BACKGROUND & AIMS: BACKGROUND:The purpose of this study was to explore the association of five factors personality traits, as predictor variables, with the anxiety and depression as joint dependent variables in an Iranian adult population. SUBJECTS AND METHODS:A total of 3175 subjects living in Isfahan participated in this cross-sectional population-based study (SEPAHAN) and completed self-administered questionnaires about demographic, life style, gastrointestinal disorders, personality traits, social support, and psychological problems. Data was analyzed using bivariate multiple binary logistic regression in R Free statistical software. RESULTS:The results indicated high scores of neuroticisms increase the risk of anxiety and depression after adjustment for the potential confounders in total sample (OR (95% CI): 1.22 (1.19-1.24) and 1.19 (1.17-1.21), respectively) as well as in both male and female. In contrast, joint inverse associations were found between anxiety and depression with high extraversion (OR (95% CI): 0.90 (0.88-0.92) and 0.91 (0.89-0.92), respectively), agreeableness (0.93 (0.91-0.96) and 0.94 (0.92-0.96) respectively) and conscientiousness scores (0.95 (0.93-0.97) and 0.95 (0.94-0.97) respectively) as well as in both male and female. Furthermore, higher scores of openness had significant inverse association with depression in male. CONCLUSION:The present study indicated that higher scores of neuroticism, however lower extraversion, conscientiousness and agreeableness scores are risk factors for both anxiety and depression in Iranian adult population. It is suggested to perform family studies or twin and genetic association studies with considering combinations of personality traits (personality styles), and also measuring personality traits at the facet level.

背景与目标： 背景：本研究的目的是探讨伊朗成年人口中五项因素的人格特质（作为预测变量）与焦虑和抑郁作为联合因变量之间的关系。
受试者与方法：总共3175名居住在伊斯法罕的受试者参加了这项基于人群的横断面研究（SEPAHAN），并完成了有关人口统计学，生活方式，胃肠道疾病，人格特质，社会支持和心理问题的自我管理问卷。在R Free统计软件中使用双变量多元二元logistic回归分析数据。
结果：结果表明，对总样本中潜在的混杂因素进行调整后，高分的神经质增加了焦虑和抑郁的风险（OR（95％CI）：1.22（1.19-1.24）和1.19（1.17-1.21））以及男性和女性。相比之下，焦虑和抑郁之间的关节逆向关联具有高外向性（OR（95％CI）：0.90（0.88-0.92）和0.91（0.89-0.92）），顺应性（0.93（0.91-0.96）和0.94） （分别为0.92-0.96）和尽责分数（分别为0.95（0.93-0.97）和0.95（0.94-0.97））以及男性和女性。此外，较高的开放度得分与男性抑郁症呈显着的负相关。
结论：本研究表明，神经质评分较高，但外向性，尽责性和愉悦性评分较低是伊朗成年人口焦虑和抑郁的危险因素。建议进行家庭研究或双胞胎和遗传关联研究，同时考虑人格特质（人格风格）的组合，并在层面上测量人格特质。

BACKGROUND & AIMS: BACKGROUND:When there are structural relationships between outcomes reported in different trials, separate analyses of each outcome do not provide a single coherent analysis, which is required for decision-making. For example, trials of intrapartum anti-bacterial prophylaxis (IAP) to prevent early onset group B streptococcal (EOGBS) disease can report three treatment effects: the effect on bacterial colonisation of the newborn, the effect on EOGBS, and the effect on EOGBS conditional on newborn colonisation. These outcomes are conditionally related, or nested, in a multi-state model. This paper shows how to exploit these structural relationships, providing a single coherent synthesis of all the available data, while checking to ensure that different sources of evidence are consistent. RESULTS:Overall, the use of IAP reduces the risk of EOGBS (RR: 0.03; 95% Credible Interval (CrI): 0.002-0.13). Most of the treatment effect is due to the prevention of colonisation in newborns of colonised mothers (RR: 0.08, 95% CrI: 0.04-0.14). Node-splitting demonstrated that the treatment effect calculated using only direct evidence was consistent with that predicted from the remaining evidence (p = 0.15). The findings accorded with previously published separate meta-analyses of the different outcomes, once these are re-analysed correctly accounting for zero cells. CONCLUSION:Multiple outcomes should be synthesised together where possible, taking account of their structural relationships. This generates an internally coherent analysis, suitable for decision making, in which estimates of each of the treatment effects are based on all available evidence (direct and indirect). Separate meta-analyses of each outcome have none of these properties.

