BACKGROUND & AIMS: :The goal of this study was to establish and validate a protocol for preparing bovine cardiomyocytes from slaughterhouse material for nuclear transfer experiments. The cardiomyocyte was selected because it is a terminally differentiated cell and strongly expresses a unique subset of genes which can be monitored during the reprogramming period. A total of 39 trials were conducted, and an optimized protocol was developed yielding individual contractile cardiomyocytes from 3-5-month-old bovine fetuses The basic protocol involves stabilization of bovine heart tissue for transportation from the slaughterhouse to the laboratory by perfusion with Custodiol. This was followed by an enzymatic dissociation with collagenase in calcium-free medium and yielded individual contractile rod-shaped cardiomyocytes. Subsequent addition of Ca2+ caused the cardiomyocytes to round up which was an essential pre-condition for drawing them into glass transfer pipettes for delivery into the perivitelline space and for efficient electrofusion with cytoplasts derived from in vitro matured bovine oocytes. The use of cardiomyocytes maintained at 37 degrees C in nuclear transfer, resulted in a significantly reduced proportion of blastocysts compared to adult fibroblasts (14.0% versus 32.7%). Storage of cardiomyocytes at 4 degrees C prior to nuclear transfer was not compatible with blastocyst development. It is expected that this system will be valuable for investigating the reprogramming of gene expression which occurs after somatic cell nuclear transfer.

背景与目标： ：这项研究的目的是建立和验证从屠宰场材料制备牛心肌细胞用于核移植实验的方案。选择心肌细胞是因为它是终末分化细胞，并且强烈表达可以在重编程期间监测的独特基因子集。总共进行了39次试验，并开发了优化的方案，以从3-5个月大的牛胎儿中产生单个可收缩的心肌细胞。基本方案涉及稳定牛心脏组织，以便通过灌注邻苯二酚从屠宰场运至实验室。然后在无钙培养基中用胶原酶进行酶解，产生单个可收缩的杆状心肌细胞。随后添加的Ca2导致心肌细胞聚集，这是将它们吸引到玻璃移液管中以输送到玻璃体腔中并与源自体外成熟牛卵母细胞的细胞质进行有效电融合的必要先决条件。与成年成纤维细胞相比，使用维持在37摄氏度的心肌细胞进行核移植，导致胚泡的比例大大降低（分别为14.0％和32.7％）。核移植前将心肌细胞储存在4摄氏度下与胚泡发育不兼容。预期该系统对于研究在体细胞核转移后发生的基因表达的重编程将是有价值的。

BACKGROUND & AIMS: :We have proposed a transdermal biolistic method to accelerate a powder formulation of drugs to penetrate human skin for the treatment of a range of diseases. One of the key issues for designing and evaluating transdermal biolistic system is ensuing that the powder drugs are delivered into the skin with a controllable velocity range and spatial distribution. The aerodynamics of supersonic nozzles and performance of the delivery system were initially studied, mainly analytically and experimentally. In this paper, computational fluid dynamics is utilized to characterize two existing prototype devices, in order to further investigate the transient gas and particle dynamics in their supersonic nozzles. To validate the implemented numerical approach, calculated pressure histories, two-dimensional flow structures and particle velocity distributions are made and compared with the reported experimental measurements. The key features of gas dynamics, gas-particle interaction and performance of the prototype transdermal biolistics are discussed and interpreted.

背景与目标： ：我们提出了一种透皮生物弹射法，以加快药物粉末制剂的渗透，从而渗透到人类皮肤中，以治疗多种疾病。设计和评估透皮生物弹药系统的关键问题之一是确保将粉末药物以可控制的速度范围和空间分布传递到皮肤中。最初主要是通过分析和实验研究超音速喷嘴的空气动力学和输送系统的性能。在本文中，利用计算流体动力学来表征两个现有的原型设备，以进一步研究其超音速喷嘴中的瞬态气体和粒子动力学。为了验证已实施的数值方法，计算了压力历史，二维流动结构和颗粒速度分布，并将其与报告的实验测量结果进行了比较。讨论并解释了气体动力学，气体-颗粒相互作用和原型透皮生物弹性能的关键特征。

