bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial-Resistant Strains of Clostridium difficile from North America
Authors: Tenover Fred C. , Tickler Isabella A. , Persing David H. 
Published: March 2012

ABSTRACT

A total of 316 toxigenic
Clostridium difficile
clinical isolates of known PCR ribotypes from patients in North America were screened for resistance to clindamycin, metronidazole, moxifloxacin, and rifampin. Clindamycin resistance was observed among 16 different ribotypes, with ribotypes 017, 053, and 078 showing the highest proportions of resistance. All isolates were susceptible to metronidazole. Moxifloxacin resistance was present in >90% of PCR-ribotype 027 and 053 isolates but was less common among other ribotypes. Only 7.9% of the
C. difficile
isolates were resistant to rifampin. Multidrug resistance (clindamycin, moxifloxacin, and rifampin) was present in 27.5% of PCR-ribotype 027 strains but was rare in other ribotypes. These results suggest that antimicrobial resistance in North American isolates of
C. difficile
varies by strain type and parallels rates of resistance reported from Europe and the Far East.
Reduced Antituberculosis Drug Concentrations in HIV-Infected Patients Who Are Men or Have Low Weight: Implications for International Dosing Guidelines
Authors: McIlleron Helen , Rustomjee Roxana , Vahedi Mahnaz , Mthiyane Thuli , Denti Paolo , Connolly Catherine , Rida Wasima , Pym Alexander , Smith Peter J. , Onyebujoh Philip C. 
Published: March 2012

ABSTRACTReduced antituberculosis drug concentrations may contribute to unfavorable treatment outcomes among HIV-infected patients with more advanced immune suppression, and few studies have evaluated pharmacokinetics of the first-line antituberculosis drugs in such patients given fixed-dose combination tablets according to international guidelines using weight bands. In this study, pharmacokinetics were evaluated in 60 patients on 4 occasions during the first month of antituberculosis therapy. Multilevel linear mixed-effects regression analysis was used to examine the effects of age, sex, weight, drug dose/kilogram, CD4+lymphocyte count, treatment schedule (5 versus 7 days/week), and concurrent antiretrovirals (efavirenz plus lamivudine plus zidovudine) on the area under the concentration-time curve from 0 to 12 h (AUC0-12) of the respective antituberculosis drugs and to compare AUC0-12s at day 8, day 15, and day 29 with the day 1 AUC0-12. Median (range) age, weight, and CD4+lymphocyte count were 32 (18 to 47) years, 55.2 (34.4 to 98.7) kg, and 252 (12 to 500)/μl. For every 10-kg increase in body weight, the predicted day 29 AUC0-12increased by 14.1% (95% confidence interval [CI], 7.5, 20.8), 14.1% (95% CI, −0.7, 31.1), 6.1% (95% CI, 2.7, 9.6) and 6.0% (95% CI, 0.8, 11.3) for rifampin, isoniazid, pyrazinamide, and ethambutol, respectively. Males had day 29 AUC0-12s 19.3% (95% CI, 3.6, 35.1) and 14.0% (95% CI, 5.6, 22.4) lower than females for rifampin and pyrazinamide, respectively. Level of immune suppression and concomitant antiretrovirals had little effect on the concentrations of the antituberculosis agents. As they had reduced drug concentrations, it is important to review treatment responses in patients in the lower weight bands and males to inform future treatment guidelines, and revision of doses in these patients should be considered.
Comparison of resident and mid-level provider productivity and patient satisfaction in an emergency department fast track
Authors: Jeanmonod Rebecca , DelCollo Jessica , Jeanmonod Donald , Dombchewsky Orest , Reiter Mark 
Published: March 2012