背景与目标： 背景：当在不同试验中报告的结果之间存在结构关系时，对每个结果的单独分析不会提供决策所需的单个连贯分析。例如，为防止早发性B组链球菌（EOGBS）疾病而进行的产前抗菌预防（IAP）试验可以报告三种治疗效果：对新生儿细菌定植的影响，对EOGBS的影响以及对有条件的EOGBS的影响在新生儿殖民地。这些结果在多状态模型中有条件地关联或嵌套。本文展示了如何利用这些结构关系，对所有可用数据进行单一连贯的综合，同时检查以确保不同证据来源是一致的。
结果：总体而言，IAP的使用降低了EOGBS的风险（RR：0.03； 95％可信区间（CrI）：0.002-0.13）。大多数治疗效果归因于对定植母亲的新生儿定植的预防（RR：0.08，95％CrI：0.04-0.14）。淋巴结清扫显示仅使用直接证据计算的治疗效果与根据其余证据预测的效果一致（p = 0.15）。一旦正确地重新分析了零细胞，这些结果就与先前发表的不同结果的单独荟萃分析相符。
结论：在可能的情况下，应综合多种结果，并考虑其结构关系。这会产生适合决策的内部连贯分析，其中对每种治疗效果的估计均基于所有可用证据（直接和间接）。每个结果的单独荟萃分析均不具备这些属性。

BACKGROUND & AIMS: BACKGROUND:It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations. AIMS:To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence. METHOD:Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study). RESULTS:Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA. CONCLUSIONS:A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.

背景与目标： 背景：目前尚不确定精神分裂症中使用抗精神病药长效注射（LAI）是否比口服制剂具有更好的临床效果。
目的：检查先前的治疗提供途径对治疗结果的影响，以及是否依从性可以缓解任何差异。
方法：分析两项实用的一年期临床试验的数据，其中将精神分裂症患者随机分为口服第一代抗精神病药（FGA）或非氯氮平第二代抗精神病药（SGA，CUtLASS 1研究），或非氯氮平SGA或氯氮平（CUtLASS 2研究）。
结果：在两项试验中，随机分组前，有43％（n = 155）的受试者被处方FGA-LAI。在1年的随访中，与口服药物相比，他们的生活质量，症状和整体功能改善不明显。这种差异仅限于被评定为低于持续坚持的随机分配的患者。如果将患者随机分配给氯氮平而不是另一种SGA，则可以改善LAI预随机化患者的相对较差的改善。从基线时的LAI随机分配到非氯氮平口服SGA而不是口服FGA没有优势。
结论：与从一种口服抗精神病药转换为另一种口服抗精神病药相比，从LAI随机转为口服抗精神病药与1年随访期的临床和功能结局较差有关。这种作用似乎通过坚持而得到缓解，并且可能不会扩展到使用氯氮平。这对临床试验设计具有影响：与参与者随机分配的药物相比，从参与者中随机分配的药物可能会产生更大的影响。

BACKGROUND & AIMS: BACKGROUND:In the United States, chronic obstructive pulmonary disease (COPD) diagnosis is often a lengthy process, and consequently results in delays in treatment in early stages. Disease progression and complication may result in increased levels of healthcare service use. To understand the economic burden of COPD prior to diagnosis in the U.S., trends in utilization and costs during the period before initial COPD diagnosis were compared with matched controls. METHODS:A retrospective case-control study was conducted using medical and pharmacy claims data from a large managed care health plan representing a base population of over 30 million covered lives in the U.S. COPD patients with at least 12 months of continuous enrollment and aged 40 years or older were identified (n=28,968) and matched to up to three random controls (n=81,322) by age, gender, region of plans and index date. Multivariate regression models were used to estimate average incremental service use and cost between COPD patients and controls. Moreover, trends in utilization and costs for the COPD patients were examined over 36 months before diagnosis. RESULTS:COPD patients used 1.5-1.6 times more inpatient/emergency department (IP/ED) services and office visits compared to control patients. The average incremental annual costs for IP/ED services, office visits, and medical and pharmacy services were estimated at $550, $238, $1438 and $401, respectively, after adjusting for age, gender, region and comorbid conditions. The 36-month trend analysis showed that COPD patients' healthcare utilization and costs increased gradually over time, often with a marked increase in the month before COPD diagnosis. CONCLUSIONS:COPD patients in the U.S. consumed substantial healthcare services and costs prior to diagnosis. More timely diagnosis and subsequent treatment may avoid costly healthcare utilization and unnecessary mortality and morbidity post-diagnosis.

背景与目标： 背景：在美国，慢性阻塞性肺疾病（COPD）的诊断通常是一个漫长的过程，因此会导致早期治疗的延迟。疾病进展和并发症可能导致医疗服务使用水平提高。为了了解在美国进行诊断之前COPD的经济负担，我们将COPD初次诊断之前的使用率和成本趋势与匹配的对照进行了比较。
方法：一项回顾性病例对照研究是使用来自大型管理式医疗保健计划的医疗和药房索赔数据进行的，该数据代表了美国COPD患者中至少有3,000万人的基本生命，他们连续入组至少12个月，年龄40岁。年龄，性别，计划区域和索引日期被确定为≥（28,968）岁或更大（n = 81,322），并与多达三个随机对照匹配（n = 81,322）。多变量回归模型用于估计COPD患者和对照组之间的平均增量服务使用和费用。此外，在诊断前36个月内检查了COPD患者的使用率和费用趋势。
结果：与对照患者相比，COPD患者使用住院/急诊科（IP / ED）服务和办公室就诊的次数多1.5-1.6倍。在根据年龄，性别，地区和共病条件进行调整后，IP / ED服务，办公室就诊以及医疗和药学服务的平均年度增量成本分别为550美元，238美元，1438美元和401美元。为期36个月的趋势分析显示，COPD患者的医疗保健利用率和费用随着时间的推移逐渐增加，通常在COPD诊断前一个月就显着增加。
结论：在美国，COPD患者在诊断之前已消耗了大量的医疗保健服务和费用。更及时的诊断和后续治疗可以避免昂贵的医疗保健费用以及诊断后不必要的死亡率和发病率。

