BACKGROUND & AIMS: BACKGROUND:Many apparently disparate risk factors have been implicated as causes of eating disorders. This study was designed to test the hypothesis that 2 broad classes of risk factors exist for bulimia nervosa: those that increase the risk for development of a psychiatric disorder in general and those that increase the risk of dieting. It was predicted that the latter are especially common among persons with bulimia nervosa.

METHODS:A case-control design was used involving 2 integrated comparisons. First, 102 subjects with bulimia nervosa were compared with 204 healthy control subjects without an eating disorder. Second, the same 102 subjects with bulimia nervosa were compared with 102 subjects with other psychiatric disorders. To reduce sampling bias, the subjects were recruited directly from the community. A broad range of putative risk factors was assessed.

RESULTS:The subjects with bulimia nervosa and the healthy control subjects differed in their rates of exposure to most of the putative risk factors. Far fewer differences were evident between the subjects with bulimia nervosa and the control subjects with other psychiatric disorders, although exposure to factors that were likely to increase the risk of dieting and to negative self-evaluation and certain parental problems (including alcohol use disorder) were substantially more common among those with bulimia nervosa.

CONCLUSIONS:The findings support the hypothesis that bulimia nervosa is the result of exposure to general risk factors for psychiatric disorder and risk factors for dieting. An unexpected finding was the particularly high rates of premorbid negative self-evaluation and certain parental problems among those with bulimia nervosa.

背景与目标： 背景 : 许多明显不同的危险因素被认为是饮食失调的原因。这项研究旨在检验以下假设: 神经性贪食症存在两大类危险因素: 通常增加精神疾病发展风险的因素和增加节食风险的因素。据预测，后者在神经性贪食症患者中尤其常见。
方法 : 使用了涉及2个综合比较的病例对照设计。首先，将102名患有神经性贪食症的受试者与204名没有进食障碍的健康对照受试者进行比较。其次，将患有暴食症的相同102受试者与患有其他精神疾病的102受试者进行比较。为了减少抽样偏差，直接从社区招募了受试者。评估了广泛的推定危险因素。
结果 : 患有神经性贪食症的受试者和健康对照受试者在暴露于大多数推定危险因素的比率上有所不同。神经性贪食症的受试者与其他精神疾病的对照受试者之间的差异要少得多，尽管暴露于可能增加节食风险的因素以及负面的自我评估和某些父母问题 (包括酒精使用障碍) 在神经性贪食症患者中更为普遍。
结论 : 研究结果支持以下假设: 神经性贪食症是暴露于精神疾病的一般危险因素和节食的危险因素的结果。一个意想不到的发现是，在神经性贪食症患者中，病前负面自我评估和某些父母问题的发生率特别高。

BACKGROUND & AIMS: :The prevalence of mRNAs coding for the sea urchin embryo regulatory factors P3A1 and P3A2 was measured by single-strand probe excess solution hybridization. P3A1 and P3A2 are not homologous proteins, though they both bind specifically to a particular cis-regulatory sequence. Interaction at this target site is known to be required for lineage-specific expression of an aboral ectoderm-specific gene and probably for several other genes as well. Genome blot hybridizations show that both factors are encoded by single-copy genes. Maternal mRNAs for both factors are present at less than 10(3) molecules per egg, which places them in the rare mRNA class. During development to the mesenchyme blastula stage, the amount of P3A1 mRNA (per embryo) increases severalfold while that of P3A2 remains approximately constant. Specification of the aboral ectoderm founder cells and of their initial patterns of gene expression must occur during early to mid-cleavage stage. Therefore, the regulatory proteins needed for this process must be produced by this stage. We show that the quantities of the P3A proteins that can be synthesized from the numbers of mRNA molecules present in the large blastomeres of the early embryo are sufficient to be functional, because these proteins will be accumulated in the nuclei. Thus maternal P3A1 or P3A2 proteins asre not required, nor were these detected in earlier studies. Furthermore, differential spatial (as well as temporal) distribution of both of these newly synthesized factor species could result from the unequal cleavage pattern utilized in the sea urchin egg.

