bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing Epidemiology of Extended-Spectrum β-Lactamases in Argentina: Emergence of CTX-M-15
Authors: Sennati S. , Santella G. , Di Conza J. , Pallecchi L. , Pino M. , Ghiglione B. , Rossolini G. M. , Radice M. , Gutkind G. 
Published: August 2012

ABSTRACT

A multicenter survey, carried out in 2010 in Argentina, showed an increased prevalence of extended-spectrum β-lactamase (ESBL)-producing enterobacteria, with some changes in the molecular epidemiology of circulating ESBLs. While enzymes of the CTX-M-2 group remain endemic, the emergence of CTX-M-15 and of enzymes of the CTX-M-8 and CTX-M-9 groups was observed. The CTX-M-15-positive isolates represented 40% of CTX-M producers and included representatives of
Escherichia coli
ST131 and
Klebsiella pneumoniae
ST11.
A Randomized, Evaluator-Blind, Phase 2 Study Comparing the Safety and Efficacy of Omadacycline to Those of Linezolid for Treatment of Complicated Skin and Skin Structure Infections
Authors: Noel Gary J. , Draper Michael P. , Hait Howard , Tanaka S. Ken , Arbeit Robert D. 
Published: August 2012

ABSTRACT

A randomized, investigator-blind, multicenter phase 2 trial involving patients with complicated skin and skin structure infections (cSSSI) compared the safety and efficacy of omadacycline, a broad-spectrum agent with activity against methicillin-resistant
Staphylococcus aureus
(MRSA), to those of linezolid (with or without aztreonam). Patients were randomized 1:1 to omadacycline (100 mg intravenously [i.v.] once a day [QD] with an option to transition to 200 mg orally QD) or linezolid (600 mg i.v. twice daily [BID] with an option to transition to 600 mg orally BID) at 11 U.S. sites. Patients suspected or documented to have infections caused by Gram-negative bacteria were given aztreonam (2 g i.v. every 12 h [q12h]) if randomized to linezolid or matching placebo infusions if randomized to omadacycline. Adverse events were reported in 46 (41.4%) omadacycline-treated and 55 (50.9%) linezolid-treated patients. Adverse events related to treatment were assessed by investigators in 24 (21.6%) omadacycline-treated and 33 (30.6%) linezolid-treated patients. The gastrointestinal tract was most commonly involved, with adverse events reported in 21 (18.9%) patients exposed to omadacycline and 20 (18.5%) exposed to linezolid. Rates of successful clinical response in the intent-to-treat (ITT) and clinical evaluable (CE) populations favored omadacycline (ITT, 88.3% versus 75.9%; 95% confidence interval [CI], 1.9 to 22.9; CE, 98.0% versus 93.2%; 95% CI, −1.7 to 11.3). For microbiologically evaluable (ME) patients with
S. aureus
infections, the clinical success rates were 97.2% (70/72) in omadacycline-treated and 92.7% (51/55) in linezolid-treated patients. This phase 2 experience supports conclusions that omadacycline is well tolerated in cSSSI patients and that this aminomethylcycline has potential to be an effective treatment for serious skin infections.
Evaluation of the Novel Combination of High-Dose Daptomycin plus Trimethoprim-Sulfamethoxazole against Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Using an
In Vitro
Pharmacokinetic/Pharmacodynamic Model of Simulated Endocardial Vegetations
Authors: Steed Molly E. , Werth Brian J. , Ireland Cortney E. , Rybak Michael J. 
Published: August 2012