BACKGROUND & AIMS: :The care and management of hospitalized insanity acquittees can be quite challenging. As patients progress in treatment, clinicians must invariably address whether the patient is ready to be returned to the community, balancing the liberty interests of the acquittee with the protection of society. The process by which this determination is made is far from simple and involves review of clinical interview and collateral information, identification of indicators of outcome post-discharge, and the use of structured risk assessment instruments. The decision to release an acquittee conditionally is also influenced by an array of factors that emanate from within the clinician, within the institution, the mental health system, the courts, and the broader society. While such biases affect a clinician's objectivity, they are also a natural part of the evaluation process. Their identification is essential so that the degree to which such biases influence the conditional release decision can be more fully understood and addressed.

背景与目标： ：住院的精神错乱患者的护理和管理可能非常具有挑战性。随着患者治疗的进展，临床医生必须始终解决患者是否准备好返回社区，从而在大法官的自由利益与社会保护之间取得平衡。进行此确定的过程远非简单，需要审查临床访谈和附带信息，确定出院后结果指标以及使用结构化风险评估工具。从临床医生内部，机构内部，精神卫生系统，法院和更广泛的社会中产生的一系列因素也影响有条件释放无罪释放者的决定。尽管这种偏见影响了临床医生的客观性，但它们也是评估过程的自然组成部分。它们的识别是必不可少的，以便可以更充分地理解和解决这种偏见影响条件释放决策的程度。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Using an instrument to measure physical functioning that was normed to the U.S. population, data were obtained from patients with a new diagnosis of breast, colon, lung, and prostate cancer. Two questions were addressed: (a) after controlling for age, and number of comorbid conditions, do site and stage of cancer predict functional limitations prior to diagnosis; (b) using age adjusted national norms on physical functioning, how well do age, number of comorbid conditions, stage, treatment and cluster of symptoms (pain, fatigue, and insomnia) explain changes in physical function between 3 months prior to and 8 weeks following diagnosis? METHODS:Patients 65 years of age and older were accrued from 24 community oncology settings. Consenting patients were interviewed within 8 weeks of initial treatment. The SF-36 was used to measure physical functioning. Comorbidity and symptom experience were assessed through patient report and site and stage of cancer from record audits. RESULTS:Prior to diagnosis of cancer, patients were comparable in physical functioning to the U.S. population aged 55-64, a full decade younger than the sample of cancer patients. Site and stage of disease did not account for variations in physical functioning prior to diagnosis. Compared against national norms, patients with more extensive treatments (surgery plus adjuvant therapy) reported greater loss in functioning. Pain, fatigue, and insomnia had a consistent and significant effect on losses in functioning unrelated to patients' treatments or their comorbid conditions. CONCLUSIONS:Site and stage of cancer prior to diagnosis do not affect functioning. Older cancer patients report higher functioning than their counterparts in the U.S. population. Changes in functioning following diagnosis varied by cancer site. Treatments were related to loss in functioning, but comorbidity was not. Pain, fatigue, and insomnia were significant and independent predictors of change in patient functioning. This underscores the importance of interventions to manage symptoms early in the course of treatment for individuals.

背景与目标： 背景与目的：使用一种针对美国人群的生理功能测量仪器，从乳腺癌，结肠癌，肺癌和前列腺癌的新诊断患者中获取数据。解决了两个问题：（a）在控制了年龄和合并症的数量之后，癌症的部位和阶段是否可以在诊断之前预测功能限制？ （b）使用经过年龄调整的身体机能国家规范，年龄，合并症数，阶段，治疗和症状（疼痛，疲劳和失眠）的状况如何，可以解释在3个月前和8周之间身体机能的变化以下诊断？
方法：来自24个社区肿瘤科的患者年龄在65岁及以上。同意患者在初次治疗后8周内接受采访。 SF-36用于测量身体机能。通过患者报告以及记录审核的癌症部位和阶段来评估合并症和症状经验。
结果：在诊断出癌症之前，患者的身体功能与美国55-64岁的人群相当，比癌症患者的年龄年轻了整整十年。疾病的部位和阶段并未解释诊断前身体机能的变化。与国家标准相比，接受更广泛治疗（手术加辅助治疗）的患者报告功能丧失更大。疼痛，疲劳和失眠对与患者的治疗或合并症无关的功能丧失具有持续而显着的影响。
结论：诊断前的部位和癌症分期不影响功能。较年长的癌症患者报告说其功能比美国人群中的同行患者更高。诊断后功能的变化因癌症部位而异。治疗与功能丧失有关，但合并症无关。疼痛，疲劳和失眠是患者功能变化的重要且独立的预测因子。这强调了在个体治疗过程中早期管理症状的干预措施的重要性。

