistance suggests that the alteration of energy metabolism may be present in early stages of metabolic syndrome.

背景与目标： : 影响骨骼肌代谢的胰岛素抵抗在高血压前期存在。我们研究的目的是检验以下假设: 血压值与通过 (31)P磁共振 (MR) 光谱法测量的骨骼肌组成以及高血压父母 (OH) 和健康的后代的胰岛素敏感性有关对照。研究组由10个健康的年轻lean OH组成，葡萄糖耐量正常，经口服葡萄糖耐量试验证实，以及13个年龄，性别和体重指数相匹配的对照。在10小时的高胰岛素血症正常血糖钳夹中，胰岛素的作用估计为葡萄糖处置 (M)，葡萄糖代谢清除率 (MCR) 和胰岛素敏感性指数 (M/I)。计算了口服葡萄糖耐量试验的免疫反应性胰岛素值之和。(31) 在操作于1.5 T并配备有主动屏蔽梯度线圈的全身MR扫描仪 (Siemens Vision，Erlangen，德国) 上进行P MR光谱。OH和对照组之间的常见代谢和人体测量参数没有差异，但血压在OH的正常至正常水平范围内。OH中的平均血压显着更高 (95.73/- 4.39 vs 83.76/-3.95毫米Hg; P <.001)。在OH中记录了胰岛素抵抗的趋势，M/I显著降低 (0.74 +/- 0.47 vs 1.42 +/- 0.65 mg × kg(-1) × min(-1) × mIU(-1) × L(-1); P <.05)。血清总镁 (sMg) 水平与对照组无显著差异，但sMg与胰岛素敏感性呈正相关，表现为M (r = 0.63，P <.01)，MCR (r = 0.54，P <.01)。和M/I (r = 0.51，P <.05)。检测到磷酸肌酸 (PCr)，磷酸单酯，磷酸二酯，无机磷酸盐 (Pi)，三磷酸腺苷 (Patp和 βatp) 的信号强度以及计算的细胞内离子镁 (Mgi) 和H () 离子浓度之间的差异。收缩压与PCr/Patp (r = 0.43，P <.05) 、Pi/Patp (r = 0.413，P <.05) 和Pi/betaATP (r = 0.48，P <.05) 呈正相关。舒张压仅与Pi/βatp比值正相关 (r = 0.42，P <.05)。免疫反应性胰岛素值的总和与PCr/betaATP (r = 0.53，P <.01) 和Pi/betaATP (r = 0.6，P <.01) 相关。总之，在OH的后代中证实了血压升高和胰岛素抵抗。胰岛素敏感性与sMg有关，血压升高与骨骼肌能量代谢的激活有关。肌肉能量特征与胰岛素抵抗标志物之间的关系表明，能量代谢的改变可能存在于代谢综合征的早期阶段。

BACKGROUND & AIMS: :Hemorrhage is the most preventable cause of posttraumatic death. Many cases are potentially anatomically salvageable, yet remain lethal without logistics or trained personnel to deliver diagnosis or resuscitative surgery in austere environments. Revolutions in technology for remote mentoring of ultrasound and surgery may enhance capabilities to utilize the skill sets of non-physicians. Thus, our research collaborative explored remote mentoring to empower non-physicians to address junctional and torso hemorrhage control in austere environments. Major studies involved using remote-telementored ultrasound (RTMUS) to identify torso and junctional exsanguination, remotely mentoring resuscitative surgery for torso hemorrhage control, understanding and mitigating physiological stress during such tasks, and the technical practicalities of conducting damage control surgery (DCS) in austere environments. Iterative projects involved randomized guiding of firefighters to identify torso (RCT) and junctional (pilot) hemorrhage using RTMUS, randomized remote mentoring of MedTechs conducting resuscitative surgery for torso exsanguination in an anatomically realistic surgical trainer ("Cut Suit") including physiological monitoring, and trained surgeons conducting a comparative randomized study for torso hemorrhage control in normal (1g) versus weightlessness (0g). This work demonstrated that firefighters could be remotely mentored to perform just-in-time torso RTMUS on a simulator. Both firefighters and mentors were confident in their abilities, the ultrasounds being 97% accurate. An ultrasound-naive firefighter in Memphis could also be remotely mentored from Hawaii to identify and subsequently tamponade an arterial junctional hemorrhage using RTMUS in a live tissue model. Thereafter, both mentored and unmentored MedTechs and trained surgeons completed resuscitative surgery for hemorrhage control on the Cut-Suit, demonstrating practicality for all involved. While remote mentoring did not decrease blood loss among MedTechs, it increased procedural confidence and decreased physiologic stress. Therefore, remote mentoring may increase the feasibility of non-physicians conducting a psychologically daunting task. Finally, DCS in weightlessness was feasible without fundamental differences from 1g. Overall, the collective evidence suggests that remote mentoring supports diagnosis, noninvasive therapy, and ultimately resuscitative surgery to potentially rescue those exsanguinating in austere environments and should be more rigorously studied.

