Comparative genomics and understanding of microbial biology.

The sequences of close to 30 microbial genomes have been completed during the past 5 years, and the sequences of more than 100 genomes should be completed in the next 2 to 4 years. Soon, completed microbial genome sequences will represent a collection of >200,000 predicted coding sequences. While analysis of a single genome provides tremendous biological insights on any given organism, comparative analysis of multiple genomes provides substantially more information on the physiology and evolution of microbial species and expands our ability to better assign putative function to predicted coding sequences

Social Competence Treatment after Traumatic Brain Injury: A Multicenter, Randomized, Controlled Trial of Interactive Group Treatment versus Non-Interactive Treatment

Objective To evaluate the effectiveness of a replicable group treatment program for improving social competence after traumatic brain injury (TBI). Design Multicenter randomized controlled trial comparing two methods of conducting a social competency skills program, an interactive group format versus a classroom lecture. Setting Community and Veteran rehabilitation centers. Participants 179 civilian, military, and veteran adults with TBI and social competence difficulties, at least 6 months post-injury. Experimental Intervention Thirteen weekly group interactive sessions (1.5 hours) with structured and facilitated group interactions to improve social competence. Alternative (Control) Intervention Thirteen traditional classroom sessions using the same curriculum with brief supplemental individual sessions but without structured group interaction. Primary Outcome Measure Profile of Pragmatic Impairment in Communication (PPIC), an objective behavioral rating of social communication impairments following TBI. Secondary Outcomes LaTrobe Communication Questionnaire (LCQ), Goal Attainment Scale (GAS), Satisfaction with Life Scale (SWLS), Post-Traumatic Stress Disorder Checklist – (PCL-C), Brief Symptom Inventory 18 (BSI-18), Scale of Perceived Social Self Efficacy (PSSE). Results Social competence goals (GAS) were achieved and maintained for most participants regardless of treatment method. Significant improvements in the primary outcome (PPIC) and two of the secondary outcomes (LCQ and BSI) were seen immediately post-treatment and at 3 months post-treatment in the AT arm only, however these improvements were not significantly different between the GIST and AT arms. Similar trends were observed for PSSE and PCL-C. Conclusions Social competence skills improved for persons with TBI in both treatment conditions. The group interactive format was not found to be a superior method of treatment delivery in this study

The Future Evolution of White Dwarf Stars Through Baryon Decay and Time Varying Gravitational Constant

Motivated by the possibility that the fundamental ``constants'' of nature could vary with time, this paper considers the long term evolution of white dwarf stars under the combined action of proton decay and variations in the gravitational constant. White dwarfs are thus used as a theoretical laboratory to study the effects of possible time variations, especially their implications for the future history of the universe. More specifically, we consider the gravitational constant $G$ to vary according to the parametric relation $G = G_0 (1 + t/t_\ast)^{-p}$, where the time scale $t_\ast$ is the same order as the proton lifetime. We then study the long term fate and evolution of white dwarf stars. This treatment begins when proton decay dominates the stellar luminosity, and ends when the star becomes optically thin to its internal radiation.Comment: 12 pages, 10 figures, accepted to Astrophysics and Space Scienc

REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States.

BackgroundSome trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States.MethodsREDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points.ResultsA total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; P=0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; P=0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; P=0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; P=0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; P=0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; P=0.004); for all-cause mortality in the US versus non-US patients, Pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort.ConclusionsWhereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01492361

Comparison of Lateral Flow to Other Pregnancy Determination Methods in Order to Determine Accuracy of Pregnancy Status in Beef Cattle Pre and Postpartum