BACKGROUND & AIMS: BACKGROUND:Oestrogens usually stimulate the progression of oestrogen receptor (ER)-positive breast cancer. Paradoxically, high-dose oestrogens suppress the growth of these tumours in certain circumstances. METHODS:We prospectively examined the efficacy and safety of ethinylestradiol treatment (3 mg per day oral) in postmenopausal patients with advanced or recurrent ER-positive breast cancer who had previously received endocrine therapies, especially those with resistance to aromatase inhibitors. RESULTS:Eighteen patients were enrolled with the median age of 63 years and the mean observation time of 9.2 months. Three cases withdrew within 1 week due to oestrogen flare reactions with nausea, fatigue and muscle-skeletal pain. The response rate was 50% (9 out of 18), and the clinical benefit rate was 56% (10 out of 18). The stable disease (<6 months) was 17% (3 out of 18) and another 2 cases were judged as progressive disease. Time-to-treatment failure including 2 on treatment was a median of 5.6 months (range 0.1 to 14.5(+)). Although vaginal bleeding or endometrial thickening was observed in patients receiving long-term treatment, there were no severe adverse events, such as deep venous thrombosis or other malignancies. CONCLUSION:Although the mechanism of this treatment has not been fully understood, our data may contribute to change the common view of late-stage endocrine therapy.

背景与目标： 背景：雌激素通常刺激雌激素受体（ER）阳性乳腺癌的进展。矛盾的是，大剂量雌激素在某些情况下会抑制这些肿瘤的生长。
方法：我们前瞻性地研究了乙炔雌二醇治疗（每天口服3 mg）在绝经后患有晚期或复发性ER阳性乳腺癌的绝经后患者中的有效性和安全性，这些患者先前曾接受过内分泌治疗，尤其是那些对芳香酶抑制剂具有抗药性的患者。
结果：18例患者的中位年龄为63岁，平均观察时间为9.2个月。 1星期内有3例患者因雌激素反响，恶心，疲劳和肌肉骨骼疼痛而退出治疗。缓解率为50％（18个中的9个），临床受益率为56％（18个中的10个）。稳定的疾病（<6个月）为17％（18个中的3个），另外2例被判断为进行性疾病。包括2个治疗在内的治疗失败时间中位数为5.6个月（范围为0.1到14.5（））。尽管在接受长期治疗的患者中观察到阴道出血或子宫内膜增厚，但没有发生严重的不良事件，如深静脉血栓形成或其他恶性肿瘤。
结论：尽管尚未完全了解这种治疗的机制，但我们的数据可能有助于改变晚期内分泌治疗的普遍看法。

BACKGROUND & AIMS: :The breakdown of food in the mouth during mastication can be described in terms of two parameters: a breakage function, which describes the fragmentation of food after a bite, and a selection function which defines the probability of particle fracture. The non-zero value of the selection function depends on the manipulation of food particles by the tongue. Little, however, is known about this. As a first step, this study investigated the manipulation of wax sheets of differing sizes and shapes by the tongue after ingestion. It was found that subjects tended to orientate rectangular and square wax wafers so that the long axis of the particle was parallel to the tooth row, independent of the initial orientation given when they were introduced into the mouth. Circular wafers were randomly oriented relative to initial orientation. If this could be extrapolated to the start of mastication, then it suggests that the tongue tends to align food particles so that the post-canines produce close to the greatest surface area possible by fragmenting them along their longest axis.

背景与目标： ：咀嚼过程中食物在口腔中的分解可以用两个参数来描述：破损函数（描述叮咬后食物的碎裂）和选择函数（定义颗粒破碎的可能性）。选择函数的非零值取决于舌头对食物颗粒的操纵。然而，对此知之甚少。第一步，这项研究调查了摄入后舌头对不同大小和形状的蜡纸的处理方法。结果发现，受试者倾向于对矩形和方形蜡片进行取向，以使颗粒的长轴与牙齿排平行，而与将其引入口腔时的初始取向无关。圆形晶圆相对于初始取向随机取向。如果可以将其推断为咀嚼开始，则表明舌头倾向于对齐食物颗粒，从而使犬后沿其最长轴破碎，从而产生接近最大表面积的犬齿。

BACKGROUND & AIMS: :Extracorporeal Photochemotherapy (ECP) is a widely applied anti-cancer immunotherapy for patients with cutaneous T cell lymphoma (CTCL). By using apoptotic malignant cells as a source of patient-specific tumor antigen, it enables clinically relevant and curative anti-CTCL immunity, with potential efficacy in other tumors. Currentmethods to track patient-specific responses are tedious, and new methods are needed to assess putative global immunity. We developed a clinically practical method to assess antigen-specific T cell activation that does not rely on knowledge of the particular antigen, thereby eliminating the requirement for patient-specific reagents. In the OT-I transgenic murine system, we quantified calcium flux to reveal early T cell engagement by antigen presenting cells constitutively displaying a model antigenic peptide, ovalbumin (OVA)-derived SIINFEKL. We detected calcium flux in OVA-specific T cells, triggered by specific T cell receptor engagement by SIINFEKL peptide-loaded DC. This approach led to sensitive detection of antigen-specific calcium flux (ACF) down to a peptide-loading concentration of ∼10-3uM and at a frequency of ∼0.1% OT-I cells among wild-type (WT), non-responding cells. Antigen-specific T cells were detected in spleen, lymph nodes, and peripheral blood after adoptive transfer into control recipient mice. Methods like this for assessing therapeutic response are lacking in patients currently on immune-based therapies, such as ECP, where assessment of clinical response is made by delayed measurement of the size of the malignant clone. These findings suggest an early, practical way to measure therapeutically-induced anti-tumor responses in ECP-treated patients that have been immunized against their malignant cells.

