Precision determination of r(0)Lambda((MS)over-bar) from the QCD static energy

We use the recently obtained theoretical expression for the complete QCD static energy at next-to-next-to-next-to leading-logarithmic accuracy to determine r(0)Lambda((MS) over bar) by comparison with available lattice data, where r(0) is the lattice scale and Lambda((MS) over bar) is the QCD scale. We obtain r(0)Lambda((MS) over bar) = 0.622(-0.015)(+0.019) for the zero-flavor case. The procedure we describe can be directly used to obtain r(0)Lambda((MS) over bar) in the unquenched case, when unquenched lattice data for the static energy at short distances becomes available. Using the value of the strong coupling alpha(s) as an input, the unquenched result would provide a determination of the lattice scale r(0).

A Prognostic Score to Identify Low-risk Outpatients with Acute Deep Vein Thrombosis in the Lower Limbs.

BACKGROUND: No prior studies have identified which patients with deep vein thrombosis in the lower limbs are at a low risk for adverse events within the first week of therapy. METHODS: We used data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) to identify patients at low risk for the composite outcome of pulmonary embolism, major bleeding, or death within the first week. We built a prognostic score and compared it with the decision to treat patients at home. RESULTS: As of December 2013, 15,280 outpatients with deep vein thrombosis had been enrolled. Overall, 5164 patients (34%) were treated at home. Of these, 12 (0.23%) had pulmonary embolism, 8 (0.15%) bled, and 4 (0.08%) died. On multivariable analysis, chronic heart failure, recent immobility, recent bleeding, cancer, renal insufficiency, and abnormal platelet count independently predicted the risk for the composite outcome. Among 11,430 patients (75%) considered to be at low risk, 15 (0.13%) suffered pulmonary embolism, 22 (0.19%) bled, and 8 (0.07%) died. The C-statistic was 0.61 (95% confidence interval [CI], 0.57-0.65) for the decision to treat patients at home and 0.76 (95% CI, 0.72-0.79) for the score (P = .003). Net reclassification improvement was 41% (P < .001). Integrated discrimination improvement was 0.034 for the score and 0.015 for the clinical decision (P < .001). CONCLUSIONS: Using 6 easily available variables, we identified outpatients with deep vein thrombosis at low risk for adverse events within the first week. These data may help to safely treat more patients at home. This score, however, should be validated.

Physical activity under confinement and free-living conditions.

The objective of this study was to investigate the relationship between the physical activity (PA) and its related variables under confinement and in free-living conditions in Asian individuals, where no such information presently exists. The subjects consisted of eighty-six Japanese individuals with a mean age of 38+/-12 years. Under confinement in a large respiratory chamber, the energy expenditure (EE) was measured for 24h. In addition, two moderate walking exercises of 30 min each on a horizontal treadmill were assigned. Free-living measurements of 7 days were also performed using a validated accelerometer. The PA level in the chamber (1.47+/-0.11), expressed as a multiple of the basal EE, was lower than that in free-living conditions (1.53+/-0.12) (p<0.001). However, the two values were closely correlated (r=0.744, p<0.001). Conversely, a residual analysis showed a wide variation in the mean difference for both conditions and revealed a significant systematic error (r=-0.548, p<0.001), thus indicating an increased gap with increasing PA levels in free-living conditions. Similar results were obtained following the exclusion of the imposed exercise sessions. In contrast, the daily step counts under both conditions did not show any correlation. The PA level in the chamber (including and excluding imposed walking exercises) is compatible with the PA level in free-living conditions at the group level, although the daily step counts are unrelated. Thus, the PA level in the chamber may provide valuable information to help us achieve a better understanding of human PA in daily life as it is related to behavioral research.

Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia.

Opsismodysplasia (OPS) is a severe autosomal-recessive chondrodysplasia characterized by pre- and postnatal micromelia with extremely short hands and feet. The main radiological features are severe platyspondyly, squared metacarpals, delayed skeletal ossification, and metaphyseal cupping. In order to identify mutations causing OPS, a total of 16 cases (7 terminated pregnancies and 9 postnatal cases) from 10 unrelated families were included in this study. We performed exome sequencing in three cases from three unrelated families and only one gene was found to harbor mutations in all three cases: inositol polyphosphate phosphatase-like 1 (INPPL1). Screening INPPL1 in the remaining cases identified a total of 12 distinct INPPL1 mutations in the 10 families, present at the homozygote state in 7 consanguinous families and at the compound heterozygote state in the 3 remaining families. Most mutations (6/12) resulted in premature stop codons, 2/12 were splice site, and 4/12 were missense mutations located in the catalytic domain, 5-phosphatase. INPPL1 belongs to the inositol-1,4,5-trisphosphate 5-phosphatase family, a family of signal-modulating enzymes that govern a plethora of cellular functions by regulating the levels of specific phosphoinositides. Our finding of INPPL1 mutations in OPS, a severe spondylodysplastic dysplasia with major growth plate disorganization, supports a key and specific role of this enzyme in endochondral ossification.