背景与目标： : 出血是创伤后死亡最可预防的原因。许多病例在解剖学上可能是可挽救的，但如果没有后勤人员或训练有素的人员在严峻的环境中进行诊断或复苏手术，则仍然致命。超声波和外科手术远程指导技术的革命可能会增强利用非医生技能的能力。因此，我们的研究合作探索了远程指导，以使非医生能够在严峻的环境中解决交界处和躯干出血控制问题。主要研究包括使用远程远程超声 (RTMUS) 识别躯干和交界性放血，远程指导复苏手术以控制躯干出血，理解和减轻此类任务期间的生理压力，以及在严峻环境中进行损伤控制手术 (DCS) 的技术实用性。迭代项目包括随机指导消防员使用RTMUS识别躯干 (RCT) 和交界 (pilot) 出血，随机远程指导MedTechs在解剖学上逼真的外科训练器 (“切割服”) 中进行躯干放血的复苏手术，包括生理监测，和训练有素的外科医生进行了一项比较随机研究，以正常 (1g) 与失重 (0g) 的躯干出血控制。这项工作表明，可以远程指导消防员在模拟器上执行及时的躯干RTMUS。消防员和导师都对自己的能力充满信心，超声波97% 准确。孟菲斯的一名未经超声检查的消防员也可以从夏威夷进行远程指导，以识别并随后在活组织模型中使用RTMUS填塞动脉交界性出血。此后，经过指导和未经指导的MedTechs和训练有素的外科医生都完成了复苏手术，以控制剪裁服上的出血，这证明了所有参与者的实用性。虽然远程指导并没有减少MedTechs的失血，但它增加了程序信心并减少了生理压力。因此，远程指导可能会增加非医生执行心理艰巨任务的可行性。最后，失重的dc是可行的，与1g没有根本差异。总体而言，集体证据表明，远程指导支持诊断，无创治疗以及最终的复苏手术，以潜在地挽救那些在严峻环境中失血的人，因此应进行更严格的研究。

BACKGROUND & AIMS: BACKGROUND:In 2013, the Declaration of Helsinki changed to mandate that all research studies involving human subjects, rather than just clinical trials alone, must have a protocol registered in a publicly accessible database prior to the enrolment of the first patient. The objective of this work was to assess the number of research studies involving human participants published in leading journals of plastic surgery that had either published a protocol or registered a protocol with a publicly accessible database. MATERIALS AND METHODS:This systematic review examined all research articles involving human participants published in Plastic and Reconstructive Surgery, The Journal of Plastic Reconstructive and Aesthetic Surgery and The Annals of Plastic Surgery from 1st April 2014-31st March 2015. The primary outcome measure was whether each study had either published or registered a protocol with any mainstream registry database. ClinicalTrials.gov, the International Standard Randomized Control Trial Number (ISRCTN) registry, the WHO (World Health Organisation) International Clinical Trials Registry Platform, The Cochrane Collaboration, the Research Registry, PROSPERO and PubMed were all reviewed. RESULTS:Of 595 included articles, the most common study designs were case series (n = 185, 31.1%). There were 24 randomized controlled trials (RCTs, 4.0%). A total of 24 studies had a protocol registered (4.0%). The most common database to register a protocol was with ClinicalTrials.gov (n = 17). The study design that most commonly had a registered protocol was the RCT (n = 8 of 24, 33.3% of RCTs). Three studies published a protocol in a journal (0.6%). CONCLUSION:Publication or registration of protocols for recent studies involving human participants in major plastic surgery journals is low. There is considerable scope to improve this and guidance is provided.