背景与目标： ：体外光化学疗法（ECP）是针对皮肤T细胞淋巴瘤（CTCL）患者的广泛应用的抗癌免疫疗法。通过使用凋亡性恶性细胞作为患者特异性肿瘤抗原的来源，它可以实现临床相关且可治愈的抗CTCL免疫力，并在其他肿瘤中具有潜在的疗效。追踪患者特定反应的当前方法是乏味的，并且需要新的方法来评估推定的总体免疫力。我们开发了一种临床实用的方法来评估抗原特异性T细胞活化，该方法不依赖于特定抗原的知识，从而消除了对患者特异性试剂的需求。在OT-I转基因鼠类系统中，我们量化钙通量以揭示抗原呈递细胞的早期T细胞参与，该抗原呈递细胞组成性地显示模型性抗原肽，卵清蛋白（OVA）衍生的SIINFEKL。我们检测到OVA特异性T细胞中的钙通量，是由SIINFEKL肽负载的DC特异性T细胞受体参与触发的。这种方法导致灵敏地检测到抗原特异性钙通量（ACF），低至约10-3uM的肽负载浓度，并且在野生型（WT）中的OT-I细胞频率约为0.1％，无反应细胞。过继转移到对照小鼠体内后，在脾脏，淋巴结和外周血中检测到抗原特异性T细胞。当前在基于免疫疗法的患者（例如ECP）中缺乏用于评估治疗反应的方法，其中通过延迟测量恶性克隆的大小来评估临床反应。这些发现提示了一种早期，实用的方法，可以测量已针对其恶性细胞免疫的ECP治疗患者的治疗诱导的抗肿瘤反应。

BACKGROUND & AIMS: :A replication-competent vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP have shown promise in animals and humans when administered therapeutically. Uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rVSV-ZEBOV vaccinee. Here, we model a worst-case scenario using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. We demonstrate that animals challenged with a uniformly lethal dose of EBOV one day following vaccination, and then treated with the anti-EBOV GP mAb MIL77 starting 3 days postexposure show no evidence of clinical illness and survive challenge. In contrast, animals receiving only vaccination or only mAb-based therapy become ill, with decreased survival compared to animals vaccinated and subsequently treated with MIL77. These results suggest that rVSV-ZEBOV augments immunotherapy.

背景与目标： ：在2013-16年度EBOV流行期间，成功使用了具有复制能力的表达埃博拉病毒（EBOV）糖蛋白（GP）（rVSV-ZEBOV）的水疱性口炎病毒疫苗。此外，针对EBOV GP的嵌合和人类单克隆抗体（mAb）在治疗性给药后在动物和人类中显示出了希望。在已知接触最近的rVSV-ZEBOV疫苗的情况下，有关暴露后抗体治疗功效的不确定性。在这里，我们使用接种rVSV-ZEBOV疫苗或未接种rvsv-zebov疫苗的恒河猴对最坏情况进行建模。我们证明，在接种疫苗后的第一天，用均匀致死剂量的EBOV攻击动物，然后在暴露后3天开始用抗EBOV GP mAb MIL77进行治疗，这些动物均未显示出临床疾病的证据，并且可以在攻击中幸存下来。相反，仅接受疫苗接种或仅接受基于mAb的治疗的动物会生病，与接种疫苗并随后接受MIL77治疗的动物相比，存活率降低。这些结果表明，rVSV-ZEBOV增强了免疫治疗。

