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: BACKGROUND:Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE:To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN:Prospective, double-blind, placebo-controlled trial. SETTING:Tertiary referral university hospital. PATIENTS:A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS:Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS:Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS:There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS:Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.

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: BACKGROUND:The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC. PATIENTS AND METHODS:One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events). RESULTS:The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%). CONCLUSIONS:Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number ACTRN12610000845033, www.anzctr.org.au.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). METHODS:In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n=38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. RESULTS:Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. CONCLUSIONS:White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.

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: 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: :The present study utilized longitudinal data from a high-risk community sample (N = 377; 166 trauma-exposed; 202 males; 175 females; 73% non-Hispanic Caucasian) to test pretrauma measures of adolescent internalizing and externalizing symptoms as unique prospective predictors of type of trauma exposure and PTSD over and above the influence of correlated family adversity (a composite of family conflict, stress, and parental psychopathology). Data were analyzed with logistic and multinomial logistic regressions. Results indicated that females, but not males, with higher levels of internalizing (OR = 2.91) and externalizing (OR = 2.37) symptoms during adolescence were significantly more likely to be exposed to assaultive violence (over and above family adversity). In fact, males with higher levels of internalizing symptoms were significantly less likely to be exposed to assaultive violence (OR = 0.54). Neither internalizing nor externalizing symptoms uniquely predicted exposure to traumatic events that did not involve assaultive violence. Among trauma-exposed participants, the unique association between internalizing symptoms and later PTSD yielded an odds ratio of 1.79 (p = .07) over and above the influences of family adversity, type of trauma exposure, and gender. Assaultive violence exposure fully mediated the association between females' externalizing symptoms and future PTSD. Findings may help inform the prevention of both assaultive violence exposure and PTSD.

背景与目标： : 本研究利用了来自高风险社区样本的纵向数据 (N = 377; 166创伤暴露; 202男性; 175女性; 73% 非西班牙裔高加索人) 测试青少年内在化和外在化症状的创伤前措施，作为创伤暴露类型和创伤后应激障碍的独特前瞻性预测因子，超越相关家庭逆境 (家庭冲突、压力和父母心理病理学的组合) 的影响。数据采用logistic和多项logistic回归分析。结果表明，女性而不是男性，在青春期具有较高水平的内在化 (或 = 2.91) 和外在化 (或 = 2.37) 症状的女性更容易遭受攻击性暴力 (超过家庭逆境)。事实上，具有较高水平内化症状的男性暴露于攻击性暴力的可能性显著降低 (OR = 0.54)。内部化或外部化症状都不能唯一地预测暴露于不涉及攻击性暴力的创伤事件。在创伤暴露的参与者中，内在化症状与后来的PTSD之间的独特关联产生了1.79的优势比 (p = .07)，超出了家庭逆境，创伤暴露类型和性别的影响。攻击性暴力暴露充分介导了女性外在症状与未来创伤后应激障碍之间的关联。研究结果可能有助于预防攻击性暴力暴露和PTSD。

BACKGROUND & AIMS: :Two-hundred and ninety-three patients without a previous vaginal delivery were randomized to intracervical/extra-amniotic application of 0.5 mg prostaglandin E2 (PGE2) or to gel only. Of the patients who received PGE2, 18.7% were admitted before the next morning due to spontaneous abortion, bleeding or pains. No other side-effect was observed. A statistically significant dilatation of the cervical canal was found in the prostaglandin group. Thirty percent of the treated patients did not need further dilatation of the cervix 25.4% were non-responders to PGE2 and 7.7% were hyper-responders. The number of uterine perforations, pelvic inflammatory disease (PID) or retained pregnancy products were not influenced by the pretreatment with PGE2.

背景与目标： : 两百九十三名先前没有阴道分娩的患者被随机分配到宫颈内/羊膜外应用0.5 mg前列腺素E2 (PGE2) 或仅凝胶。在接受PGE2的患者中，有18.7% 人因自然流产，出血或疼痛而在第二天早晨之前入院。未观察到其他副作用。在前列腺素组中发现了具有统计学意义的宫颈管扩张。30% 的接受治疗的患者不需要进一步扩张子宫颈，25.4% 是对PGE2无反应的患者，7.7% 是高反应的患者。Pge2预处理不会影响子宫穿孔，盆腔炎 (PID) 或保留的妊娠产物的数量。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVE:Shared decision making and advance planning in end-of-life decisions have become increasingly important aspects of the management of seriously ill patients. Here, we describe the use and timing of do-not-resuscitate (DNR) orders in patients hospitalized with acute myocardial infarction (AMI). STUDY DESIGN AND SETTING:The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007. RESULTS:One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among patients with DNR orders, there was a significant increase in orders written prior to hospitalization (2001: 9%; 2007: 55%). Older patients and those with a medical history of heart failure or myocardial infarction were more likely to have prior DNR orders than respective comparison groups. Patients with prior DNR orders were less likely to die 1 month after hospitalization than patients whose DNRs were written during hospitalization. CONCLUSION:Although the use of DNR orders in patients hospitalized with AMI was stable during the period under study, in more recent years, patients are increasingly being hospitalized with DNR orders already in place.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. OBJECTIVE:the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. METHODS:this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. RESULTS:at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. CONCLUSION:the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.

背景与目标：

BACKGROUND & AIMS: PURPOSE:To investigate the epidemiology and clinicopathological management for ocular sebaceous carcinoma (OSC) in the UK. METHODS:Observational prospective cohort study of patients with newly-diagnosed OSC. The British Ophthalmological Surveillance Unit captured incident cases of OSC between 2008 and 2010. Incident and 6-month follow-up questionnaires from reporting ophthalmologists captured OSC demographic and clinical data. RESULTS:Data were available on 51 patients with unilateral OSC (response rate 85%). The UK estimated annual incidence was 0.41 cases per million population (95% CI 0.31 to 0.54). Median age was 70 years (SD 14, range 28-98) with 57% women. OSC location was upper lid (54%), lower lid (20%), multicentric (14%) and caruncle (12%). Most common misdiagnoses included chalazion (42%), basal cell carcinoma (30%) and blepharoconjunctivitis (16%), with median delay in diagnosis of 10 months (SD 9, range 0.5-36). Specialist ophthalmic pathologists performed diagnostics in 62%, with pagetoid/intraepithelial spread present in 39%. Misdiagnosis of chalazion (p=0.019) and pagetoid tumour spread (p=0.016) was associated with a significant diagnostic delay (one-way ANOVA/R(2)). Primary surgical management involved excision with reconstruction (49%), primary exenteration (10%) and Mohs surgery (8%). There were three deaths (out of 51) during the study period; one patient died of OSC-related disease and the other two due to other causes. CONCLUSIONS:This population-based prospective study confirms OSC as a rare cancer in the UK. Masquerade syndromes result in significant diagnostic delays and increase the risk of pagetoid tumour spread. There is considerable UK variation in pathological and surgical management, and ocular reconstruction and radical surgery is often required for OSC due to delayed presentation.

背景与目标：