ObjectiveTo evaluate productivity of mid-level providers (MLPs) compared with emergency medicine (EM) resident physicians in an emergency department (ED) low acuity area, and to compare patient satisfaction when cared for by MLPs versus EM residents.MethodsThis was a retrospective review of EM resident physicians and MLPs in an ED low acuity area. The number of patients seen and relative value units (RVUs) generated per clinical hour worked were evaluated. A t test was used to compare resident and MLP productivity. Additionally, patients were prospectively surveyed to assess satisfaction, using survey items based on the Press-Ganey survey. Non-parametric statistics were used to analyse patient satisfaction scores.ResultsMLPs treated 2.21 patients per hour (CI ±0.09), while resident physicians treated 1.53 patients per hour (CI ±0.08). MLPs generated 4.01 RVUs per hour (CI ±0.18) while resident physicians generated 3.14 RVUs per hour (CI ±0.18). Resident physicians generated 2.07 RVUs per patient (CI ±0.08) while MLPs generated 1.82 RVUs per patient (CI ±0.03; p<0.001). Of the 201 completed satisfaction surveys, 126 patients were seen by MLPs and 75 were seen by residents. Overall patients were highly satisfied with their ED visit. There were no differences in any survey responses based on provider type or resident level of training.ConclusionIn a low acuity area of the ED, MLPs treated more patients per hour and generated more RVUs per hour than EM resident physicians. However, resident physicians generated more RVUs per patient. Patient satisfaction did not differ.
Clinicopathological significance of podocalyxin and phosphorylated ezrin in uterine endometrioid adenocarcinoma
Authors: Yasuoka Hironao , Tsujimoto Masahiko , Inagaki Michiya , Kodama Rieko , Tsuji Hiromi , Iwahashi Yoshifumi , Mabuchi Yasushi , Ino Kazuhiko , Sanke Tokio , Nakamura Yasushi 
Published: March 2012

BackgroundPodocalyxin is an anti-adhesive glycoprotein that has been associated with highly aggressive forms of cancers. Podocalyxin increases the migration and invasive properties of cancer cells through its interaction with ezrin, which undergoes an increase in phosphorylation through podocalyxin.AimsTo study the roles of podocalyxin and phosphorylated ezrin (pEzrin) in uterine endometrioid adenocarcinoma (UEA).MethodsUsing immunohistochemisty the authors investigated the expression of podocalyxin and pEzrin along with some well-known markers of tumour aggressiveness including p53, oestrogen receptor and Ki-67 in UEA.ResultsPodocalyxin and pEzrin expression levels were positive in 36.1% (22 of 61 patients) and 50.8% (31 of 61 patients) of UEA cases, respectively. Further, podocalyxin expression was correlated with tumour grade (p=0.0001), FIGO stage (p=0.0062), p53 expression (p=0.0050) and Ki-67 index (p=0.0069). In addition, pEzrin expression was associated with FIGO stage (p=0.0231), p53 expression (p<0.0001) and Ki-67 index (p=0.0010). The expression of podocalyxin was also correlated with that of pEzrin (p=0.0102).ConclusionsThese results suggest that overexpression of podocalyxin and pEzrin may indicate a more aggressive phenotype; thus, evaluation of these proteins may be useful in prediction of disease progression in UEA cases.
Determination of serum aldosterone by liquid chromatography and tandem mass spectrometry: a liquid–liquid extraction method for the ABSCIEX API-5000 mass spectrometry system
Authors: Van Der Gugten Jessica Grace , Dubland Joshua , Liu Hua-Fen , Wang Alex , Joseph Christine , Holmes Daniel T 
Published: March 2012

AimsAccurate serum aldosterone determination is critical to the screening and diagnosis of primary aldosteronism, the localisation of aldosterone producing tumours, and the investigation of other disorders of the renin-angiotensin system. Mass spectrometry offers a means to overcome problems with method-dependent bias between competitive immunoassays for aldosterone. The authors have developed a simple, sensitive and precise liquid–liquid extraction aldosterone method for the ABSCIEX API-5000 liquid chromatography and tandem mass spectrometry (LC-MS/MS) system.MethodsUsing d7-aldosterone internal standard, 500 μl of sample is extracted with 2500 μl of methyl tertbutyl ether followed by dry-down, reconstitution and LC-MS/MS analysis in ESI negative mode. Method validation was undertaken using standard approaches and comparison made against a commercial radioimmunoassay. Accuracy was assessed using EQA material with assigned aldosterone concentrations.ResultsThe assay was linear up to 3420 pmol/l (LOQ=50 pmol/l, LOD<22 pmol/l). Total CVs were ≤5% for concentrations ≥120 pmol/l and 10% at the LOQ. Mean accuracy was 98.5% against GCMS assigned material.ConclusionThe authors present a precise, sensitive and simple aldosterone method suitable for routine clinical use that requires no solid phase extraction or specialised ion sources.
Troponin testing in the emergency department: a longitudinal study to assess the impact and sustainability of decision support strategies
Authors: Georgiou Andrew , Lam Mary , Allardice Jane , Hart Graeme K , Westbrook Johanna I 
Published: March 2012

