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： : 分布式基因组假说 (DGH) 指出，细菌物种中的每个菌株都从基于群体的上基因组接收到独特的基因分布，该基因分布比任何给定菌株的基因组大很多倍。观察到自然感染种群通常是多克隆的，并且大多数慢性细菌病原体具有高度发达的水平基因转移机制，这表明DGH并提供了手段和机制来解释慢性感染如何在哺乳动物宿主的适应性防御机制中持续存在。先前已经确定了DGH对专性病原体的有效性，我们希望评估其对机会性细菌病原体的适用性。这是通过构建和分析包含约216,000个功能克隆的高度冗余的合并基因组文库来实现的，所述基因组文库是从铜绿假单胞菌的12个低传代临床分离株、6个耳鼻喉科分离株和6个来自其他身体位点构建的。对从该文库中随机挑选的3,214个克隆 (平均插入大小，约1.4 kb) 的序列分析表明，对于铜绿假单胞菌原型菌株pao1的所有基因组序列，348 (10.8%) 的克隆是独特的。这些独特序列中开放阅读框的假设翻译证明了蛋白质与许多细菌毒力因子和其他以前在铜绿假单胞菌中未鉴定的蛋白质的同源性。进行了PCR和基于逆转录PCR的检测，以分析11种临床菌株中这些序列的70个开放阅读框子集的分布和表达模式。这些序列在临床分离株中分布不均匀，近一半 (34/70) 新序列仅存在于单个菌株中的一个或两个中。表达谱分析显示，这些序列中的绝大多数都被表达，这强烈表明它们编码功能蛋白。

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：

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：

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： 先前对细菌视紫红质的诱变研究表明，席夫碱的再质子化是D96N突变体光循环中的限速步骤，而视网膜再异构化和蛋白质返回到初始状态则构成了光循环中的限速事件。L93A突变体。因此，在D96N突变体中，M中间体的衰变在ph7下减慢了100倍以上。在L93A突变体中，O中间体的衰变减慢250倍。我们在这里报告说，在L93A，D96N双突变体中，M中间体的衰变以及O中间体的形成和衰变显着减慢。像L93A突变体一样，通过长寿命O中间体的衰变来完成光循环。双突变体中M和O中间体的衰变与在宽温度和pH范围内单个突变体中看到的行为相似，认为观察到的独立性是突变体的内在特性。M和O中间体的缓慢衰变可以在与D96N和L93A单个突变体中相应中间体所使用的条件相同的条件下选择性地和独立地逆转。由于两个个体突变的作用保留在双突变体中并且可以独立逆转，因此我们得出结论，残基Asp 96和Leu 93独立且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，并且与水性介质中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：

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： : 在急诊科对新发癫痫患者的评估中，经常进行广泛的实验室测试。为了确定这种测试的实用性，对向市中心大学附属教学医院的ED呈递的新发癫痫发作患者进行了前瞻性研究。在1984年10月和1988年1月之间，有136名患者进入了研究。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促成原因之前，将相关的历史信息和体格检查结果记录在标准化表格上。其中包括4名低血糖患者，4名高血糖患者，2名低钙血症患者和1名低镁血症患者。根据病史或体格检查发现，仅怀疑有2例 (低血糖)。在ED患者中，由于可纠正的代谢紊乱而引起的新发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，通常不需要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的检查顺序应由病史和体格检查指示。

BACKGROUND & AIMS: :The effect of different seasons on sterol content of seafoods was investigated. There were four sterols (cholesterol, sitosterol, desmosterol and stigmasterol) identified, with cholesterol being the predominant sterol. Stigmasterol was a minor component in fish muscle, whilst sitosterol was one of the main phytosterols found in fish muscle. Cholesterol content of fish consisted of 38-100% of total sterols in fish and 54-80% of total sterols in shellfish. The highest cholesterol content of fish muscle was found in summer and the lowest in autumn, whereas season did not have any effect on cholesterol level of green tiger prawn and speckled shrimp. Total sterol content of fish muscle ranged from 49 to 110 mg/100 g, although the range of total sterols in shrimp muscle was between 62 and 91 mg/100 g. The result of the study showed that total sterols in fish were generally found at lower levels in winter compared with other seasons.