背景与目标：

BACKGROUND & AIMS: :Size perception is known to influence our usual interactions with environment. Numerous studies highlighted that during the visual presentation of an object, the properties of manual actions vary as a function of this object's size. In order to better understand the dynamic variations of relationships between size perception and action, we used an experimental paradigm consisting in two phases. During a previous implicit learning phase, a manual response (right or left) was specifically associated with the appearance of a large or small stimulus. During further test phase, participants were required to prepare a response while discriminating the color of a stimulus (GO/No GO task). We observed that the response execution was faster when the size of the stimulus was congruent with the size that had been associated to this response (during implicit learning phase). These results suggest that when a response usually co-occurs with visual stimuli characterized by a specific size pattern, the response and the size pattern become integrated. Any subsequent preparation and execution of this action are therefore influenced by the reactivation of this visual pattern. This result brings out new insights on how sensorimotor interactions may modulate the ability to anticipate perceptive size variations in the environment.

背景与目标： : 众所周知，大小感知会影响我们通常与环境的互动。大量研究强调，在对象的视觉呈现过程中，手动动作的属性随对象大小的变化而变化。为了更好地理解大小感知和动作之间关系的动态变化，我们使用了一个由两个阶段组成的实验范例。在先前的内隐学习阶段，手动响应 (右或左) 与大或小刺激的出现特别相关。在进一步的测试阶段，要求参与者在区分刺激颜色的同时准备响应 (GO/No GO任务)。我们观察到，当刺激的大小与与该响应相关的大小一致时 (在隐式学习阶段)，响应执行更快。这些结果表明，当响应通常与以特定大小模式为特征的视觉刺激同时发生时，响应和大小模式将成为一体。因此，此操作的任何后续准备和执行都受到此视觉模式重新激活的影响。该结果为感觉运动相互作用如何调节预测环境中感知大小变化的能力带来了新的见解。

BACKGROUND & AIMS: :Stakeholder engagement is an emerging field with little evidence to inform best practices. Guidelines are needed to improve the quality of research on stakeholder engagement through more intentional planning, evaluation and reporting. We developed a preliminary framework for planning, evaluating and reporting stakeholder engagement, informed by published conceptual models and recommendations and then refined through our own stakeholder engagement experience. Our proposed exploratory framework highlights contexts and processes to be addressed in planning stakeholder engagement, and potential immediate, intermediate and long-term outcomes that warrant evaluation. We use this framework to illustrate both the minimum information needed for reporting stakeholder-engaged research and the comprehensive detail needed for reporting research on stakeholder engagement.

背景与目标： : 利益相关者参与是一个新兴领域，几乎没有证据为最佳实践提供信息。需要通过更有意的计划，评估和报告来提高有关利益相关者参与的研究质量的准则。我们通过已发布的概念模型和建议为规划，评估和报告利益相关者参与制定了初步框架，然后通过我们自己的利益相关者参与经验进行了完善。我们提出的探索性框架强调了在规划利益相关者参与时要解决的背景和过程，以及需要评估的潜在的近期，中期和长期结果。我们使用此框架来说明报告利益相关者参与研究所需的最低信息，以及报告利益相关者参与研究所需的全面细节。

BACKGROUND & AIMS: OBJECTIVES:Monochorionic (MC) twins are at increased risk of early fetal loss secondary to vascular complications such as twin-twin transfusion syndrome (TTTS). This study compared the early perinatal loss rates between MC and dichorionic (DC) twins in an era of invasive treatment for TTTS. METHODS:This was a retrospective study of all twin pregnancies of known chorionicity from a large regional cohort of nine hospitals over a 10-year period. Ultrasound data were matched to hospital delivery records and to a mandatory national register of pregnancy losses. Prospective risk of pregnancy loss from 14 to 24 weeks' gestation was calculated and the survival trend of MC and DC twins was analyzed using Kaplan-Meier survival analysis. RESULTS:The analysis included 3117 twin pregnancies (605 MC and 2512 DC). The total risk of early pregnancy loss (miscarriage and neonatal death) before 24 weeks was significantly higher in MC twins (60.3 per 1000 fetuses) than in DC twins (6.6 per 1000 fetuses), with a relative risk of 9.18 (95% CI, 6.0-13.9). Survival analysis showed a significant difference in overall and early mortality between MC and DC twins (log-rank test, P < 0.0001), while no difference was noted after 24 weeks' gestation (log-rank test, P = 0.08). CONCLUSIONS:Early pregnancy loss is significantly more common in MC than in DC twins, but no difference in the prospective risk of mortality between MC and DC twins is evident after 24 weeks' gestation. The observed early mortality rate has almost halved in comparison with previous studies in the published literature. Early detection and prompt treatment of complications in MC twins are likely to have contributed to this improvement in outcome.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Medication used to treat multiple sclerosis (MS) can be categorized as disease-modifying therapies, symptomatic therapies, or treatment of acute exacerbations. Dalfampridine is the first symptomatic therapy approved by the Food and Drug Administration to improve walking in patients with MS. OBJECTIVE:This article reviews the pharmacology, pharmacodynamic properties, and pharmacokinetic properties of dalfampridine, as well as its clinical efficacy, safety profile, pharmacoeconomic considerations, and place in therapy. METHODS:Three PubMed searches were conducted for original articles published in English between 1966 and August 2012 with human study participants. Articles concerning the pharmacology, pharmacokinetic properties, pharmacodynamic properties, efficacy, and safety profile of dalfampridine were evaluated. RESULTS:Dalfampridine theoretically works to improve conduction and enhance walking by inhibiting potassium channels in the axonal membrane and by prolonging action potentials in demyelinated neurons. The efficacy of dalfampridine has been reported in 2 Phase III clinical trials in patients with MS. When comparing dalfampridine 10 mg twice daily with placebo, these studies found a statistically significant improvement in walking (42.9% vs 9.3% and 35% vs 8%; P < 0.001). However, clinical trials and postmarketing surveillance have shown an increased risk of seizures with dalfampridine use that appears to be dose related [corrected]. CONCLUSIONS:Dalfampridine has a unique mechanism of action, leading to its approval as the first symptomatic therapy for MS to improve walking speed. The increased risk of seizures can be a safety concern and will require health care providers to be diligent in monitoring patients and to ensure adequate patient education [corrected]. The addition of dalfampridine as symptomatic therapy for MS may lead to additional novel products in the future.