AimTo evaluate the impact of decision support on the proportion of troponin I (cTnI) tests and associated costs over the period 2000–7 for patients presenting with chest pain in an emergency department (ED) setting.MethodsA longitudinal study using linked data for patients presenting with chest pain from the ED and laboratory information systems of a metropolitan teaching hospital in Melbourne, Australia. The study period was divided into a pre-intervention period (2000–2), which contained no decision support; an initial post period (2003–4) after the introduction of a quality improvement initiative (utilising a paper-based guideline, education, audit and feedback) about cTnI test ordering and the incorporation of the guideline as a decision support feature of the computerised provider order entry system; followed by a post-modification period (2005–7) after the electronic decision support feature was modified to allow clinicians to bypass viewing the complete guideline.ResultsThere was a significant fall in the proportion of cTnI tests ordered per patient presentation across the three periods—pre (2000–2), post (2003–4) and post-modification (2005–7)—from 7.3% to 4.1% and 2.8%, respectively. Analysis of costs showed significant reductions in the mean costs for cTnI tests per patient presentation from $A9.28 to $A8.54 and $A8.18, respectively, which amounted to a modest saving of $A13 251 since the initiation of decision support in 2003.ConclusionsDecision support systems are often part of multifaceted implementations undertaken over time. They require continuous monitoring and modifications to ensure optimal performance.
Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma
Authors: Enomoto Yasunori , Kasai Takahiko , Takeda Maiko , Takano Masato , Morita Kohei , Kadota Eiji , Iizuka Norishige , Maruyama Hiroshi , Haratake Joji , Kojima Yu , Ikeda Naoya , Inatsugi Naoki , Nonomura Akitaka 
Published: March 2012

BackgroundEpidermal growth factor receptor (EGFR) gene mutation at the kinase domain and EGFR gene amplification are reported to be predictors of the response to EGFR tyrosine kinase inhibitors in lung cancer cases. In malignant mesothelioma (MM), the role of EGFR is less clear.MethodsThirty-eight MM specimens were submitted to EGFR mutation evaluation, and compared with the results of immunohistochemical staining and fluorescencein situhybridization (FISH) analysis. DNA was extracted from paraffin blocks and PCR was performed to amplify exon regions 18–21 of the EGFR gene. Direct sequencing of the purified PCR products was performed.ResultsFive EGFR missense mutations were detected in six of the 38 patients (16%); two of these mutations were novel, two were originally detected in non-small cell lung carcinoma, and one resembled a location previously noted for malignant peritoneal mesothelioma.ConclusionAs far as the authors are aware there has been no report of the EGFR mutation of MM in Japanese cases, but in this study EGFR missense mutations were detected in some cases. EGFR mutation results were not related to immunohistochemical and FISH analysis.
Association of risky alcohol consumption and accreditation in the ‘Good Sports’ alcohol management programme
Authors: Rowland Bosco , Allen Felicity , Toumbourou John W 
Published: March 2012

BackgroundInvolvement in community sports clubs is often associated with high levels of risky alcohol consumption; however, developing prevention-focused interventions in these settings can be complex. We examined the association of reduced risky alcohol consumption with the implementation of the Good Sports Programme (GSP)—a programme that accredits clubs in three stages, on the basis of their implementation of alcohol-related harm reduction strategies.MethodsUsing a cross section of football and cricket clubs, consumption was compared between clubs accredited at level 1, 2 or 3 of the GSP and clubs not accredited (92 clubs; 1924 individuals). Drinking above Australian guidelines for short-term risk (more than four standard drinks) on the last playing day prior to the survey and drinking at the club over the last 12 months at average levels exceeding short- and long-term risk (more than two standard drinks) guidelines were also examined.ResultsMultilevel modelling indicated that higher accreditation stage (0, 1, 2, 3) was associated with a 0.79 reduction in the odds of risky consumption on the playing day; a 0.85 reduction in the odds for short-term risky drinking, and a 0.86 reduction in long-term risky drinking.ConclusionsThe findings suggest that higher accreditation in the GSP is associated with reduced rates of risky alcohol use at a population level.
The design and development of the server efficiency rating tool (SERT) (abstracts only)
Authors: Lange Klaus-Dieter , Tricker Michael G. 
Published: March 2012