背景与目标： : 研究了不同季节对海鲜中固醇含量的影响。鉴定出四种固醇 (胆固醇，谷甾醇，去甾醇和豆甾醇)，其中胆固醇是主要的固醇。豆甾醇是鱼类肌肉中的次要成分，而谷甾醇是鱼类肌肉中发现的主要植物甾醇之一。鱼的胆固醇含量由鱼中38-100% 的总甾醇和贝类中54-80% 的总甾醇组成。夏季发现鱼肌肉中胆固醇含量最高，秋季最低，而季节对绿虎虾和斑点虾的胆固醇水平没有任何影响。鱼肌肉的总固醇含量范围为49至110 mg/100g，尽管虾肌肉中的总固醇含量范围为62至91 mg/100g。研究结果表明，与其他季节相比，冬季鱼中的总固醇含量通常较低。

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：

BACKGROUND & AIMS: :Strongylocentrotus nudus is an edible sea urchin, mainly harvested in China. Correlation studies indicated that S. nudus with larger diameter have a prolonged marketing time and better palatability owing to their precocious gonads and extended maturation process. However, the molecular mechanism underlying this phenomenon is still unknown. Here, transcriptome sequencing was applied to study the ovaries of adult S. nudus with different shell diameters to explore the possible mechanism. In this study, four independent cDNA libraries were constructed, including two from the big size urchins and two from the small ones using a HiSeq™2500 platform. A total of 88,581 unigenes were acquired with a mean length of 1354bp, of which 66,331 (74.88%) unigenes could be annotated using six major publicly available databases. Comparative analysis revealed that 353 unigenes were differentially expressed (with log2(ratio)≥1, FDR≤0.001) between the two groups. Of these, 20 differentially expressed genes (DEGs) were selected to confirm the accuracy of RNA-seq data by quantitative real-time RT-PCR. Furthermore, gene ontology and KEGG pathway enrichment analyses were performed to find the putative genes and pathways related to ovarian maturity. Eight unigenes were identified as significant DEGs involved in reproduction related pathways; these included Mos, Cdc20, Rec8, YP30, cytochrome P450 2U1, ovoperoxidase, proteoliaisin, and rendezvin. Our research fills the gap in the studies on the S. nudus ovaries using transcriptome analysis.

背景与目标： : Strongylocentrotus nudus是一种可食用的海胆，主要在中国收获。相关研究表明，直径较大的S. nudus由于其早熟的性腺和成熟过程的延长，具有延长的销售时间和更好的适口性。然而，这种现象背后的分子机制仍然未知。在此，将转录组测序用于研究具有不同壳直径的成年S. nudus的卵巢，以探讨其可能的机制。在这项研究中，使用HiSeq构建了四个独立的cDNA文库，其中两个来自大海胆，两个来自小海胆。™2500平台。总共获得了88,581个单基因，平均长度为1354bp，其中66,331个 (74.88% 个) 单基因可以使用六个主要的公开数据库进行注释。比较分析显示，两组之间353单基因差异表达 (log2 (比率) ≥ 1，fdr ≤ 0.001)。其中，选择了20个差异表达基因 (deg)，以通过定量实时rt-pcr确认RNA-seq数据的准确性。此外，还进行了基因本体论和KEGG途径富集分析，以找到与卵巢成熟度相关的推定基因和途径。八个单基因被鉴定为参与生殖相关途径的重要deg; 这些包括Mos，Cdc20，Rec8，YP30，细胞色素P450 2U1，卵巢过氧化物酶，蛋白毒素和rendezvin。我们的研究填补了使用转录组分析对卵巢S. nudus卵巢的研究的空白。

BACKGROUND & AIMS: :The accuracy of two new 4-h identification systems for anaerobes, the AN-IDENT (Analytab Products, Plainview, N.Y.) and the RapID ANA (Innovative Diagnostic Systems, Inc., Atlanta, Ga.) was compared with that of the API 20A system (Analytab Products). A total of 132 clinical isolates were tested in each of the three systems. The overall accuracies at the genus and species level for the three systems were: API 20A, 68.9 and 56.8%, respectively; AN-IDENT, 90.2 and 73.5%; and RapID ANA, 93.9 and 81.8%. Improved identification of anaerobes with the AN-IDENT and the RapID ANA systems was observed for isolates of the genus Fusobacterium, Clostridium species other than Clostridium perfringens, non-spore-forming bacilli, and isolates of the genus Peptostreptococcus. Reproducibility studies demonstrated that the results of the individual test reactions in all three identification systems were reproducible when the interpretive guidelines of the manufacturer were followed precisely.