BACKGROUND & AIMS: AIMS:Case reports suggest an interaction between rofecoxib and the CYP1A2 substrate tizanidine. Our objectives were to explore the extent and mechanism of this possible interaction and to determine the CYP1A2 inhibitory potency of rofecoxib. METHODS:In a randomized, double-blind, two-phase cross-over study, nine healthy subjects took 25 mg rofecoxib or placebo daily for 4 days and, on day 4, each ingested 4 mg tizanidine. Plasma concentrations and the urinary excretion of tizanidine, its metabolites (M) and rofecoxib, and pharmacodynamic variables were measured up to 24 h. On day 3, a caffeine test was performed to estimate CYP1A2 activity. RESULTS:Rofecoxib increased the area under the plasma concentration-time curve (AUC(0-infinity)) of tizanidine by 13.6-fold [95% confidence interval (CI) 8.0, 15.6; P < 0.001), peak plasma concentration (C(max)) by 6.1-fold (4.8, 7.3; P < 0.001) and elimination half-life (t(1/2)) from 1.6 to 3.0 h (P < 0.001). Consequently, rofecoxib markedly increased the blood pressure-lowering and sedative effects of tizanidine (P < 0.05). Rofecoxib increased several fold the tizanidine/M-3 and tizanidine/M-4 ratios in plasma and urine and the tizanidine/M-5, tizanidine/M-9 and tizanidine/M-10 ratios in urine (P < 0.05). In addition, it increased the plasma caffeine/paraxanthine ratio by 2.4-fold (95% CI 1.4, 3.4; P = 0.008) and this ratio correlated with the tizanidine/metabolite ratios. Finally, the AUC(0-25) of rofecoxib correlated with the placebo phase caffeine/paraxanthine ratio (r = 0.80, P = 0.01). CONCLUSIONS:Rofecoxib is a potent inhibitor of CYP1A2 and it greatly increases the plasma concentrations and adverse effects of tizanidine. The findings suggest that rofecoxib itself is also metabolized by CYP1A2, raising concerns about interactions between rofecoxib and other CYP1A2 substrate and inhibitor drugs.

背景与目标： 目的：病例报告表明罗非考昔与CYP1A2底物替扎尼定之间存在相互作用。我们的目标是探索这种可能的相互作用的程度和机制，并确定罗非昔布对CYP1A2的抑制作用。
方法：在一项随机，双盲，两阶段交叉研究中，九名健康受试者每天服用25毫克罗非考昔或安慰剂，持续4天，并在第4天，每人摄入4毫克替扎尼定。在长达24小时内测量替扎尼定，其代谢产物（M）和罗非考昔的血浆浓度和尿排泄，以及药效学变量。在第3天，进行了咖啡因测试以评估CYP1A2的活性。
结果：罗非昔布将替扎尼定的血浆浓度-时间曲线下面积（AUC（0-无穷大））增加了13.6倍[95％置信区间（CI）8.0、15.6； P <0.001），峰值血药浓度（C（max））从1.6到3.0 h的6.1倍（4.8，7.3; P <0.001）和消除半衰期（t（1/2））（P <0.001） 。因此，罗非昔布显着增强了替扎尼定的降压和镇静作用（P <0.05）。罗非昔布将血浆和尿液中替扎尼定/ M-3和替扎尼定/ M-4的比例提高了几倍，尿液中替扎尼定/ M-5，替扎尼定/ M-9和替扎尼定/ M-10的比例提高了几倍（P <0.05）。此外，它使血浆咖啡因/对黄嘌呤比率增加了2.4倍（95％CI 1.4、3.4； P = 0.008），并且该比率与替扎尼定/代谢产物比率相关。最后，罗非昔布的AUC（0-25）与安慰剂相咖啡因/对黄嘌呤的比​​例相关（r = 0.80，P = 0.01）。
结论：罗非昔布是一种有效的CYP1A2抑制剂，它大大提高了血浆浓度和替扎尼定的不良反应。研究结果表明罗非考昔本身也被CYP1A2代谢，引起对罗非考昔与其他CYP1A2底物和抑制剂药物之间相互作用的担忧。

BACKGROUND & AIMS: :In stock enhancement programs, it is important to assess mixing rates of released individuals in stocks. For this purpose, genetic stock identification has been applied. The allele frequencies in a composite population are expressed as a mixture of the allele frequencies in the natural and released populations. The estimation of mixing rates is possible, under successive sampling from the composite population, on the basis of temporal changes in allele frequencies. The allele frequencies in the natural population may be estimated from those of the composite population in the preceding year. However, it should be noted that these frequencies can vary between generations due to genetic drift. In this article, we develop a new method for simultaneous estimation of mixing rates and genetic drift in a stock enhancement program. Numerical simulation shows that our procedure estimates the mixing rate with little bias. Although the genetic drift is underestimated when the amount of information is small, reduction of the bias is possible by analyzing multiple unlinked loci. The method was applied to real data on mud crab stocking, and the result showed a yearly variation in the mixing rate.