背景与目标： : 通过单链探针过量溶液杂交测量编码海胆胚胎调节因子P3A1和P3A2的mrna的患病率。P3A1和P3A2不是同源蛋白，尽管它们都与特定的顺式调节序列特异性结合。已知该靶位点的相互作用对于外胚层特异性基因的谱系特异性表达以及其他几个基因也是必需的。基因组印迹杂交表明，这两个因子均由单拷贝基因编码。两种因子的母体mRNA在每个卵中存在的分子少于10(3) 个，这使它们处于稀有mRNA类别中。在发育到间充质囊胚阶段期间，P3A1 mRNA的量 (每个胚胎) 增加了几倍，而P3A2的量保持大致恒定。必须在早期至中期切割阶段对外胚层创始细胞及其基因表达的初始模式进行规范。因此，此过程所需的调节蛋白必须在此阶段产生。我们表明，可以从早期胚胎大卵裂球中存在的mRNA分子的数量合成的P3A蛋白的数量足以发挥功能，因为这些蛋白将积聚在细胞核中。因此，不需要母体P3A1或P3A2蛋白，在早期研究中也未检测到这些蛋白。此外，这两种新合成的因子物种的空间 (和时间) 分布差异可能是由于海胆卵中使用的不相等的卵裂模式造成的。

BACKGROUND & AIMS: STUDY OBJECTIVE:To examine the prevalence, symptomatology, risk factors, and other infections associated with urogenital chlamydial infection in pregnant teenagers. DESIGN:Retrospective case-control study by medical record review. SETTING:Prenatal care clinic for adolescents at University of Tennessee Medical Center, Knoxville, Tennessee. PARTICIPANTS:Pregnant adolescents younger than 19 years of age who were diagnosed with chlamydial infection on the first prenatal visit from 1988 to 1994 were studied. Pregnant adolescents of similar age and socioeconomic background who came in the same day for the first prenatal visit, but were not infected, made up the control group. INTERVENTION:Routine prenatal questionnaires regarding personal and medical histories, and routine prenatal screening, including pelvic examination with Papanicolaou (PAP) smear and laboratory investigations for common genital infections and sexual transmitted disease (STDs), were obtained. MAIN OUTCOME MEASURES:Analyzed the prevalence of chlamydial infection and compared the infected group to the control group with regard to race, behavioral factors, symptoms, prenatal screening results, other concurrent genital infections, and histories of STDs. RESULTS:Of a total population of 596 pregnant teenagers, 67 (11.24%) were infected with Chlamydia trachomatis. In multivariate analysis, black race (odds ratio [OR] = 4.01; 95% confidence interval [CI] = 1.74-9.23; p = 0.001) and greater gestational age at first prenatal visit (OR = 1.11; 95% CI = 1.04-1.18; p = 0.001) were independently associated with chlamydial infection. Age, marital status, number of pregnancies, smoking, alcohol abuse, drug abuse, age at first intercourse, and multiple sex partners were not associated with the infection. Likewise, the symptom of vaginal discharge (a complaint of > 70% in each group), other genital co-infections (found > 50% in each group, mainly candidiasis and bacterial vaginosis), abnormal PAP smears (found > 60% in each group) and histories of STDs or previous chlamydial infection were not significantly different between case and control groups. Human papillomavirus infection, trichomonal infection, and dysplasia or atypia were found more often in patients infected with chlamydia, but were not statistically significant. CONCLUSION:Pregnant adolescents in east Tennessee were at risk for chlamydial infection as well as for other genital infections and abnormal PAP smears. Routine prenatal chlamydial screening is warranted because of a lack of specific symptoms.

背景与目标：

BACKGROUND & AIMS: :Agricultural soils of two Italian maize farms were treated for five years with an industrially produced high-quality compost. Cattle manure and the usual mineral fertilizer were used for comparison purposes. The effects of the organic and mineral fertilizer treatments were studied by analyzing the compost and manure, cultured soils, and harvested material. The grain yield was also determined. Organic fertilization improved soil pH, CEC, content of organic matter and NPK. Soil respiration and N mineralization were found to be higher than in the purely mineral-treated soil. Plant K take-up was improved, whereas grain yield was not affected. It was confirmed that organic fertilization, particularly compost use, maintained and increased soil fertility. The study demonstrated the feasibility of using in loco analytical facilities to follow the entire recycling process-from waste to compost production-and the use of the final product in the field.