ABSTRACT

Daptomycin-nonsusceptible (DNS)
Staphylococcus aureus
is found in difficult-to-treat infections, and the optimal therapy is unknown. We investigated the activity of high-dose (HD) daptomycin plus trimethoprim-sulfamethoxazole de-escalated to HD daptomycin or trimethoprim-sulfamethoxazole against 4 clinical DNS methicillin-resistant
S. aureus
(MRSA) isolates in an
in vitro
pharmacokinetic/pharmacodynamic model of simulated endocardial vegetations (10
9
CFU/g). Simulated regimens included HD daptomycin at 10 mg/kg/day for 14 days, trimethoprim-sulfamethoxazole at 160/800 mg every 12 h for 14 days, HD daptomycin plus trimethoprim-sulfamethoxazole for 14 days, and the combination for 7 days de-escalated to HD daptomycin for 7 days and de-escalated to trimethoprim-sulfamethoxazole for 7 days. Differences in CFU/g (at 168 and 336 h) were evaluated by analysis of variance (ANOVA) with a Tukey's
post hoc
test. Daptomycin MICs were 4 μg/ml (SA H9749-1, vancomycin-intermediate
Staphylococcus aureus
; R6212, heteroresistant vancomycin-intermediate
Staphylococcus aureus
) and 2 μg/ml (R5599 and R5563). Trimethoprim-sulfamethoxazole MICs were ≤0.06/1.19 μg/ml. HD daptomycin plus trimethoprim-sulfamethoxazole displayed rapid bactericidal activity against SA H9749-1 (at 7 h) and R6212 (at 6 h) and bactericidal activity against R5599 (at 72 h) and R5563 (at 36 h). A ≥8 log
10
CFU/g decrease was observed with HD daptomycin plus trimethoprim-sulfamethoxazole against all strains (at 48 to 144 h), which was maintained with de-escalation to HD daptomycin or trimethoprim-sulfamethoxazole at 336 h. The combination for 14 days and the combination for 7 days de-escalated to HD daptomycin or trimethoprim-sulfamethoxazole was significantly better than daptomycin monotherapy (
P
< 0.05) and trimethoprim-sulfamethoxazole monotherapy (
P
< 0.05) at 168 and 336 h. Combination therapy followed by de-escalation offers a novel bactericidal therapeutic alternative for high-inoculum, serious DNS MRSA infections.
Kinetic and Crystallographic Studies of Extended-Spectrum GES-11, GES-12, and GES-14 β-Lactamases
Authors: Delbrück Heinrich , Bogaerts Pierre , Kupper Michaël B. , Rezende de Castro Roberta , Bennink Sandra , Glupczynski Youri , Galleni Moreno , Hoffmann Kurt M. , Bebrone Carine 
Published: August 2012

ABSTRACT

GES-1 is a class A extended-spectrum β-lactamase conferring resistance to penicillins, narrow- and expanded-spectrum cephalosporins, and ceftazidime. However, GES-1 poorly hydrolyzes aztreonam and cephamycins and exhibits very low
k
cat
values for carbapenems. Twenty-two GES variants have been discovered thus far, differing from each other by 1 to 3 amino acid substitutions that affect substrate specificity. GES-11 possesses a Gly243Ala substitution which seems to confer to this variant an increased activity against aztreonam and ceftazidime. GES-12 differs from GES-11 by a single Thr237Ala substitution, while GES-14 differs from GES-11 by the Gly170Ser mutation, which is known to confer increased carbapenemase activity. GES-11 and GES-12 were kinetically characterized and compared to GES-1 and GES-14. Purified GES-11 and GES-12 showed strong activities against most tested β-lactams, with the exception of temocillin, cefoxitin, and carbapenems. Both variants showed a significantly increased rate of hydrolysis of cefotaxime, ceftazidime, and aztreonam. On the other hand, GES-11 and GES-12 (and GES-14) variants all containing Ala243 exhibited increased susceptibility to classical inhibitors. The crystallographic structures of the GES-11 and GES-14 β-lactamases were solved. The overall structures of GES-11 and GES-14 are similar to that of GES-1. The Gly243Ala substitution caused only subtle local rearrangements, notably in the typical carbapenemase disulfide bond. The active sites of GES-14 and GES-11 are very similar, with the Gly170Ser substitution leading only to the formation of additional hydrogen bonds of the Ser residue with hydrolytic water and the Glu166 residue.
Initial reactions to the Woman's Condom by potential user groups in Shanghai, China
Authors: Coffey Patricia S , Kilbourne-Brook Maggie , Junqing Wu , Yufeng Zhang , Hongxin Zhao , Bin Wen , Na Li , Rui Zhao , Yuyan Li 
Published: August 2012

BackgroundThe Woman's Condom, a second-generation female condom, is currently being manufactured in China by the Shanghai Dahua Medical Apparatus Company. The manufacturer plans to launch the product in China.MethodsA survey and focus group discussions were conducted with 73 women and 57 men from nine potential user groups in the Shanghai area to explore, on the basis of visual inspection of the Woman's Condom and product information, their perceptions and attitudes toward the Woman's Condom and lubricant. The potential user groups were male and female university students, male and female college-educated young people, married women and men, migrant women and men, and women working in the entertainment industry.ResultsFemale condoms were a new concept for almost all study participants. Women (49%) and men (51%) reported that the Woman's Condom would make “some” or a “great” difference in their lives. Participants reported interest in using the Woman's Condom for sexually transmitted infection (STI) (50%) or dual protection (43%) rather than for pregnancy prevention alone (33%). Findings highlighted comfort, partner approval and lubricant as possible concerns.ConclusionsProduct introduction activities should be oriented toward the most likely early adopter groups (i.e. university students, college-educated young people, migrant women and women working in the entertainment industry). Lack of interest in using the new device by married women/men and migrant men may indicate that they do not perceive a need for a dual protection product since they are already using a contraceptive method and/or do not perceive themselves at risk of STIs.
Physical and temporal factors controlling the development of near-surface ground ice at Illisarvik, western Arctic coast, Canada
Authors: O’Neill H. Brendan , Burn C.R. 
Published: August 2012