背景与目标： ：在库存增强计划中，评估库存中已释放人员的混合比率很重要。为此，已应用遗传种群鉴定。复合种群中的等位基因频率表示为自然种群和释放种群中等位基因频率的混合。在等位基因频率的时间变化的基础上，在连续采样下从复合种群中估计混合速率是可能的。天然种群中的等位基因频率可以根据前一年的复合种群的等位基因频率进行估算。但是，应注意的是，由于遗传漂移，这些频率在世代之间可能会有所不同。在本文中，我们开发了一种新的方法，可同时估算种群增强程序中的混合速率和遗传漂移。数值模拟表明，我们的方法估计的混合速率几乎没有偏差。尽管当信息量小时，遗传漂移会被低估，但通过分析多个未连锁的基因座可以降低偏倚。该方法应用于泥蟹放养的真实数据，结果表明混合速率逐年变化。

BACKGROUND & AIMS: :The distributed genome hypothesis (DGH) states that each strain within a bacterial species receives a unique distribution of genes from a population-based supragenome that is many times larger than the genome of any given strain. The observations that natural infecting populations are often polyclonal and that most chronic bacterial pathogens have highly developed mechanisms for horizontal gene transfer suggested the DGH and provided the means and the mechanisms to explain how chronic infections persist in the face of a mammalian host's adaptive defense mechanisms. Having previously established the validity of the DGH for obligate pathogens, we wished to evaluate its applicability to an opportunistic bacterial pathogen. This was accomplished by construction and analysis of a highly redundant pooled genomic library containing approximately 216,000 functional clones that was constructed from 12 low-passage clinical isolates of Pseudomonas aeruginosa, 6 otorrheic isolates and 6 from other body sites. Sequence analysis of 3,214 randomly picked clones (mean insert size, approximately 1.4 kb) from this library demonstrated that 348 (10.8%) of the clones were unique with respect to all genomic sequences of the P. aeruginosa prototype strain, PAO1. Hypothetical translations of the open reading frames within these unique sequences demonstrated protein homologies to a number of bacterial virulence factors and other proteins not previously identified in P. aeruginosa. PCR and reverse transcription-PCR-based assays were performed to analyze the distribution and expression patterns of a 70-open reading frame subset of these sequences among 11 of the clinical strains. These sequences were unevenly distributed among the clinical isolates, with nearly half (34/70) of the novel sequences being present in only one or two of the individual strains. Expression profiling revealed that a vast majority of these sequences are expressed, strongly suggesting they encode functional proteins.

背景与目标： ：分布式基因组假设（DGH）指出，细菌物种中的每个菌株都从基于种群的超基因组中获得独特的基因分布，其比任何给定菌株的基因组都要大很多倍。自然感染人群通常是多克隆的，大多数慢性细菌病原体具有高度发展的水平基因转移机制的观察结果提示了DGH，并提供了解释哺乳动物宿主面对适应性防御机制时慢性感染如何持续存在的手段和机制。先前已确定DGH对专性病原体的有效性，我们希望评估其对机会细菌病原体的适用性。这是通过构建和分析包含约216,000个功能性克隆的高度冗余的集合基因组文库完成的，该文库由铜绿假单胞菌的12种低通道临床分离株，6种耳泻分离株和6个其他身体部位构建而成。对来自该文库的3,214个随机挑选的克隆（平均插入片段大小，约1.4 kb）进行序列分析，结果表明，对于铜绿假单胞菌原型菌株PAO1的所有基因组序列，其中348个（10.8％）克隆是唯一的。在这些独特序列内的开放阅读框的假想翻译证明了与许多细菌毒力因子和以前在铜绿假单胞菌中未鉴定出的其他蛋白质的蛋白质同源性。进行了基于PCR和逆转录PCR的分析，以分析这些序列的70个开放阅读框子集在11种临床菌株中的分布和表达模式。这些序列在临床分离株中分布不均，只有一半或34个新序列出现在一个或两个单独的菌株中。表达谱分析表明这些序列中的绝大多数都被表达，强烈暗示它们编码功能蛋白。