Socio-demographic and behavioural determinants of weight gain in the Swiss population.

BackgroundIn Switzerland, socio-demographic and behavioural factors are associated with obesity, but no study ever assessed their impact on weight gain using prospective data.MethodsData from 4,469 participants (53.0% women), aged 35 to 75 years at baseline and followed for 5.5 years. Weight gain was considered as a rate (kg/year) or as gaining ¿5 kg during the study period.ResultsRate of weight gain was lower among participants who were older (mean¿±¿standard deviation: 0.46¿±¿0.92, 0.33¿±¿0.88, 0.21¿±¿0.86 and 0.06¿±¿0.74 kg/year in participants aged [35-45[, [45-55[, [55¿65[and [65+ years, respectively, P<0.001); physically active (0.27¿±¿0.82 vs. 0.35¿±¿0.95 kg/year for sedentary, P¿<¿0.005) or living in a couple (0.29¿±¿0.84 vs. 0.35¿±¿0.96 kg/year for living single, P¿<¿0.05), and higher among current smokers (0.41¿±¿0.97, 0.26¿±¿0.84 and 0.29±0.85 kg/year for current, former and never smokers, respectively, p<0.001). These findings were further confirmed by multivariable analysis. Multivariable logistic regression showed that receiving social help, being a current smoker or obese increased the likelihood of gaining ¿5Kg: Odds ratio (OR) and 95% confidence interval (CI) 1.43 (1.16-1.77); 1.63 (1.35-1.95) and 1.95 (1.57-2.43), respectively, while living in couple or being physically active decreased the risk: 0.73 (0.62-0.86) and 0.72 (0.62-0.83), respectively. No association was found between weight gain and gender, being born in Switzerland or education.ConclusionsIn Switzerland, financial difficulties (indicated by receiving social help) and current smoking were associated with increases in body weight over a 5 years follow-up. Living in couple, being older or physically active were protective against weight gain.

Prevalence of measured and reported multimorbidity in a representative sample of the Swiss population.

BACKGROUND: Little is known on the prevalence of multimorbidity (MM) in the general population. We aimed to assess the prevalence of MM using measured or self-reported data in the Swiss population. METHODS: Cross-sectional, population-based study conducted between 2003 and 2006 in the city of Lausanne, Switzerland, and including 3714 participants (1967 women) aged 35 to 75 years. Clinical evaluation was conducted by thoroughly trained nurses or medical assistants and the psychiatric evaluation by psychologists or psychiatrists. For psychiatric conditions, two definitions were used: either based on the participant's statements, or on psychiatric evaluation. MM was defined as presenting ≥2 morbidities out of a list of 27 (self-reported - definition A, or measured - definition B) or as the Functional Comorbidity Index (FCI) using measured data - definition C. RESULTS: The overall prevalence and (95% confidence interval) of MM was 34.8% (33.3%-36.4%), 56.3% (54.6%-57.9%) and 22.7% (21.4%-24.1%) for definitions A, B and C, respectively. Prevalence of MM was higher in women (40.2%, 61.7% and 27.1% for definitions A, B and C, respectively, vs. 28.7%, 50.1% and 17.9% in men, p < 0.001); Swiss nationals (37.1%, 58.8% and 24.8% for definitions A, B and C, respectively, vs. 31.4%, 52.3% and 19.7% in foreigners, all p < 0.001); elderly (>65 years: 67.0%, 70.0% and 36.7% for definitions A, B and C, respectively, vs. 23.6%, 50.2% and 13.8% for participants <45 years, p < 0.001); participants with lower educational level; former smokers and obese participants. Multivariate analysis confirmed most of these associations: odds ratio (95% Confidence interval) 0.55 (0.47-0.64), 0.61 (0.53-0.71) and 0.51 (0.42-0.61) for men relative to women for definitions A, B and C, respectively; 1.27 (1.09-1.49), 1.29 (1.11-1.49) and 1.41 (1.17-1.71) for Swiss nationals relative to foreigners, for definitions A, B and C, respectively. Conversely, no difference was found for educational level for definitions A and B and abdominally obese participants for all definitions. CONCLUSIONS: Prevalence of MM is high in the Lausanne population, and varies according to the definition or the data collection method.

Psychiatric co-morbidities and cardiovascular risk factors in people with lifetime history of epilepsy of an urban community.

OBJECTIVES: Depression has been consistently reported in people with epilepsy. Several studies also suggest a higher burden of cardiovascular diseases. We therefore analysed psychosocial co-morbidity and cardiovascular risk factors in patients with a lifetime history of epilepsy in the PsyCoLaus study, a Swiss urban population-based assessment of mental health and cardiovascular risk factors in adults aged between 35 and 66 years. PATIENTS AND METHODS: Among 3719 participants in the PsyCoLaus study, we retrospectively identified those reporting at least 2 unprovoked seizures, defined as epilepsy. These subjects were compared to all others regarding psychiatric, social, and cardiovascular risk factors data using uni- and multivariable assessments. RESULTS: A significant higher need for social help (p<0.001) represented the only independent difference between 43 subjects with a history of epilepsy and 3676 controls, while a higher prevalence of psychiatric co-morbidities (p=0.015) and a lower prevalent marital status (p=0.01) were only significant on univariate analyses. Depression and cardio-vascular risk factors, as well as educational level and employment, were similar among the groups. CONCLUSIONS: This analysis confirms an increased prevalence of psychosocial burden in subjects with a lifetime history of epilepsy; conversely, we did not find a higher cardiovascular risk. The specific urban and geographical location of our cohort and the age span of the studied population may account for the differences from previous studies.