背景与目标：

BACKGROUND & AIMS: INTRODUCTION:Databases are useful tools in clinical settings. The authors review the benefits and challenges associated with the development and implementation of an efficient electronic database for the multidisciplinary Vascular Birthmark Clinic at the Alberta Children's Hospital, Calgary, Alberta. METHODS:The content and structure of the database were designed using the technical expertise of a data analyst from the Calgary Health Region. Relevant clinical and demographic data fields were included with the goal of documenting ongoing care of individual patients, and facilitating future epidemiological studies of this patient population. After completion of this database, 10 challenges encountered during development were retrospectively identified. Practical solutions for these challenges are presented. RESULTS:THE CHALLENGES IDENTIFIED DURING THE DATABASE DEVELOPMENT PROCESS INCLUDED: identification of relevant data fields; balancing simplicity and user-friendliness with complexity and comprehensive data storage; database expertise versus clinical expertise; software platform selection; linkage of data from the previous spreadsheet to a new data management system; ethics approval for the development of the database and its utilization for research studies; ensuring privacy and limited access to the database; integration of digital photographs into the database; adoption of the database by support staff in the clinic; and maintaining up-to-date entries in the database. CONCLUSIONS:There are several challenges involved in the development of a useful and efficient clinical database. Awareness of these potential obstacles, in advance, may simplify the development of clinical databases by others in various surgical settings.

背景与目标：

BACKGROUND & AIMS: :While human genetic research promises to deliver a range of health benefits to the population, genetic research that takes place in Indigenous communities has proven controversial. Indigenous peoples have raised concerns, including a lack of benefit to their communities, a diversion of attention and resources from non-genetic causes of health disparities and racism in health care, a reinforcement of "victim-blaming" approaches to health inequalities, and possible misuse of blood and tissue samples. Drawing on the international literature, this article reviews the ethical issues relevant to genetic research in Indigenous populations and considers how some of these have been negotiated in a genomic research project currently under way in a remote Aboriginal community. We consider how the different levels of Indigenous research governance operating in Australia impacted on the research project and discuss whether specific guidelines for the conduct of genetic research in Aboriginal and Torres Strait Islander communities are warranted.

背景与目标： : 虽然人类基因研究有望为人们带来一系列健康益处，但事实证明，在土著社区进行的基因研究存在争议。土著人民提出了关切，包括缺乏对其社区的利益，将注意力和资源从健康差异的非遗传原因和卫生保健中的种族主义转移，加强对健康不平等的 “指责受害者” 方法，以及可能滥用血液和组织样本。本文借鉴国际文献，回顾了与土著居民遗传研究相关的伦理问题，并考虑了其中一些问题是如何在偏远土著社区目前正在进行的基因组研究项目中进行谈判的。我们考虑在澳大利亚运作的不同程度的土著研究治理如何影响该研究项目，并讨论是否有必要在土著和托雷斯海峡岛民社区进行基因研究的具体准则。