BACKGROUND & AIMS: AIM:This paper reviews how the interpreter's role is described in empirically based, qualitative cross-cultural interview studies and how trustworthiness is determined. BACKGROUND:Increased immigration during the past decades has created a multiethnic society in many countries. This development poses a challenge to healthcare staff, in that they need to understand how people from different cultures experience health and illness. One way to assess immigrants' experiences is through cross-cultural interview studies, involving an interpreter. Thorough knowledge of the interpreter's role is needed in order to increase the trustworthiness of this kind of nursing research. METHOD:Literature searches were conducted from October to November 2004 using PubMed, CINAHL, Psycinfo, Sociological abstract, Your Journals@ovid, and Eric databases. Qualitative interview studies written in English and performed with an interpreter were included. The Matrix Method was used to review the literature. FINDINGS:In almost all of the 13 relevant papers found, the role of the interpreter(s) in the research process was only sparsely described. In addition, all studies except one employed different techniques to established trustworthiness. The most common techniques were prolonged engagement, member check or triangulation, the latter performed either on the data, investigators or methods. CONCLUSION:Methodological issues with respect to interpreters have received only limited attention in cross-cultural interview studies. Researchers in the field of nursing need to consider (1) the interpreter's role/involvement in the research process; (2) the interpreter's competence and the style of interpreting; (3) the interpreter's impact on the findings. This information is a prerequisite when trying to determine the trustworthiness of a cross-cultural study.

背景与目标： 目的：本文回顾了如何在基于经验的定性跨文化访谈研究中描述口译员的角色，以及如何确定信任度。
背景：过去几十年来移民的增加在许多国家创建了一个多种族的社会。这种发展对医护人员提出了挑战，因为他们需要了解来自不同文化背景的人们如何经历健康和疾病。评估移民经验的一种方法是通过跨文化访谈研究，其中包括一名口译员。为了增加这种护理研究的可信度，需要对口译员的作用有透彻的了解。
方法：从2004年10月至2004年11月使用PubMed，CINAHL，Psycinfo，Sociological abstract，Your Journals @ ovid和Eric数据库进行文献检索。包括用英语撰写并由口译员进行的定性访谈研究。矩阵法用于回顾文献。
结果：在发现的所有13篇相关论文中，几乎都很少描述口译员在研究过程中的作用。此外，除一项研究外，所有研究均采用不同的技术来建立可信度。最常见的技术是长时间的接触，成员检查或三角剖分，后者根据数据，研究人员或方法进行。
结论：关于口译员的方法论问题在跨文化访谈研究中仅受到了有限的关注。护理领域的研究人员需要考虑（1）口译员在研究过程中的角色/参与程度； （二）口译人员的能力和口译风格； （3）口译员对调查结果的影响。在尝试确定跨文化研究的可信赖性时，此信息是前提条件。

BACKGROUND & AIMS: BACKGROUND:Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. RESULTS:We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CONCLUSION:CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.

背景与目标： 背景：目前的基因组研究方法为研究人员提供了大量数据。结合生物学数据库中常用的不同高通量研究技术的数据，可以得出新颖的发现并提高研究效率。但是，合并来自不同异构源的数据通常是一项艰巨的任务。这些来源可以是不同的微阵列技术平台，基因组数据库或对各种物种进行的实验。我们的目标是开发一个软件程序，以方便来自不同来源的数据的合并，从而使研究人员能够进行基因组跨平台/跨物种研究，并将现有的实验数据用于纲要研究。
结果：我们开发了一个基于Web的软件资源，称为CROPPER，该资源使用有关Ensembl数据库中不同数据标识符和直系同源基因的最新基因组信息。 CROPPER可用于组合来自不同异构来源的基因组数据，从而使研究人员无需复杂的计算工具或建立自己的内部数据库即可进行跨平台/跨物种纲要研究。我们还提供了一个简单的跨平台/跨物种纲要研究的例子，该研究基于从不同来源获得的公开可用的帕金森氏病数据。
结论：CROPPER是一种用户友好且免费提供的基于Web的软件资源，可以成功地用于跨物种/跨平台纲要研究。

BACKGROUND & AIMS: Previous mutagenesis studies with bacteriorhodopsin have shown that reprotonation of the Schiff's base is the rate-limiting step in the photocycle of the D96N mutant, whereas retinal re-isomerization and return of the protein to the initial state constitute the rate-limiting events in the photocycle of the L93A mutant. Thus, in the D96N mutant, decay of the M intermediate is slowed down by more than 100-fold at pH 7. In the L93A mutant, decay of the O intermediate is slowed down by 250-fold. We report here that in the L93A, D96N double mutant, decay of the M intermediate, as well as the formation and decay of the O intermediate, are slowed down dramatically. The photocycle is completed by the decay of a long-lived O intermediate, as in the L93A mutant. The decay of the M and O intermediates in the double mutant parallels the behavior seen in the single mutants over a wide temperature and pH range, arguing that the observed independence is an intrinsic property of the mutant. The slow decay of the M and O intermediates can be selectively and independently reversed under conditions identical to those used for the corresponding intermediates in the D96N and L93A single mutants. Because the effects of the two individual mutations are preserved in the double mutant and can be independently reversed, we conclude that residues Asp 96 and Leu 93 act independently and at different stages of the bacteriorhodopsin photocycle. These results also show that formation of the O intermediate only requires protonation of the Schiff's base and is independent of the protonation of Asp 96 from the aqueous medium.