BACKGROUND & AIMS: BACKGROUND:There are indications of beneficial short-term effect of pre-operative exercise in reducing pain and improving activity of daily living after total hip replacement (THR) and total knee replacement (TKR) surgery. Though, information from studies conducting longer follow-ups and economic evaluations of exercise prior to THR and TKR is needed. The aim of the study was to analyse 12-month clinical effect and cost-utility of supervised neuromuscular exercise prior to THR and TKR surgery. METHODS:The study was conducted alongside a randomised controlled trial including 165 patients scheduled for standard THR or TKR at a hospital located in a rural area of Denmark. The patients were randomised to replacement surgery with or without an 8-week preoperative supervised neuromuscular exercise program (Clinical Trials registration no.: NCT01003756). Clinical effect was measured with Hip disability and Osteoarthritis Outcome Score (HOOS) and Knee injury and Osteoarthritis Outcome Score (KOOS). Quality adjusted life years (QALYs) were based on EQ-5D-3L and Danish preference weights. Resource use was extracted from national registries and valued using standard tariffs (2012-EUR). Incremental net benefit was analysed to estimate the probability for the intervention being cost effective for a range of threshold values. A health care sector perspective was applied. RESULTS:HOOS/KOOS quality of life [8.25 (95% CI, 0.42 to 16.10)] and QALYs [0.04 (95% CI, 0.01 to 0.07)] were statistically significantly improved. Effect-sizes ranged between 0.09-0.59 for HOOS/KOOS subscales. Despite including an intervention cost of €326 per patient, there was no difference in total cost between groups [€132 (95% CI -3942 to 3679)]. At a threshold of €40,000, preoperative exercise was found to be cost effective at 84% probability. CONCLUSION:Preoperative supervised neuromuscular exercise for 8 weeks was found to be cost-effective in patients scheduled for THR and TKR surgery at conventional thresholds for willingness to pay. One-year clinical effects were small to moderate and favoured the intervention group, but only statistically significant for quality of life measures. TRIAL REGISTRATION:ClinicalTrials.gov ( NCT01003756 ) October 28, 2009.

背景与目标： 背景：有迹象表明，术前短期锻炼有利于减轻疼痛并改善全髋关节置换（THR）和全膝关节置换（TKR）手术后的日常生活活动。但是，需要从进行更长时间的随访研究和在THR和TKR之前对运动进行经济评估的信息。这项研究的目的是分析在THR和TKR手术之前进行有监督的神经肌肉锻炼的12个月临床效果和成本效用。
方法：该研究与一项随机对照试验一起进行，该试验包括165名计划在丹麦农村地区的医院中接受标准THR或TKR治疗的患者。将患者随机分为进行或不进行8周术前有监督的神经肌肉锻炼程序（临床试验注册号：NCT01003756）的替代手术。用髋关节残疾和骨关节炎结果评分（HOOS）以及膝关节损伤和骨关节炎结果评分（KOOS）来衡量临床效果。质量调整生命年（QALYs）基于EQ-5D-3L和丹麦偏好权重。资源使用是从国家注册管理机构中提取的，并使用标准关税（2012-EUR）进行估值。对增量净收益进行了分析，以估计对于一系列阈值而言，干预措施具有成本效益的可能性。应用了卫生保健部门的观点。
结果：HOOS / KOOS生活质量[8.25（95％CI，0.42至16.10）]和QALYs [0.04（95％CI，0.01至0.07）]在统计学上有显着改善。 HOOS / KOOS分量表的效果大小范围在0.09-0.59之间。尽管包括每位患者326欧元的干预费用，但各组之间的总费用没有差异[132欧元（95％CI -3942至3679）]。在术前锻炼的成本阈值为40,000欧元时，发现该锻炼的成本效益为84％。
结论：对于计划进行THR和TKR手术的患者，在常规的支付意愿阈值下，术前进行有监督的8周神经肌肉锻炼是合算的。一年的临床效果小到中等，偏爱干预组，但对生活质量的测量仅具有统计学意义。
试用注册：ClinicalTrials.gov（NCT01003756），2009年10月28日。

BACKGROUND & AIMS: :The interaction of blood and fabrics is currently a 'hot topic', since the understanding and interpretation of these stains is still in its infancy. A recent simplified perpendicular impact experimental programme considering bloodstains generated on fabrics laid the foundations for understanding more complex scenarios. Blood rarely impacts apparel fabrics perpendicular; therefore a systematic study was conducted to characterise the appearance of drip stains on inclined fabrics. The final drip stain appearance for 45° and 15° impact angles on torso apparel fabrics (100% cotton plain woven, 100% polyester plain woven, a blend of polyester and cotton plain woven and 100% cotton single jersey knit) that had been laundered for six, 26 and 52 cycles prior to testing was investigated. The relationship between drop parameters (height and volume), angle and the stain characteristics (parent stain area, axis 1 and 2 and number of satellite stains) for each fabric was examined using analysis of variance. The appearance of the drip stains on these fabrics was distorted, in comparison to drip stains on hard-smooth surface. Examining the parent stain allowed for classification of stains occurring at an angle, however the same could not be said for the satellite stains produced. All of the dried stains visible on the surface of the fabric were larger than just after the impacting event, indicating within fabric spreading of blood due to capillary force (wicking). The cotton-containing fabrics spread the blood within the fabrics in all directions along the stain's circumference, while spreading within the polyester plain woven fabric occurred in only the weft (width of the fabric) and warp (length) directions. Laundering affected the formation of bloodstain on the blend plain woven fabric at both impact angles, although not all characteristics were significantly affected for the three impact conditions considered. The bloodstain characteristics varied due to the fibre content and fabric structure for both impact angles investigated. It is therefore necessary to consider the age of the fabric (which is fabric specific), the fibre type (including blends) and the fabric structure, before interpreting bloodstain patterns. An understanding of this simplified inclined drip stain interaction has been investigated to generate a basis for more complex interactions, such as spatter bloodstains.