背景与目标： : 意大利两个玉米农场的农业土壤用工业生产的高质量堆肥处理了五年。牛粪和通常的矿物肥料用于比较目的。通过分析堆肥和肥料，培养的土壤和收获的材料，研究了有机和矿物肥料处理的效果。还确定了谷物产量。有机施肥改善了土壤pH，CEC，有机质和NPK的含量。发现土壤呼吸作用和氮矿化作用高于纯矿物处理的土壤。提高了植物的K用量，而不影响谷物产量。已经证实，有机施肥，特别是堆肥的使用，可以维持和提高土壤肥力。该研究证明了在loco分析设施中使用从废物到堆肥生产的整个回收过程以及在现场使用最终产品的可行性。

BACKGROUND & AIMS: UNLABELLED:The objective of the present study was to investigate whether the endogenous opioids are involved in the control of endothelin-1 release from the pituitary gland. To test this hypothesis we have measured the peripheral plasma concentration of ET-1 as well as the content of immunoreactive ET-1 (irET-1) in the pituitary in response to opioid receptors blockade in euhydrated and 24 h water-deprived Wistar-Kyoto rats. Placebo or naltrexone (50 micrograms/kg body wt.) were given i.v. in both groups. Trunk blood was collected to determine hematocrit, plasma sodium and ET-1 levels (RIA). Immunostaining of ET-1 in the whole pituitary glands was performed by colloidal gold labeling. The quantitative analysis of irET-1 was carried out under a light microscope using a computerized image analyzer (MultiScan). RESULTS:(1) Twenty-four-hour dehydration resulted in marked increase of peripheral concentration of ET-1. Naltrexone injection induced a significant elevation of ET-1 plasma concentration in both, dehydrated and control animals. (2) The content of irET-1 in anterior and intermediate lobes of the pituitary in dehydrated rats was markedly higher than in control group. (3) Naltrexone injection caused a rapid and significant reduction irET-1 within the anterior, intermediate and posterior lobes in dehydrated and control animals. CONCLUSIONS:(1) An elevation of irET-1 in the pituitary gland and peripheral circulation in dehydrated animals may play a role in maintaining of water-electrolyte balance. (2) The mu-opioid system appears to control the ET-1 release from the pituitary in normal and dehydrated animals.

背景与目标：

BACKGROUND & AIMS: :Recent findings suggest a pivotal role for mitochondria-associated hexokinase in the regulation of apoptosis in animal cells. In this study, virus-induced gene silencing (VIGS) of a hexokinase-encoding Hxk1 caused necrotic lesions on leaves, abnormal leaf morphology, and retarded plant growth in Nicotiana benthamiana. Hxk1 was associated with the mitochondria, and this association required the N-terminal membrane anchor. VIGS of Hxk1 reduced the cellular glucose-phosphorylating activity to approximately 31% of control levels without changing the fructose-phosphorylating activity and did not alter hexose phosphate content severely. The affected cells showed programmed cell death (PCD) morphological markers, including nuclear condensation and DNA fragmentation. Similar to animal cell apoptosis, cytochrome c was released into the cytosol and caspase-9- and caspase-3-like proteolytic activities were strongly induced. Furthermore, based on flow cytometry, Arabidopsis thaliana plants overexpressing Arabidopsis HXK1 and HXK2, both of which are predominantly associated with mitochondria, exhibited enhanced resistance to H(2)O(2)- and alpha-picolinic acid-induced PCD. Finally, the addition of recombinant Hxk1 to mitochondria-enriched fractions prevented H(2)O(2)/clotrimazole-induced cytochrome c release and loss of mitochondrial membrane potential. Together, these results show that hexokinase critically regulates the execution of PCD in plant cells, suggesting a link between glucose metabolism and apoptosis.

背景与目标： : 最近的发现表明线粒体相关的己糖激酶在调节动物细胞凋亡中起着关键作用。在这项研究中，编码己糖激酶的Hxk1的病毒诱导的基因沉默 (VIGS) 导致烟草叶片坏死病变，叶片形态异常和植物生长受阻。Hxk1与线粒体相关，这种关联需要N端膜锚定。Hxk1的VIGS将细胞葡萄糖磷酸化活性降低至对照水平的约31%，而不改变果糖磷酸化活性，并且不会严重改变己糖磷酸含量。受影响的细胞显示出程序性细胞死亡 (PCD) 形态标记，包括核浓缩和DNA片段化。与动物细胞凋亡相似，细胞色素c被释放到细胞质中，并强烈诱导了caspase-9和caspase-3-like的蛋白水解活性。此外，基于流式细胞仪，过度表达拟南芥HXK1和HXK2的拟南芥植物均主要与线粒体相关，对H(2)O(2)-和 α-吡啶甲酸诱导的PCD表现出增强的抗性。最后，将重组Hxk1添加到富含线粒体的级分中，可防止H(2)O(2)/克霉唑诱导的细胞色素c释放和线粒体膜电位丧失。总之，这些结果表明，己糖激酶在植物细胞中严格调节PCD的执行，表明葡萄糖代谢与细胞凋亡之间存在联系。

BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

背景与目标：

BACKGROUND & AIMS: :The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.