背景与目标： 先前使用细菌视紫红质的诱变研究表明，席夫氏碱的质子化是D96N突变体光循环中的限速步骤，而视网膜重新异构化和蛋白质返回初始状态构成了光循环中的限速事件L93A突变体的序列。因此，在D96N突变体中，在pH 7时，M中间体的衰减减慢了100倍以上。在L93A突变体中，O中间体的衰减减慢了250倍。我们在这里报告说，在L93A，D96N双突变体中，M中间物的衰减以及O中间物的形成和衰减都大大减慢了。像L93A突变体一样，光循环是通过长寿命的O中间体的降解来完成的。双重突变体中M和O中间体的衰变与单个突变体在较宽的温度和pH范围内观察到的行为相似，认为观察到的独立性是突变体的固有特性。 M和O中间体的缓慢衰变可以在与D96N和L93A单突变体中相应中间体相同的条件下有选择地独立逆转。因为两个突变体的作用保留在双突变体中并且可以独立逆转，所以我们得出结论，残基Asp 96和Leu 93分别在细菌视紫红质光循环的不同阶段起作用。这些结果还表明，O中间体的形成仅需要席夫碱的质子化，而与来自水性介质的Asp 96的质子化无关。

BACKGROUND & AIMS: PURPOSE:To determine the clinical importance and relative value of reinterpreting brain CT imaging studies by subspecialty experts regarding changes in clinical management. METHODS:Computerized records were queried at two institutions during the years 2002-2003 for both primary interpretation by board-certified nonneuroradiologists and secondary interpretation by three neuroradiologists. A total of 1,081 cases were reviewed. Each case was initially interpreted as an emergent or urgent study. The reinterpreted studies were scored as concordant or discordant by the subspecialty experts. The discordant studies were then categorized as a "major discordance" if there was a change in clinical management, or as a "minor discordance" if there was no impact or change in clinical management. RESULTS:Of the 1,081 studies reviewed, 14 studies were identified as discordant (1.3%). Of those discordant studies, four were categorized as major discrepancies necessitating a change in clinical management (0.4 %). Ten were categorized as minor discrepancies (0.9%). There were no permanent adverse outcomes with respect to morbidity and mortality as a result of any discrepancy. CONCLUSION:The vast majority of interpreted head CT cases read by board-certified general radiologists do not result in discordant interpretations as verified by subspecialty experts. Discordant interpretations did not result in changes in clinical management in most cases. Double reading of head CTs by subspecialty experts appears to be an inefficient method of substantially improving imaging health quality outcomes.

背景与目标： 目的：确定亚专业专家对临床管理变化进行重新解释的脑部CT成像研究的临床重要性和相对价值。
方法：在2002年至2003年期间，在两家机构中查询了计算机记录，以获取由董事会认证的非神经放射科医生进行的主要解释，以及由三位神经放射科医生进行的次要解释。总共审查了1,081例。最初，每个案例都被解释为紧急研究。重新解释的研究被专业专家评定为一致或不一致。如果临床管理发生变化，则将不一致的研究分类为“重大不一致”，如果临床管理没有影响或发生变化，则将其分类为“较小不一致”。
结果：在所审查的1,081项研究中，有14项研究被确定为不一致（1.3％）。在这些不一致的研究中，有四项被归类为需要改变临床管理的主要差异（0.4％）。十个分类为轻微差异（0.9％）。任何差异都不会在发病率和死亡率方面带来永久性的不良后果。
结论：经董事会认证的一般放射科医生阅读的绝大多数解释性头部CT病例，经专科专家验证，并不会导致不一致的解释。在大多数情况下，不一致的解释并不会导致临床管理的改变。专科专家对头颅CT进行双重读取似乎是一种实质上改善影像健康质量结果的无效方法。

BACKGROUND & AIMS: :In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas® HPV Test, Roche®, HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.