背景与目标： ：血液和织物的相互作用目前是一个“热门话题”，因为对这些污渍的理解和解释仍处于起步阶段。最近的一项简化的垂直冲击实验程序考虑了织物上产生的血迹，为理解更复杂的场景奠定了基础。血液很少会垂直影响服装面料。因此进行了系统的研究，以表征倾斜织物上滴落污渍的外观。经过洗涤的躯干服装面料（100％棉平纹织物，100％聚酯平纹织物，聚酯和棉平纹织物的混合物以及100％棉质单面针织物）在45°和15°冲击角下的最终滴落污渍外观在测试前进行了六个，26和52个循环的研究。使用方差分析检查了每种织物的掉落参数（高度和体积），角度和污渍特征（亲代污渍区域，轴1和2和卫星污渍数）之间的关系。与硬光滑表面上的污渍相比，这些织物上的污渍外观失真。检查母体污渍可以对以一定角度出现的污渍进行分类，但是对于产生的卫星污渍却不能说相同。织物表面上可见的所有干燥污渍均比刚刚发生撞击事件后要大，这表明由于毛细作用力（芯吸作用）在织物内散布了血液。含棉织物在血液中沿着污渍的圆周在各个方向上传播血液，而在聚酯平纹织物内的传播仅在纬向（织物的宽度）和经向（长度）方向上发生。尽管在所考虑的三种冲击条件下，并非所有特性都受到显着影响，但洗涤影响了混纺平纹织物上血迹的形成。血迹特性因所研究的两个冲击角的纤维含量和织物结构而异。因此，在解释血迹图案之前，有必要考虑织物的年龄（特定于织物的年龄），纤维类型（包括混纺物）和织物结构。已经研究了对这种简化的倾斜滴液污渍相互作用的理解，从而为更复杂的相互作用（例如飞溅的血迹）奠定了基础。

BACKGROUND & AIMS: BACKGROUND:In product development for lower limb prosthetic devices, a set of special criteria needs to be met. Prosthetic devices have a direct impact on the rehabilitation process after an amputation with both perceived technological and psychological aspects playing an important role. However, available psychometric questionnaires fail to consider the important links between these two dimensions. In this article a probabilistic latent trait model is proposed with seven technical and psychological factors which measure satisfaction with the prosthesis. The results of a first study are used to determine the basic parameters of the statistical model. These distributions represent hypotheses about factor loadings between manifest items and latent factors of the proposed psychometric questionnaire. METHODS:A study was conducted and analyzed to form hypotheses for the prior distributions of the questionnaire's measurement model. An expert agreement study conducted on 22 experts was used to determine the prior distribution of item-factor loadings in the model. RESULTS:Model parameters that had to be specified as part of the measurement model were informed prior distributions on the item-factor loadings. For the current 70 items in the questionnaire, each factor loading was set to represent the certainty with which experts had assigned the items to their respective factors. Considering only the measurement model and not the structural model of the questionnaire, 70 out of 217 informed prior distributions on parameters were set. CONCLUSION:The use of preliminary studies to set prior distributions in latent trait models, while being a relatively new approach in psychological research, provides helpful information towards the design of a seven factor questionnaire that means to identify relations between technical and psychological factors in prosthetic product design and rehabilitation medicine.

背景与目标： 背景：在下肢假体产品开发中，需要满足一组特殊标准。假肢在截肢后对康复过程有直接影响，感知的技术和心理方面都起着重要的作用。但是，可用的心理测量问卷无法考虑这两个维度之间的重要联系。本文提出了一种概率潜在特征模型，该模型具有七个技术和心理因素来衡量对假体的满意度。首次研究的结果用于确定统计模型的基本参数。这些分布表示有关拟议的心理测验问卷的清单项目和潜在因素之间的因素负荷的假设。
方法：进行了一项研究并进行了分析，以形成问卷调查模型的先前分布的假设。对22位专家进行的专家协议研究用于确定模型中项目因子负荷的先前分布。
结果：必须将作为测量模型一部分指定的模型参数告知项目因子负荷的先前分布。对于问卷中当前的70个项目，设置每个因素负荷以表示专家将项目分配给其各自因素的确定性。仅考虑测量模型而不考虑问卷的结构模型，在217个已知的参数先验分布中设置了70个。
结论：使用初步研究来设定潜在性状模型中的先验分布，虽然是心理学研究中的一种相对较新的方法，但为设计七因子问卷提供了有用的信息，该问卷旨在识别假肢产品中技术和心理因素之间的关系。设计和康复医学。