背景与目标： : 卵巢类固醇激素雌激素 (E2) 在体内引起多种全身和子宫性反应。例如，向卵巢切除 (Ovx) 和性不成熟的啮齿动物施用E2会导致子宫特异性炎症浸润。在这项研究中，我们定量了从成年Ovx对照和E2-treated C57BL/6J，C3H/HeJ和 (C57BL/6J x C3H/HeJ) (B6C3) F1杂交小鼠获得的子宫中嗜酸性粒细胞和BM8，Ia和CD4细胞的数量。E2处理后，所有这三种菌株的子宫嗜酸性粒细胞和BM8巨噬细胞数量均显着增加。然而，与C3H/HeJ相比，C57BL/6J和B6C3 F1杂交小鼠的浸润嗜酸性粒细胞和巨噬细胞数量更多。对Ia和CD4细胞的类似分析表明，E2处理下调或不影响所有三种菌株中此类细胞的数量。使用 (C57BL/6J x C3H/HeJ) x C3H/HeJ回交群体的基因组排斥图谱将Est1定位为4号染色体，Est1是控制E2治疗后子宫浸润的嗜酸性粒细胞数量的主要基因座。此外，还检测到与10号和16号染色体上的标记基因座的暗示连锁，并提供了基因座相互作用的证据。我们的结果最终证明了E2-regulated/依赖性反应可以在遗传上控制，这表明在E2的正常和病理作用中观察到的表型变异可能部分归因于遗传成分。

BACKGROUND & AIMS: :A transcript (RNA I) from ColE1 inhibits initiation of replication of the plasmid DNA by binding to the precursor of the primer RNA (RNA II). The ability of RNA I to inhibit replication is altered by the presence of a plasmid-specified small protein, Rom. In vitro, RNA I binds to RNA II to form a very unstable complex, C*. Binding of a single molecule of Rom converts C* to a more stable complex, Cm*. Each of these complexes, C* or Cm*, transforms to a more stable complex, C** or Cm**, respectively. While formation of complex C* or Cm* is inferred from the inhibition of binding caused by a second RNA I species, that of complex C** or Cm** is detected by alteration of RNase sensitivity. Complex C* converts to complex Cm* very rapidly upon addition of Rom to the medium and complex Cm* converts to complex C* very rapidly by removal of Rom from the medium. On the other hand, complexes C** and Cm** do not rapidly interconvert, but can eventually transform to the same stable final product. Thus, Rom affects binding of RNA I to RNA II through conversion of a very unstable early intermediate to a more stable complex, creating a second pathway for their stable binding.

背景与目标： : 来自ColE1的转录本 (RNA I) 通过与引物RNA (RNA II) 的前体结合来抑制质粒DNA的复制启动。RNA I抑制复制的能力因质粒指定的小蛋白Rom的存在而改变。在体外，RNA I与RNA II结合形成非常不稳定的复合物C *。单个Rom分子的结合将C * 转化为更稳定的复合物Cm *。这些配合物C * 或Cm * 中的每一个分别转换为更稳定的配合物C ** 或Cm **。虽然从第二种RNA I物种引起的结合抑制推断出复合物C * 或Cm * 的形成，但通过RNase敏感性的改变来检测复合物C ** 或Cm ** 的形成。将Rom添加到介质中时，复杂C * 非常迅速地转换为复杂Cm *，而通过从介质中删除Rom，复杂Cm * 非常迅速地转换为复杂C *。另一方面，络合物C ** 和Cm ** 不会快速互转，但最终可以转化为相同的稳定最终产物。因此，Rom通过将非常不稳定的早期中间体转化为更稳定的复合物来影响RNA I与RNA II的结合，从而为它们的稳定结合创造了第二条途径。

BACKGROUND & AIMS: Environmental pollution has become a major concern for the future of life on our planet; medical care, especially in hospitals, contributes significantly to this pollution. The increasing usage of highly-developed medical devices, drugs and disposable products are a drain on natural resources as well as financial ones. In this situation, it is a major task for hospital epidemiologists to maintain high standards of hygiene while reducing environmental pollution, reducing consumption of limited natural resources, and minimizing costs. The reduction of hospital waste, the control of polluting and toxic emissions, the avoidance of unnecessary disinfection procedures and disposables, the implementation of energy and water saving technologies are practicable measures in hospital ecology. To realize a sustainable development within hospitals, it is necessary that the need to maintain a balance between effective infection control and a good ecological environment is recognized and supported by health-care workers and the hospital management.