Near-surface permafrost was sampled in summer 2010 at 26 sites in the Illisarvik drained-lake basin and nine sites in the surrounding tundra on Richards Island, NWT, to investigate the growth of segregated near-surface ground ice. Permafrost and ground ice have developed in the lake basin since drainage in 1978. The lake bed soils are predominantly silts of varying moisture and organic-matter contents, with sandier soils near the lake margins. Excess-ice contents in the basin were also variable, and ice enrichment was observed to a maximum depth of 60 cm below the 2010 permafrost table. Shrub-covered, wet areas had the highest mean excess-ice content in the top 50 cm of permafrost (10%), while grassy, dryer areas (4%) and poorly vegetated marginal areas (<1%) were less enriched with ice. Site wetness was the most important variable associated with near-surface excess-ice content in the lake basin. Silt content was a secondary variable. Mean excess-ice content in the top 50 cm of permafrost at tundra sites (25%) was much greater than in the basin, with ice enrichment to greater depths, likely a result of the time available for permafrost aggradation since the early Holocene climatic optimum.
Effect of short-term exercise training on intramyocellular lipid content
Authors: Bajpeyi Sudip , Reed Melissa A. , Molskness Sara , Newton Christopher , Tanner Charles J. , McCartney Jennifer S. , Houmard Joseph A. 
Published: August 2012

The purpose of this study was to investigate the influence of exercise training on intramyocellular lipid (IMCL) content and test the hypothesis that the effect of endurance-oriented exercise training on IMCL is dependent on characteristics of the population studied. Lean (N = 11, body mass index (BMI) = 22.2 ± 0.7 kg·m–2), obese (N = 14, BMI = 38.8 ± 1.7 kg·m–2), and type 2 diabetic (N = 9, BMI = 35.5 ± 2.5 kg·m–2) participants were examined before and after 10 consecutive days of endurance-oriented (60 min·day–1 at ~70% [Formula: see text]O2peak) exercise training. IMCL and muscle glycogen were measured by Oil-Red-O and periodic acid – Schiff staining, respectively. The results indicated that IMCL was elevated (p < 0.05) in the obese and diabetic groups compared with the lean subjects prior to training. After training, IMCL content decreased (–35%) in the participants with type 2 diabetes; there were no changes in IMCL in the lean or obese groups. Muscle glycogen content was lower in the diabetic subjects than in the lean subjects both before and after training. These data indicate that changes in IMCL with exercise training do not exhibit a universal response but rather depend on the metabolic status of the population studied.
Examination of the Moxus Modular Metabolic System by the Douglas-bag technique
Authors: Medbø Jon Ingulf , Mamen Asgeir , Beltrami Fernando G. 
Published: August 2012

The purpose of this study was to examine the performance of the Moxus Modular Metabolic System from AEI Technologies, Inc. using the Douglas-bag method as reference. To achieve this, eight moderately trained subjects cycled for 5 min at constant powers from 50 to 300 W in increments of 50 W. The O2uptake was measured simultaneously by both systems during the last minute of each stage. The O2uptake reported by the Moxus system was 83 ± 78 mL·min–1higher (mean ± SD; ≈3%, +62 µmol·s–1, P < 0.001) than that reported by the Douglas-bag method; the bias varied by ≈2% between the subjects. The higher O2uptake of the Moxus system was a consequence of 1.4% ± 3.0% higher reported ventilation and 2% ± 3% higher reported O2extraction per volume of air breathed. The respiratory exchange ratio (R value) reported by the Moxus system rose proportionally to that of the Douglas-bag method and was 1% ± 2% higher for the range examined (0.75–1.10). Repeated tests of the maximal O2uptake showed a variability (coefficient of variation) of 2.5%. The study concluded that measurements by the Moxus system showed some bias and residual variation and, in addition, some systematic differences between the subjects in the O2uptake. The R value was reported quite accurately with moderate random error. Although there were some computer software and hardware instability problems that need to be solved, the Moxus system worked quite well and provided data more reliable than those of most commercial instruments.
HEART DEPOLARIZATION VECTOR LOCUS CARDIOGRAM AND ITS CLINICAL DIAGNOSTIC APPLICATIONS
Authors: NAGENTHIRAN T. , GHISTA DHANJOO N. , PRASAD V. RAMANAN 
Published: August 2012