BACKGROUND & AIMS: PURPOSE:Minimally invasive parathyroidectomy (MIP) is the recommended treatment in primary hyperparathyroidism (pHPT) for which accurate preoperative localization is essential. The current imaging standard consists of cervical ultrasonography (cUS) and MIBI-SPECT/CT. 11C-MET PET/CT has a higher resolution than MIBI-SPECT/CT. The aim of this study was to determine the diagnostic performance of 11C-MET PET/CT after initial inconclusive or negative localization. METHODS:We performed a retrospective single center cohort study of patients with pHPT undergoing parathyroid surgery after prior negative imaging and later localization by means of 11C-MET PET/CT between 2006 and 2014. Preoperative localization by 11C-MET PET/CT was compared with later surgical localization, intraoperative quick PTH (IOPTH), duration of surgery, histopathology, and follow-up data. Also, differences in duration of surgery between the groups with and without correct preoperative localization were analyzed. RESULTS:In 18/28 included patients a positive 11C-MET-PET/CT result corresponded to the surgical localized adenoma (64%). In 3/28 patients imaging was false positive and no adenoma was found. In 7/28 patients imaging was false negative at the side of the surgically identified adenoma. Sensitivity of 11C-MET PET/CT was 72% (18/25). Duration of surgery of correctly localized patients was significantly shorter compared to falsely negative localized patients (p = 0.045). CONCLUSION:In an intention to treat 11C-MET-PET/CT correctly localized the parathyroid adenoma in 18/28 (64%) patients, after previous negative imaging. A preoperatively correct localized adenoma leads to a more focused surgical approach (MIP) potentially reducing duration of surgery and potentially healthcare costs.

背景与目标： 目的：微创甲状旁腺切除术（MIP）是原发性甲状旁腺功能亢进症（pHPT）的推荐治疗方法，因此准确的术前定位至关重要。当前的成像标准包括宫颈超声检查（cUS）和MIBI-SPECT / CT。 11C-MET PET / CT具有比MIBI-SPECT / CT更高的分辨率。这项研究的目的是确定最初的不确定性或阴性定位后的11C-MET PET / CT的诊断性能。
方法：我们对2006年至2014年间先有阴性影像学检查，后来通过11C-MET PET / CT定位的甲状旁腺癌患者进行了甲状旁腺手术的回顾性单中心队列研究。将11C-MET PET / CT的术前定位与稍后的手术定位，术中快速PTH（IOPTH），手术时间，组织病理学和随访数据。此外，分析了有无正确术前定位的两组之间的手术时间差异。
结果：在18/28名患者中，11C-MET-PET / CT阳性结果与手术局部腺瘤相对应（64％）。在3/28位患者中，影像学检查为假阳性，未发现腺瘤。在7/28例患者中，经手术鉴定出的腺瘤一侧的影像学检查为假阴性。 11C-MET PET / CT的灵敏度为72％（18/25）。与假阴性的局部患者相比，正确定位的患者的手术时间显着缩短（p = 0.045）。
结论：为治疗11C-MET-PET / CT，在先前的阴性影像后，正确定位了18/28（64％）患者的甲状旁腺腺瘤。术前正确的局部腺瘤可导致更集中的手术方法（MIP），从而可能减少手术时间并降低医疗成本。

BACKGROUND & AIMS: :Thresholds were measured for 5-ms 1-kHz tones masked by synchronous bursts of noise containing a spectral notch centered on the signal frequency. Thresholds were reduced by prior exposure to a 200-ms burst of a 'priming stimulus' which had the same spectral shape as the masker. The masking release was greatest for notch widths extending between 20-30% above and below the signal frequency. It did not occur when the masker and primer were bandpass noises extending from 200-1800 Hz. A smaller masking release could be obtained with a primer consisting of only the lower band of a notched noise masker. This was also true, but to a lesser extent, for a primer consisting of the higher band alone. A primer that was a narrow band of noise centered on the signal frequency produced an increase in masking, which could not be attributed to forward masking of the tone by the primer. The effects of all primers were independent of primer level over the 30-dB range studied, ruling out explanations in terms of peripheral adaptation or of adaptation of suppression. A significant masking release occurred when the silent interval between primer offset and masker onset was as long as 320 ms, but increasing the duration of the masker and signal beyond 80 ms eliminated the effect in two out of three subjects. The results are consistent with a form of processing which groups together energy in frequency regions containing common amplitude envelopes, and which enhances the internal representation of newly-arriving energy in previously unstimulated frequency regions.

背景与目标： ：对阈值进行了5ms 1-kHz音调的测量，这些音调被同步的噪声突发所掩盖，噪声中包含以信号频率为中心的频谱陷波。通过事先暴露于200毫秒的“起爆刺激”中，可以降低阈值，该“起爆刺激”具有与掩膜相同的频谱形状。对于在信号频率之上和之下20-30％之间延伸的陷波宽度，屏蔽释放最大。当掩蔽剂和底漆为200-1800 Hz的带通噪声时，不会发生这种情况。用仅由带切口的噪声掩蔽器的下部带组成的底漆可以获得较小的掩蔽释放。对于仅由较高条带组成的引物，也是如此，但程度较小。以信号频率为中心的窄带噪声的底漆会导致掩蔽的增加，这不能归因于底漆对音调的正向掩蔽。在研究的30 dB范围内，所有引物的作用均与引物水平无关，从而排除了对周围适应或抑制适应的解释。当引物偏移量与掩蔽剂发作之间的沉默间隔长达320 ms时，发生了显着的掩蔽释放，但是增加掩蔽剂的持续时间和信号超过80 ms消除了三分之二的受试者的影响。结果与一种处理形式相符，该处理将包含共同幅度包络的频率区域中的能量分组在一起，并且增强了以前未受刺激的频率区域中新到达能量的内部表示。