According to the United States Environmental Protection Agency (US EPA) almost 3% of all electricity consumed within the US in 2010 goes to running datacenters, with the majority of that powering servers and the associated air conditioning systems dedicated to eliminating the heat they produce. The EPA launched the ENERGY STARR Computer Server program in May 2009, intended to deliver information to better enable server purchasing decisions based on projected power consumption.
The Server Efficiency Rating Tool (SERT)" has been developed by the Standard Performance Evaluation Corporation (SPEC) SPECpower committee to address the EPA requirements for Version 2 of the ENERGY STAR server program. Unlike many tools sourced from the SPEC organization the SERT is not intended to be a benchmark, and for Version 2 does not offer a single score model. Instead it produces detailed information regarding the influence of CPU, memory, network and storage I/O configurations on overall server power consumption.
This paper describes the design and development of the SERT, including discussion of the collaborative nature of working with the EPA and the various industry stakeholders involved in the design, review and development process. Many of the core ideas behind SERT were derived from the SPECpower ssj2008 and other SPEC-developed benchmarks, and this paper illustrates where ideas and code were shared, as well as where new thinking resulted in entirely new solutions. It also includes thoughts for the future, as the ENERGY STAR server program continues to evolve and the SERT will evolve with it.
MT-WAVE
Authors: Arkles Anthony , Makaroff Dwight 
Published: March 2012

Modern web applications consist of many distinct services that collaborate to provide the full application functionality. To improve application performance, developers need to be able to identify the root cause of performance problems; identifying and fixing performance problems in these distributed, heterogeneous applications can be very difficult. As web applications become more complicated, the number of systems involved will continue to grow and full-system performance tuning will become more difficult.
We postulate that multi-tier profiling, starting at the web browser, is the appropriate way to solve this problem. Instrumenting from the web browser, as the user experiences it, ensures that we can tell what each service in the application is contributing to overall page-load time; thus, each tier must provide instrumentation data that developers can use to quickly identify the root cause of performance problems. We have built MT-WAVE, a system that integrates with the different tiers of a web application (including a browser extension) and collects light-weight instrumentation to a central location via X-Trace facilities. The collected data is presented with our visualization system that provides varying levels of detail.
To validate our approach, we performed case studies of two applications, both showing performance insight. In particular, we identified and fixed a significant and unintuitive bottleneck in an open-source project management application and verified caching behaviour in a cloud-hosted commercial product. While specific technologies are used in our case study, we believe that most web technologies in common use today would require straightforward modifications to be able to utilize MT-WAVE tracing facilities.
This tool is designed to be used by application developers and system administrators while testing new software, or after deployment when it becomes clear that existing performance is not meeting user needs.
A little language for rapidly constructing automated performance tests (abstracts only)
Authors: Dunning Shaun , Sawyer Darren 
Published: March 2012

In order to effectively measure the performance of large scale data management solutions at NetApp, we use a fully automated infrastructure to execute end-to-end system performance tests. Both the software and user requirements of this infrastructure are complex: the system under test runs a multi-protocol, highly specialized operating system and the infrastructure serves a diverse audience of developers, analysts, and field engineers (including both sales and support). In this paper we describe our approach to rapidly constructing automated performance system tests by using a lightweight, little, or domain-specific language called SLSL in order to more effectively express test specifications.
Using a real world example, we illustrate the efficacy of SLSL in terms of its expressiveness, flexibility, and ease of use by showing a complex test configuration expressed with just a few language constructs. We also demonstrate how SLSL can be used in conjunction with our performance measurement lab to quickly deploy performance tests that yield highly repeatable measurements..
Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100
Authors: Richards Juliet , Lim Ai Chiin , Hay Colin W. , Taylor Angela E. , Wingate Anna , Nowakowska Karolina , Pezaro Carmel , Carreira Suzanne , Goodall Jane , Arlt Wiebke , McEwan Iain J. , de Bono Johann S. , Attard Gerhardt 
Published: March 2012