背景与目标： ：在本项初步研究中，对希腊北部农村地区服务水平低下的346名妇女进行了基于宫颈癌阴道自我采样方法的HPV筛查的可行性的测试。这些妇女提供了自己收集的宫颈阴道样本以及研究问卷。在进行分子测试后，使用cobas®HPV测试，将Roche®，HPV阳性女性进行阴道镜检查，并在发现异常后进行活检和治疗。参与率为100％。定期进行巴氏试验检查的报道为17.1％。在hrHPV测试中，有11.9％呈阳性，阴道镜检查/活检显示有2例CIN3病例。不遵守是没有参加会议的最普遍原因。大多数妇女在自我抽样中报告没有困难和不舒服（分别为77.6％和82.4％）。他们将选择自采样而不是临床医生采样（86.2％），并且如果可以使用自采样，他们将更定期地进行自我测试（92.3％）。总之，对于基于HPV的筛查，自我抽样是可行的并且被广泛接受，并且可以扩大服务不足地区的人口覆盖率，有助于成功进行预防。

BACKGROUND & AIMS: :Extensive laboratory testing is often performed in the emergency department evaluation of the new-onset seizure patient. To determine the utility of such testing, a prospective study of patients with a new-onset seizure presenting to the ED of an inner-city, university-affiliated teaching hospital was done. One hundred thirty-six patients were entered into the study between October 1984 and January 1988. All patients had uniform data collection performed. Pertinent historical information and physical examination findings were recorded on a standardized form before laboratory abnormality was a sole or contributory cause of the seizure disorder. These included four patients with hypoglycemia, four with hyperglycemia, two with hypocalcemia, and one with hypomagnesemia. Only two cases (hypoglycemia) were not suspected on the basis of findings on the history or physical examination. In ED patients, the incidence of a new-onset seizure due to a correctable metabolic disturbance is low. We conclude that, with the exception of the serum glucose, the extensive ED laboratory workup often done for the evaluation of a new-onset seizure is unnecessary. Further test ordering should be directed by the medical history and physical examination.

背景与目标： ：急诊科通常会对新发作的癫痫患者进行广泛的实验室检查。为了确定此类测试的实用性，对在市内大学附属教学医院急诊室就诊的新发癫痫患者进行了一项前瞻性研究。在1984年10月至1988年1月之间，共有136例患者进入研究。所有患者均进行了统一的数据收集。在实验室异常是癫痫发作的唯一或共同原因之前，以标准化的形式记录相关的历史信息和体格检查结果。这些患者包括四名低血糖患者，四名高血糖患者，两名低钙血症患者和一名低镁血症患者。根据病史或体格检查的结果，仅怀疑2例（低血糖）。在ED患者中，由于可纠正的代谢紊乱引起的新发作癫痫发作的发生率较低。我们得出的结论是，除血清葡萄糖外，不必要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的测试顺序应由病史和体格检查指示。

BACKGROUND & AIMS: AIM:To report the patterns and sites of 18-FDG uptake in patients of presumed ocular tuberculosis. MATERIALS AND METHODS:The clinical and investigational findings of 11 patients were reviewed retrospectively. These included 6 males and 5 females with a mean age of 46.2 years. 21 eyes were included in the data analysis. Clinical presentations include 15 eyes with anterior uveitis, 2 eyes with retinal vasculitis, 2 eyes with panuveitis and 2 eyes with multifocal choroidopathy. RESULTS:Two distinct patterns of systemic uptake emerged. Pattern 1: No detectable systemic uptake (4 patients). Pattern 2: Detectable systemic uptake. a. Chest disease only (2 patients). b. Disseminated pattern, uptake seen at multiple sites (4 patients). c. Extrapulmonary only (1 patient). CONCLUSIONS:Ocular tuberculosis may often be part of a wider disseminated disease.

背景与目标： 目的：报告推测的眼结核患者摄取18-FDG的方式和部位。
材料与方法：回顾性分析11例患者的临床和研究结果。其中包括6名男性和5名女性，平均年龄为46.2岁。数据分析包括21只眼睛。临床表现包括前葡萄膜炎15眼，视网膜血管炎2眼，胰腺炎2眼和多灶性脉络膜病变2眼。
结果：出现了两种不同的全身吸收模式。模式1：未检测到全身吸收（4例患者）。模式2：可检测到的全身吸收。一种。仅胸部疾病（2例）。 b。分布模式，在多个部位可见吸收（4例）。 C。仅肺外（1例患者）。
结论：眼结核通常可能是更广泛传播的疾病的一部分。