This study demonstrates the development of the heart depolarization vector locus cardiogram (HPVLC, from limb leads and a modified Einthoven's triangle) as a diagnostic measure of the left ventricular depolarization strength. Our work involves the reconstruction of the "equivalent heart electrical-activity vector (HAV)" for the QRS complex from limb leads voltages of a sample ECG recording, and plotting the progression of the cardiac vector during the QRS complex. A realistic visualization of the progression of the equivalent-dipole HAV during the QRS complex is possible by staging the HPVLC of the QRS complex from the onset of the QRS till the end of the depolarization stage. This can enable the characterization of the HPVLC by means of an analytical function. By studying the HPVLC for various electro-cardiological disorders, it is possible to determine the ranges of the analytical function's parameters for normal and disordered electro-cardiological states, for diagnostic purpose. We have seen that the monitored ECG is theoretically derived from HAV components on the sides of the Einthoven triangle. Nevertheless, in cardiac practice, the monitored ECG is employed in diagnosis of heart diseases. From the ECG, we can obtain the heart rate, and therefrom the heart rate variability, which too has diagnostic applications. Many nonlinear methods have been proposed to analyze ECG and HRV for detection of cardiac abnormalities, using linear and nonlinear methods. Herein, we have shown how HRV signal can be analyzed in terms of four recurrence quantification analysis (RQA) features, which are then combined into an Integrated Index to enable better separation of normal and diabetic subjects.
Special projects grants awarded
Authors: Baldwin Doug 
Published: August 2012

SIGCSE received 15 Special Projects grant proposals for the May 2012 funding cycle. The Special Projects Committee is pleased to announce that the following four grants have been awarded:
Anthony Allevato and Steve Edwards, Virginia Tech, "Pythy---A Cloud-Based IDE for Novice Python Programmers" (http://pythy.cs.vt.edu/). This project will develop a Web-based environment in which novice programmers can write and run Python programs and access documentation and tutorials. This environment reduces the barriers students often face if they have to install development tools on their own computers.
A Prospective PCR-Based Screening for the EML4-ALK Oncogene in Non–Small Cell Lung Cancer
Authors: Soda Manabu , Isobe Kazutoshi , Inoue Akira , Maemondo Makoto , Oizumi Satoshi , Fujita Yuka , Gemma Akihiko , Yamashita Yoshihiro , Ueno Toshihide , Takeuchi Kengo , Choi Young Lim , Miyazawa Hitoshi , Tanaka Tomoaki , Hagiwara Koichi , Mano Hiroyuki ,   for the North-East Japan Study Group and the ALK Lung Cancer Study Group
Published: August 2012

Abstract
Purpose: EML4-ALK is a lung cancer oncogene, and ALK inhibitors show marked therapeutic efficacy for tumors harboring this fusion gene. It remains unsettled, however, how the fusion gene should be detected in specimens other than formalin-fixed, paraffin-embedded tissue. We here tested whether reverse transcription PCR (RT-PCR)-based detection of EML4-ALK is a sensitive and reliable approach.
Experimental Design: We developed a multiplex RT-PCR system to capture ALK fusion transcripts and applied this technique to our prospective, nationwide cohort of non–small cell lung cancer (NSCLC) in Japan.
Results: During February to December 2009, we collected 916 specimens from 853 patients, quality filtering of which yielded 808 specimens of primary NSCLC from 754 individuals. Screening for EML4-ALK and KIF5B-ALK with our RT-PCR system identified EML4-ALK transcripts in 36 samples (4.46%) from 32 individuals (4.24%). The RT-PCR products were detected in specimens including bronchial washing fluid (n = 11), tumor biopsy (n = 8), resected tumor (n = 7), pleural effusion (n = 5), sputum (n = 4), and metastatic lymph node (n = 1). The results of RT-PCR were concordant with those of sensitive immunohistochemistry with ALK antibodies.
Conclusions: Multiplex RT-PCR was confirmed to be a reliable technique for detection of ALK fusion transcripts. We propose that diagnostic tools for EML4-ALK should be selected in a manner dependent on the available specimen types. FISH and sensitive immunohistochemistry should be applied to formalin-fixed, paraffin-embedded tissue, but multiplex RT-PCR is appropriate for other specimen types. Clin Cancer Res; 18(20); 5682–9. ©2012 AACR.
Gene Expression Signature–Based Prognostic Risk Score in Patients with Primary Central Nervous System Lymphoma
Authors: Kawaguchi Atsushi , Iwadate Yasuo , Komohara Yoshihiro , Sano Masakazu , Kajiwara Koji , Yajima Naoki , Tsuchiya Naoto , Homma Jumpei , Aoki Hiroshi , Kobayashi Tsutomu , Sakai Yuko , Hondoh Hiroaki , Fujii Yukihiko , Kakuma Tatsuyuki , Yamanaka Ryuya 
Published: August 2012