背景与目标： 环境污染已成为地球生命未来的主要问题; 医疗保健，尤其是医院的医疗保健，对这种污染有很大影响。高度发达的医疗设备，药品和一次性产品的使用日益增加，既消耗了自然资源，也消耗了金融资源。在这种情况下，医院流行病学家的主要任务是在减少环境污染的同时保持高标准的卫生，减少对有限自然资源的消耗并最大程度地降低成本。减少医院废物，控制污染和有毒排放物，避免不必要的消毒程序和一次性用品，实施节能节水技术是医院生态中的可行措施。为了实现医院内部的可持续发展，有必要在有效的感染控制和良好的生态环境之间保持平衡的需要得到医护人员和医院管理层的认可和支持。

BACKGROUND & AIMS: :The skin as a barrier and immune organ is exposed to omnipresent environmental challenges such as irradiation or chemical and biologic hazards. Neuropeptides released from cutaneous nerves or skin and immune cells in response to noxious stimuli are mandatory for a fine-tuned regulation of cutaneous immune responses and tissue maintenance and repair. They initialize host immune responses, but are equally important for counter regulation of proinflammatory events. Interaction of the nervous and immune systems occurs both locally - at the level of neurogenic inflammation and immunocyte activation - and centrally - by controlling inflammatory pathways such as mononuclear activation or lymphocyte cytokine secretion. Consequently, a deregulated neurogenic immune control results in disease manifestation and frequently accompanies chronic development of cutaneous disorders. The current understanding, therapeutic options, and open questions of the role that neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide, neuropeptide Y, or others play in these events are discussed. Progress in this field will likely result in novel therapies for the management of diseases characterized by deregulated inflammation, tissue remodeling, angiogenesis, and neoplasm.

背景与目标： : 皮肤作为屏障和免疫器官暴露于无所不在的环境挑战，如辐射或化学和生物危害。响应有害刺激从皮肤神经或皮肤和免疫细胞释放的神经肽对于微调皮肤免疫反应以及组织维护和修复是必不可少的。它们初始化宿主免疫反应，但对于反调节促炎事件同样重要。神经和免疫系统的相互作用通过控制炎症途径 (例如单核激活或淋巴细胞细胞因子分泌) 在局部发生-在神经源性炎症和免疫细胞激活水平上-在中枢发生。因此，放松的神经源性免疫控制会导致疾病表现，并经常伴随皮肤疾病的慢性发展。讨论了神经肽 (例如p物质，降钙素基因相关肽，血管活性肠肽/垂体腺苷酸环化酶激活多肽，神经肽Y或其他) 在这些事件中的作用的当前理解，治疗选择和开放性问题。该领域的进展可能会导致新的疗法来管理以炎症，组织重塑，血管生成和肿瘤为特征的疾病。

BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

背景与目标： 最近的基因组搜索表明，许多基因座与I型糖尿病易感性之间存在推定的联系。据报道，染色体2q31-35区域与I型糖尿病的易感性有关，并被认为包含多个糖尿病易感性位点。这些候选基因包括HOXD基因簇，BETA2，CTLA4，CD28，IGFBP2和igfbp5。需要在人群和家庭中进行关联研究，以确认和/或确定实际的易感性位点。我们在此报告了HOXD8，BETA2和IGFBP5的几个先前未知的DNA多态性，我们将其与先前已知的HOXD8和CTLA4的多态性一起使用，以测试这些候选基因座是否是染色体2q31-35上的易感基因。使用病例对照设计和随后的家庭关联方法来确认关联，我们没有发现证据表明这些候选基因与I型糖尿病的易感性有关。