BACKGROUND & AIMS: :T cell regulation of the generation of thyroglobulin plaque-forming cells (Tg PFC) and protein A plaque-forming cells (Prot A PFC) was investigated using lymphocytes from patients with autoimmune thyroid disease. T and B cell mixed cultures (T-B MC) were carried out without mitogenic or antigenic stimulation to identify physiological T cell effects in the system. Tg PFC were found in 8 (44%) of 18 patients who had high titers of thyroglobulin antibody in their sera. Tg-specific and nonspecific immunoregulation by T cells from patients and normal subjects was studied using B cells from these eight patients in the T-B MC system. Remarkably lower values of Tg PFC induction compared to Prot A PFC induction were found after T cell addition. Normal T cells inhibited Tg PFC induction, but patient T cells did not, while the same extent of helper effects were found on Prot A PFC induction by the addition of patient and normal T cells. Irradiation (1500 rads) of T cells from patients and normal subjects significantly enhanced both TgPFC and Prot A PFC induction. Thus, Tg-specific suppressor T cells are present in all normal subjects as part of the radiosensitive suppressor T cell subset. The increase in Tg-PFC caused by irradiation-induced inhibition of Tg-specific suppressor T cell function was significantly greater in normal subjects than in patients. Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system. No Tg PFC were induced from normal B cells in any combination with untreated T cells, irradiated T cells, or histamine type 2 receptor-negative T cells from patients or normal subjects. These data indicate that in vitro Tg-specific T cell regulation can be studied in the T-B MC system by using B cells from patients with autoimmune thyroid disease with high Tg antibody titers in their sera. Tg-specific suppressor T cells appear to be present in all individuals and to be involved in the regulation of Tg antibody production. The lower activity of Tg-specific suppressor T cells in patients compared to that in normal subjects may be related to Tg antibody production in vivo. This abnormality, however, is heterogeneous and is not a complete but, rather, is a relative defect of Tg-specific suppressor T cells.

背景与目标： ：使用自身免疫性甲状腺疾病患者的淋巴细胞研究了甲状腺球蛋白斑块形成细胞（Tg PFC）和蛋白A斑块形成细胞（Prot A PFC）生成的T细胞调节。在无有丝分裂或抗原刺激的情况下进行T细胞和B细胞混合培养（T-B MC），以鉴定系统中的生理性T细胞效应。在血清中滴度高的甲状腺球蛋白抗体的18例患者中，有8例（44％）发现了Tg PFC。使用来自这八名患者的B细胞在T-B MC系统中研究了来自患者和正常受试者的T细胞的Tg特异性和非特异性免疫调节。在添加T细胞后，发现Tg PFC诱导的值比Prot A PFC诱导的低得多。正常T细胞抑制Tg PFC诱导，但对患者T细胞没有抑制作用，而通过添加患者和正常T细胞对Prot A PFC诱导发现了相同程度的辅助作用。患者和正常受试者的T细胞辐射（1500 rads）显着增强了TgPFC和Prot A PFC的诱导作用。因此，Tg特异性抑制T细胞作为放射抑制性T细胞亚群的一部分存在于所有正常受试者中。由辐射诱导的Tg特异性抑制T细胞功能的抑制引起的Tg-PFC的增加在正常受试者中比在患者中显着更大。在自体T-B MC系统中，带有组胺2型受体的T细胞抑制Prot A PFC诱导，但不抑制Tg PFC诱导。正常B细胞​​与未经治疗的T细胞，经辐照的T细胞或来自患者或正常受试者的组胺2型受体阴性T细胞的任何组合均未诱导Tg PFC。这些数据表明，可以通过使用来自自身免疫性甲状腺疾病患者血清中Tg抗体滴度高的患者的B细胞，在T-B MC系统中研究体外Tg特异性T细胞调节。 Tg特异性抑制性T细胞似乎存在于所有个体中，并参与Tg抗体产生的调节。与正常受试者相比，患者中Tg特异性抑制性T细胞的活性较低可能与体内Tg抗体的产生有关。然而，这种异常是异质的，不是完全的，而是Tg特异性抑制性T细胞的相对缺陷。

BACKGROUND & AIMS: BACKGROUND:There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. METHODS:In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. RESULTS:We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. CONCLUSIONS:We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally, a simulation should be based on real data for adequately reflecting complex observational data structures, such as found in epidemiological cohort studies.