Abstract
Purpose: Better understanding of the underlying biology of primary central nervous system lymphomas (PCNSL) is critical for the development of early detection strategies, molecular markers, and new therapeutics. This study aimed to define genes associated with survival of patients with PCNSL.
Experimental Design: Expression profiling was conducted on 32 PCNSLs. A gene classifier was developed using the random survival forests model. On the basis of this, prognosis prediction score (PPS) using immunohistochemical analysis is also developed and validated in another data set with 43 PCNSLs.
Results: We identified 23 genes in which expressions were strongly and consistently related to patient survival. A PPS was developed for overall survival (OS) using a univariate Cox model. Survival analyses using the selected 23-gene classifiers revealed a prognostic value for high-dose methotrexate (HD-MTX) and HD-MTX–containing polychemotherapy regimen–treated patients. Patients predicted to have good outcomes by the PPS showed significantly longer survival than those with poor predicted outcomes (P &lt; 0.0001). PPS using immunohistochemical analysis is also significant in test (P = 0.0004) and validation data set (P = 0.0281). The gene-based predictor was an independent prognostic factor in a multivariate model that included clinical risk stratification (P &lt; 0.0001). Among the genes, BRCA1 protein expressions were most strongly associated with patient survival.
Conclusion: We have identified gene expression signatures that can accurately predict survival in patients with PCNSL. These predictive genes should be useful as molecular biomarkers and they could provide novel targets for therapeutic interventions. Clin Cancer Res; 18(20); 5672–81. ©2012 AACR.
Characterization of Model Spread in PMIP2 Mid-Holocene Simulations of the African Monsoon
Authors: Zheng Weipeng , Braconnot Pascale 
Published: August 2012

Abstract
Simulations of the West African monsoon (WAM) for the present-day climate (0 ka) and the mid-Holocene (6 ka) using the coupled models from the Paleoclimate Modelling Intercomparison Project phase 2 (PMIP2) are assessed in this study. The authors first compare the ensemble simulations with modern observations and proxy estimates of past precipitation, showing that the PMIP2 model median captures the basic features of the WAM for 0 ka and the changes at 6 ka, despite systematic biases in the preindustrial (PI) simulations and underestimates of the northward extent and intensity of precipitation changes.
The model spread is then discussed based on a classification of the monsoonal convective regimes for a subset of seven coupled models. Two major categories of model are defined based on their differences in simulating deep and moderate convective regimes in the PI simulations. Changes in precipitation at 6 ka are dominated by changes in the large-scale dynamics for most of the PMIP2 models and are characterized by a shift in the monsoonal circulation toward deeper convective regimes. Consequently, changes in the total precipitation at 6 ka depend on the changes in convective regimes and the characteristics of these regimes in the PI simulations. The results indicate that systematic model biases in simulating the radiation and heat fluxes could explain the damping of the meridional temperature gradient over West Africa and thereby the underestimation of precipitation in the Sahel–Sahara region.
A Historical Perspective on Southeastern Australian Rainfall since 1865 Using the Instrumental Record
Authors: Timbal B. , Fawcett R. 
Published: August 2012

Abstract
The instrumental record for rainfall across Australia is regarded as being sufficiently reliable to produce national monthly gridded rainfall analyses from 1900 onward. Prior to 1900, the rainfall gauge network is much sparser. The possibility of using those nineteenth-century observations that do exist to construct an estimate of rainfall across the southeastern part of Australia (SEA) is explored by constructing a network based on 11 locations comprising either single observing sites or composites of nearby observing sites with long continuous records. It is shown that, during the period 1900–2010, the monthly rainfall reconstruction based on this network captures 98% of the variability of SEA monthly average rainfall. This network, which extends back to 1865, provides a useful view of the Federation Drought, making a comparison possible with other long-term droughts observed in SEA, around the time of the Second World War and the Millennium Drought from 1997 to 2009. A comparison of these three historical low-rainfall periods was conducted using the drought–depth–duration criteria: the ongoing decline in southeastern Australia is seen as being notably worse than the previous two historical droughts. The network also provides an insight into the decadal variability of SEA rainfall in the later part of the nineteenth century; it includes a high peak in the 1870s comparable to similar wet decadal peaks in the 1950s and 1970s. The implications of this longer perspective on the decadal variability in southeastern Australia in light of the current understanding of the ongoing rainfall deficit are discussed.