Study Description: Blood samples were collected from six different Bos taurus herds between day 27 and 285 of gestation (heifers n = 1,205 and cows n = 1,539). Blood samples to determine PAG clearance interval were collected weekly postpartum for up to 12 weeks (heifers n = 418 and cows n = 657). Serum was tested using the lateral flow test and were read by two technicians who were blind to pregnancy status. Level of agreement between the tests were determined by Pearson’s correlation coefficients and Kappa scores. The MIXED procedure of SAS was used to evaluate the effect of dpp and age (heifers or cows) on postpartum test results. There was a positive correlation between transrectal ultrasonography and the lateral flow test (r2 = 0.71; P \u3c 0.01), and agreement between the two tests was very good (Kappa = 0.84). Of the animals that were diagnosed nonpregnant by transrectal ultrasonography, 5.61% were called pregnant by the lateral flow test. Of the animals diagnosed pregnant by transrectal ultrasonography, 2.00% were called not pregnant by the lateral flow test. Thus, a 92.38% agreement occurred between the two methods. For postpartum samples, there was no effect (P = 0.21) of age, but there was an effect of dpp (P \u3c 0.01) and a tendency for a dpp by age interaction (P = 0.06). All animals were still considered pregnant from the previous pregnancy through 35 dpp (100 ± 2.58%). The percentage of females receiving a false positive test result further decreased with time postpartum, by 77 dpp there were 13.72 ± 3.16% of the females positive for pregnancy and at 84 dpp there were 4.11 ± 4.39% positive for pregnancy detection

The Optical Alignment System of the ATLAS Muon Spectrometer Endcaps

The muon spectrometer of the ATLAS detector at the Large Hadron Collider (LHC) at CERN consists of over a thousand muon precision chambers, arranged in three concentrical cylinders in the barrel region, and in four wheels in each of the two endcaps. The endcap wheels are located between 7m and 22m from the interaction point, and have diameters between 13m and 24m. Muon chambers are equipped with a complex on-line optical alignment system to monitor their positions and deformations during ATLAS data-taking. We describe the layout of the endcap part of the alignment system and the design and calibration of the optical sensors, as well as the various software components. About 1% of the system has been subjected to performance tests in the H8 beam line at CERN, and results of these tests are discussed. The installation and commissioning of the full system in the ATLAS cavern is well underway, and results from approximately half of the system indicate that we will reach the ambitious goal of a 40mu alignment accuracy, required for reconstructing final-state muons at the highest expected energies

Proton Motive Force-Dependent Hoechst 33342 Transport by the ABC Transporter LmrA of Lactococcus lactis

The fluorescent compound Hoechst 33342 is a substrate for many multidrug resistance (MDR) transporters and is widely used to characterize their transport activity. We have constructed mutants of the adenosine triphosphate (ATP) binding cassette (ABC)-type MDR transporter LmrA of Lactococcus lactis that are defective in ATP hydrolysis. These mutants and wild-type LmrA exhibited an atypical behavior in the Hoechst 33342 transport assay. In membrane vesicles, Hoechst 33342 transport was shown to be independent of the ATPase activity of LmrA, and it was not inhibited by orthovanadate but sensitive to uncouplers that collapse the proton gradient and to N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. In contrast, transport of Hoechst 33342 by the homologous, heterodimeric MDR transporter LmrCD showed a normal ATP dependence and was insensitive to uncouplers of the proton gradient. With intact cells, expression of LmrA resulted in an increased rate of Hoechst 33342 influx while LmrCD caused a decrease in the rate of Hoechst 33342 influx. Cellular toxicity assays using a triple knockout strain, i.e., L. lactis ΔlmrA ΔlmrCD, demonstrate that expression of LmrCD protects cells against the growth inhibitory effects of Hoechst 33342, while in the presence of LmrA, cells are more susceptible to Hoechst 33342. Our data demonstrate that the LmrA-mediated Hoechst 33342 transport in membrane vesicles is influenced by the transmembrane pH gradient due to a pH-dependent partitioning of Hoechst 33342 into the membrane.

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes

Performance study of GPUs in real-time trigger applications for HEP experiments

Graphical Processing Units (GPUs) have evolved into highly parallel, multi-threaded, multicore powerful processors with high memory bandwidth. GPUs are used in a variety of intensive computing applications. The combination of highly parallel architecture and high memory bandwidth makes GPUs a potentially promising technology for effective real-time processing for High Energy Physics (HEP) experiments. However, not much is known of their performance in real-time applications that require low latency, such as the trigger for HEP experiments. We describe an R and D project with the goal to study the performance of GPU technology for possible low latency applications, performing basic operations as well as some more advanced HEP lower-level trigger algorithms (such as fast tracking or jet finding). We present some preliminary results on timing measurements, comparing the performance of a CPU versus a GPU with NVIDIA's CUDA general-purpose parallel computing architecture, carried out at CDF's Level-2 trigger test stand. These studies will provide performance benchmarks for future studies to investigate the potential and limitations of GPUs for real-time applications in HEP experiments