背景与目标： 背景技术：越来越多的观察性研究不仅专注于单个生物标志物来预测结果事件，而且在多变量环境中解决问题。例如，当量化除已建立的风险因素外的新生物标记物的附加值时，目标可能是就其预测性能对几种新标记物进行排名。因此，重要的是要考虑标记物相关结构以进行此类研究。由于其复杂性，可能需要一种仿真方法来充分评估样本大小或其他方面，例如性能指标的选择。
方法：在基于真实数据的模拟研究中，我们调查了如何生成具有实际分布的协变量，以及应使用哪种生成模型进行结果计算，旨在确定获得实际结果所需的最少信息量和复杂度。大型流行病学队列研究作为模拟的基础，使用了古腾堡健康研究。对标记的增加值进行量化，并在该总体数据的子采样数据集中进行排名，并根据排名的质量来判断模拟方法。评估方法之一是随机森林，它需要各个级别的原始数据。因此，还研究了基于随机森林的模拟试验研究规模的影响。
结果：我们发现简单的逻辑回归模型无法充分生成现实数据，即使具有交互项或非线性效应等扩展。人们认为，随机森林方法更适合于复杂数据结构的仿真。从大约250个观察值开始的试点研究被认为为该方法提供了合理水平的信息。
结论：我们建议避免过度简化的回归模型进行仿真，尤其是在关注多变量研究问题时。更一般而言，模拟应基于真实数据，以充分反映复杂的观察数据结构，例如流行病学队列研究中发现的结构。

BACKGROUND & AIMS: Context:Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective:To perform a meta-analysis of studies evaluating the impact of Vitamin D deficiency on common carotid artery IMT (CCA-IMT) and on the prevalence of carotid plaques. Data Sources:Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results:Twenty-one studies (3,777 Vitamin D deficiency patients and 4,792 controls) with data on CCA-IMT and 6 studies (1,889 Vitamin D deficiency patients and 2,883 controls) on the prevalence of carotid plaques were included. Compared to controls, Vitamin D deficiency patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.043 mm; 95%CI: 0.030, 0.056; P<0.001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.29, 95%CI: 1.03-5.11; P=0.043) with an attributable risk of 35.9%. When selecting studies specifically including patients with diabetes, the prevalence of carotid plaques in Vitamin D deficiency patients than in controls resulted higher (OR: 3.27; 95%CI: 1,62-6.62; P=0.001). A significant difference in CCA-IMT was confirmed when comparing patients with Vitamin D insufficiency to controls (MD: 0.011; 95%CI: 0.010-0.012, P<0.001). Sensitivity analyses substantially confirmed results and regression models showed that with the exception of LDL-cholesterol, HDL-cholesterol, triglycerides and the prevalence of hypercholesterolemia, all the other clinical and demographic co-variates significantly impacted on the difference in CCA-IMT between Vitamin D deficiency patients and controls. Conclusions:Both Vitamin D deficiency and Vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.

背景与目标： 背景：维生素D缺乏症患者的心血管（CV）发病率和死亡率增加。颈动脉内膜中层厚度（IMT）和颈动脉斑块是亚临床动脉粥样硬化的标志物和CV事件的预测因子。
目的：进行荟萃分析，评估维生素D缺乏对颈总动脉IMT（CCA-IMT）和颈动脉斑块患病率的影响。
数据来源：在PubMed，Web of Science，Scopus和EMBASE数据库中系统地搜索了研究。
结果：包括21项研究（3,777例维生素D缺乏症患者和4,792例对照者）的CCA-IMT数据和6项研究（1,889例D维生素D缺乏症患者和2,883例对照者）的颈动脉斑块患病率。与对照组相比，维生素D缺乏症患者的CCA-IMT显着更高（平均差异[MD]：0.043毫米； 95％CI：0.030，0.056； P <0.001），并且颈动脉斑块的患病率增加（几率[OR] ]：2.29，95％CI：1.03-5.11； P = 0.043），归因风险为35.9％。在选择专门针对糖尿病患者的研究时，维生素D缺乏症患者的颈动脉斑块患病率高于对照组（OR：3.27； 95％CI：1,62-6.62； P = 0.001）。当将维生素D功能不足的患者与对照组进行比较时，证实了CCA-IMT的显着差异（MD：0.011； 95％CI：0.010-0.012，P <0.001）。敏感性分析基本证实了结果，回归模型显示，除了低密度脂蛋白胆固醇，高密度脂蛋白胆固醇，甘油三酸酯和高胆固醇血症的患病率外，所有其他临床和人口统计学共同变量均显着影响维生素D之间CCA-IMT的差异缺乏患者和对照。
结论：维生素D缺乏症和维生素D缺乏症均与亚临床动脉粥样硬化有关，可能提示在这些临床情况下CV风险增加。