Abstract
Prostate cancer progression can be associated with androgen receptor (AR) mutations acquired following treatment with castration and/or an antiandrogen. Abiraterone, a rationally designed inhibitor of CYP17A1 recently approved for the treatment of docetaxel-treated castration-resistant prostate cancer (CRPC), is often effective, but requires coadministration with glucocorticoids to curtail side effects. Here, we hypothesized that progressive disease on abiraterone may occur secondary to glucocorticoid-induced activation of mutated AR. We found that prednisolone plasma levels in patients with CRPC were sufficiently high to activate mutant AR. Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone that are used to treat side effects related to mineralocorticoid excess, can also bind to and activate signaling through wild-type or mutant AR. Abiraterone inhibited in vitro proliferation and AR-regulated gene expression of AR-positive prostate cancer cells, which could be explained by AR antagonism in addition to inhibition of steroidogenesis. In fact, activation of mutant AR by eplerenone was inhibited by MDV3100, bicalutamide, or greater concentrations of abiraterone. Therefore, an increase in abiraterone exposure could reverse resistance secondary to activation of AR by residual ligands or coadministered drugs. Together, our findings provide a strong rationale for clinical evaluation of combined CYP17A1 inhibition and AR antagonism. Cancer Res; 72(9); 2176–82. ©2012 AACR.
High TUBB3 Expression, an Independent Prognostic Marker in Patients with Early Non–Small Cell Lung Cancer Treated by Preoperative Chemotherapy, Is Regulated by K-Ras Signaling Pathway
Authors: Levallet Guénaëlle , Bergot Emmanuel , Antoine Martine , Creveuil Christian , Santos Adriana O. , Beau-Faller Michelle , de Fraipont Florence , Brambilla Elisabeth , Levallet Jérôme , Morin Franck , Westeel Virginie , Wislez Marie , Quoix Elisabeth , Debieuvre Didier , Dubois Fatéméh , Rouquette Isabelle , Pujol Jean-Louis , Moro-Sibilot Denis , Camonis Jacques , Zalcman Gérard 
Published: March 2012

Abstract
We assessed the prognostic and predictive value of β-tubulin III (TUBB3) expression, as determined by immunohistochemistry, in 412 non–small cell lung cancer (NSCLC) specimens from early-stage patients who received neoadjuvant chemotherapy (paclitaxel- or gemcitabine-based) in a phase III trial (IFCT-0002). We also correlated TUBB3 expression with K-Ras and EGF receptor (EGFR) mutations in a subset of 208 cryopreserved specimens. High TUBB3 protein expression was associated with nonsquamous cell carcinomas (P &lt; 0.001) and K-Ras mutation (P &lt; 0.001). The 127 (30.8%) TUBB3-negative patients derived more than 1 year of overall survival advantage, with more than 84 months median overall survival versus 71.7 months for TUBB3-positive patients [HR, 1.58; 95% confidence interval (CI), 1.11–2.25)]. This prognostic value was confirmed in multivariate analysis (adjusted HR for death, 1.51; 95% CI, 1.04–2.21; P = 0.031) with a bootstrapping validation procedure. TUBB3 expression was associated with nonresponse to chemotherapy (adjusted HR, 1.31; 95% CI, 1.01–1.70; P = 0.044) but had no predictive value (taxane vs. gemcitabine). Taking account of these clinical findings, we further investigated TUBB3 expression in isogenic human bronchial cell lines only differing by K-Ras gene status and assessed the effect of K-Ras short interfering RNA (siRNA) mediated depletion, cell hypoxia, or pharmacologic inhibitors of K-Ras downstream effectors, on TUBB3 protein cell content. siRNA K-Ras knockdown, inhibition of RAF/MEK (MAP–ERK kinase) and phosphoinositide 3-kinase (PI3K)/AKT signaling, and hypoxia were shown to downregulate TUBB3 expression in bronchial cells. This study is the first one to identify K-Ras mutations as determinant of TUBB3 expression, a chemoresistance marker. Our in vitro data deserve studies combining standard chemotherapy with anti-MEK or anti-PI3K drugs in patients with TUBB3-overexpressing tumors. Mol Cancer Ther; 11(5); 1203–13. ©2012 AACR.