BACKGROUND & AIMS: :In some randomized (drug versus placebo) clinical trials, the estimand of interest is the between-treatment difference in population means of a clinical endpoint that is free from the confounding effects of "rescue" medication (e.g., HbA1c change from baseline at 24 weeks that would be observed without rescue medication regardless of whether or when the assigned treatment was discontinued). In such settings, a missing data problem arises if some patients prematurely discontinue from the trial or initiate rescue medication while in the trial, the latter necessitating the discarding of post-rescue data. We caution that the commonly used mixed-effects model repeated measures analysis with the embedded missing at random assumption can deliver an exaggerated estimate of the aforementioned estimand of interest. This happens, in part, due to implicit imputation of an overly optimistic mean for "dropouts" (i.e., patients with missing endpoint data of interest) in the drug arm. We propose an alternative approach in which the missing mean for the drug arm dropouts is explicitly replaced with either the estimated mean of the entire endpoint distribution under placebo (primary analysis) or a sequence of increasingly more conservative means within a tipping point framework (sensitivity analysis); patient-level imputation is not required. A supplemental "dropout = failure" analysis is considered in which a common poor outcome is imputed for all dropouts followed by a between-treatment comparison using quantile regression. All analyses address the same estimand and can adjust for baseline covariates. Three examples and simulation results are used to support our recommendations.

背景与目标： : 在一些随机 (药物与安慰剂) 临床试验中，感兴趣的估计是临床终点的人群治疗间差异，该临床终点不受 “抢救” 药物的混杂作用 (例如，hbA1c在24周时与基线相比的变化，无论是否或何时终止分配的治疗，在没有抢救药物的情况下都会观察到).在这种情况下，如果某些患者在试验中过早退出试验或开始使用抢救药物，则会出现数据丢失的问题，后者需要丢弃抢救后的数据。我们警告说，常用的混合效应模型重复测量分析与随机假设的嵌入缺失可以提供对上述感兴趣估计的夸大估计。发生这种情况的部分原因是对药物组中 “辍学” (即缺少感兴趣的终点数据的患者) 过于乐观的均值进行了隐含的估算。我们提出了一种替代方法，其中将药物组辍学的缺失平均值明确替换为安慰剂下的整个终点分布的估计平均值 (主要分析) 或在临界点框架内的一系列越来越保守的平均值 (敏感性分析); 不需要患者水平的估算。考虑了补充的 “辍学 = 失败” 分析，其中对所有辍学进行了共同的不良结果估算，然后使用分位数回归进行治疗之间的比较。所有分析都针对相同的估计，并且可以针对基线协变量进行调整。使用了三个示例和仿真结果来支持我们的建议。

BACKGROUND & AIMS: :The purpose of this study was to compare preferred facial profiles rated by different age groups. An average profile of each gender was constructed from subjects with normal occlusions. Each average profile was located in the centre, and then the lips were protruded or retruded in six 1mm increments in each direction. 70 lay people were divided into 3 groups: young adult (20-39 years); middle-aged (40-54 years); and senior (55-70 years). They were asked to rank their 3 most preferred profiles for each gender. The distribution of the most pleasing profile was compared according to age groups by the Kruskal-Wallis test and according to the rater's gender by the Mann-Whitney U-test. There was a significant difference between the three age groups regarding the preferred male and female profiles (P<0.001). Both the middle-aged and the senior groups tended to select a slightly more retruded lip/flat profile than the young adult group. There was no gender dimorphism in the selection of the preferred profile. The young adult group preferred the straight profile while the middle-aged and senior groups favoured the slightly retruded profile. This may provide useful information for treatment planning in orthodontics and orthognathic surgery.

背景与目标： : 这项研究的目的是比较不同年龄段的首选面部特征。从正常闭塞的受试者中构建每个性别的平均特征。每个平均轮廓位于中心，然后在每个方向上以六个1毫米的增量突出或重放嘴唇。70名外行人分为3组: 年轻人 (20-39岁); 中年 (40-54岁); 和老年人 (55-70岁)。他们被要求对每个性别的3个最喜欢的个人资料进行排名。通过Kruskal-Wallis测试根据年龄组比较了最令人愉悦的个人资料的分布，并通过Mann-Whitney u- test根据评估者的性别进行了比较。三个年龄组在首选男性和女性特征方面存在显着差异 (P<0.001)。与年轻的成年组相比，中老年组和老年组都倾向于选择略胜一筹的嘴唇/扁平轮廓。在选择首选特征时没有性别二态性。年轻的成年组更喜欢直率的轮廓，而中老年组则更喜欢略微被重述的轮廓。这可能为正畸和正颌手术的治疗计划提供有用的信息。

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放血的人，因此应进行更严格的研究。