背景与目标： : 将两种新的4小时厌氧菌识别系统的准确性，即AN-IDENT (Analytab Products，纽约州Plainview) 和RapID ANA (Innovative Diagnostic systems，inc.，乔治亚州亚特兰大) 与API 20A系统 (Analytab产品)。在这三个系统中的每个系统中总共测试了132个临床分离株。这三个系统在属和种级别的总体精度分别为: API 20A，68.9和56.8%; A-IDENT，90.2和73.5%; 和快速ANA，93.9和81.8%。对于梭菌属，除产气荚膜梭状芽孢杆菌以外的梭状芽孢杆菌属，非孢子形成杆菌和消化链球菌属的分离株，观察到an-ident和快速ANA系统对厌氧菌的鉴定得到了改善。可重复性研究表明，当精确遵循制造商的解释准则时，所有三个识别系统中单个测试反应的结果都是可重现的。

BACKGROUND & AIMS: :A consensus regarding the therapeutic role of lymphadenectomy in endometrial cancer has not been reached because of conflicting negative results of randomized controlled trials and positive results of a cohort study. Since the effects of new treatments tend to be overestimated in observational studies, positive results of an observational study should be validated by a future trial. However, special difficulties are presented in randomized controlled trials in surgery. External validity is important for guaranteeing the reliability of a result of the trial. Physicians' recruitment of eligible patients into a trial depends on the confidence of those physicians for a surgical procedure, workplace environment and feelings of personal responsibility relevant to patients' risk of recurrence. When two surgical procedures are compared in a randomized controlled trial, technical quality control may be reduced in the complicated surgery group due to experienced surgeons' non-participation. It is highly possible that the recruitment issue is a threat to external validity. Therefore, a randomized controlled trial may not be the best format for demonstrating the full benefits of complicated surgery. Multiple studies have demonstrated that the results of well-designed observational studies can be reliable and are comparable with those of randomized controlled trials. Journal editors and funding sources are requested to become more generous with observational studies, especially prospective cohort studies.

背景与目标： : 由于随机对照试验的阴性结果与队列研究的阳性结果相互矛盾，因此尚未就淋巴结清扫术在子宫内膜癌中的治疗作用达成共识。由于在观察性研究中往往高估了新疗法的效果，因此观察性研究的阳性结果应通过未来的试验来验证。然而，在外科手术的随机对照试验中存在特殊困难。外部有效性对于保证试验结果的可靠性很重要。医生是否招募合格的患者参加试验取决于这些医生对外科手术，工作场所环境以及与患者复发风险相关的个人责任感的信心。在随机对照试验中比较两种手术方法时，由于经验丰富的外科医生不参与，复杂手术组的技术质量控制可能会降低。招聘问题很有可能威胁到外部有效性。因此，随机对照试验可能不是证明复杂手术的全部益处的最佳形式。多项研究表明，精心设计的观察性研究的结果是可靠的，并且与随机对照试验的结果相当。要求期刊编辑和资金来源对观察性研究，尤其是前瞻性队列研究更加慷慨。

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。在没有促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T细胞作用。在18例血清中甲状腺球蛋白抗体滴度较高的患者中，有8例 (44% 例) 发现了Tg PFC。在t-b MC系统中，使用这八名患者的b细胞研究了患者和正常受试者的T细胞对Tg的特异性和非特异性免疫调节。添加T细胞后，与Prot A PFC诱导相比，Tg PFC诱导值明显降低。正常T细胞抑制Tg PFC诱导，但患者T细胞不抑制，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。来自患者和正常受试者的T细胞的照射 (1500 rads) 显着增强了TgPFC和Prot A PFC的诱导。因此，Tg特异性抑制T细胞作为放射敏感性抑制T细胞亚群的一部分存在于所有正常受试者中。在正常受试者中，由辐射诱导的Tg特异性抑制T细胞功能抑制引起的tg-pfc的增加明显大于患者。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，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，可以使用来自血清中Tg抗体滴度较高的自身免疫性甲状腺疾病患者的b细胞，在t-b MC系统中研究体外Tg特异性T细胞调控。Tg特异性抑制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，不是完整的，而是Tg特异性抑制T细胞的相对缺陷。

BACKGROUND & AIMS: :Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 log10 units within 2-4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (greater than or equal to 99.9% reduction of viable counts at 4-22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringens.

背景与目标： : 检查了24种抗菌药物对选定的产气荚膜梭菌菌株的起效速度和杀菌活性。头孢曲松，亚胺培南，甲硝唑，美洛西林，青霉素g，哌拉西林和替考拉宁在暴露后2-4小时内将菌落计数减少至少3 log10单位。克林霉素，氟喹诺酮类，交沙霉素和四环素引起延迟杀伤 (暴露后4-22小时活菌计数大于或等于99.9% 减少)。氯霉素和利福平对4株菌株中的2株缺乏杀菌活性，而红霉素，夫西地酸和磷霉素 (添加了6-磷酸葡萄糖) 仅对所有4株菌株具有抑制作用。亚胺培南和青霉素g分别与9种和12种抗菌药物联合使用。基本上所有的药物组合都产生不同的效果; 只有青霉素g加强力霉素导致对产气荚膜炎的拮抗作用。

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：

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.

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