Roadway Lighting and Safety: Phase II – Monitoring Quality, Durability and Efficiency, November 2011

This Phase II project follows a previous project titled Strategies to Address Nighttime Crashes at Rural, Unsignalized Intersections. Based on the results of the previous study, the Iowa Highway Research Board (IHRB) indicated interest in pursuing further research to address the quality of lighting, rather than just the presence of light, with respect to safety. The research team supplemented the literature review from the previous study, specifically addressing lighting level in terms of measurement, the relationship between light levels and safety, and lamp durability and efficiency. The Center for Transportation Research and Education (CTRE) teamed with a national research leader in roadway lighting, Virginia Tech Transportation Institute (VTTI) to collect the data. An integral instrument to the data collection efforts was the creation of the Roadway Monitoring System (RMS). The RMS allowed the research team to collect lighting data and approach information for each rural intersection identified in the previous phase. After data cleanup, the final data set contained illuminance data for 101 lighted intersections (of 137 lighted intersections in the first study). Data analysis included a robust statistical analysis based on Bayesian techniques. Average illuminance, average glare, and average uniformity ratio values were used to classify quality of lighting at the intersections.

The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification.

The PAR-domain basic leucine zipper (PAR bZip) transcription factors DBP, TEF, and HLF accumulate in a highly circadian manner in several peripheral tissues, including liver and kidney. Mice devoid of all three of these proteins are born at expected Mendelian ratios, but are epilepsy prone, age at an accelerated rate, and die prematurely. In the hope of identifying PAR bZip target genes whose altered expression might contribute to the high morbidity and mortality of PAR bZip triple knockout mice, we compared the liver and kidney transcriptomes of these animals to those of wild-type or heterozygous mutant mice. These experiments revealed that PAR bZip proteins control the expression of many enzymes and regulators involved in detoxification and drug metabolism, such as cytochrome P450 enzymes, carboxylesterases, and constitutive androstane receptor (CAR). Indeed, PAR bZip triple knockout mice are hypersensitive to xenobiotic compounds, and the deficiency in detoxification may contribute to their early aging.

Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner.

BACKGROUND & AIMS: Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. METHODS: We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. RESULTS: The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P = .020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS: The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE.

Mesozoic arc magmatism along the southern Peruvian margin during Gondwana breakup and dispersal

A high-resolution U-Pb zircon geochronological study of plutonic units along the south Peruvian margin between 17 degrees and 18 degrees S allows the integration of the geochemical, geodynamic and tectonic evolution of this part of the Andean margin. This study focuses on the composite Jurassic-early Cretaceous Ilo Batholith that was emplaced along the southern Peruvian coast during two episodes of intrusive magmatism; a first period between 173 and 152 Ma (with a peak in magmatic activity between roughly 168 and 162 Ma) and a second period between 110 and 106 Ma. Emplacement of the Jurassic part of the composite Ilo Batholith shortly post-dated the accumulation of the volcanosedimentary succession it intruded (Chocolate formation), which allows to estimate a subsidence rate for this unit of similar to 3.5 km/Ma. The emplacement of the main peak of Jurassic plutonism of the Ilo Batholith was also closely coeval with widespread and repeated slumping (during deposition of the Cachios Formation) in the back-arc region, suggesting a common causal link between these phenomena, which is discussed in the context of an observed 100 km trenchward arc migration at similar to 175 Ma, and the relation with extensional tectonics that prevailed along the Central Andean margin during Pangaea break-up. (C) 2012 Elsevier B.V. All rights reserved.

Treatment of velopharyngeal insufficiency by autologous fat injection.

Velopharyngeal insufficiency (VPI) is a structural or functional trouble, which causes hypernasal speech. Velopharyngeal flaps, speech therapy and augmentation pharyngoplasty, using different implants, have all been used to address this trouble. We hereby present our results following rhinopharyngeal autologous fat injection in 18 patients with mild velopharyngeal insufficiency (12 soft palate clefts, 4 functional VPI, 2 myopathy). 28 injections were carried out between 2004 and 2007. The degree of hypernasal speech was evaluated pre- and postoperatively by a speech therapist and an ENT specialist and quantified by an acoustic nasometry (Kay Elemetrics). All patients were exhaustively treated with preoperative speech therapy (average, 8 years). The mean value of the nasalance score was 37% preoperatively and 23% postoperatively (p = 0.015). The hypernasality was reduced postoperatively in all patients (1-3 degrees of the Borel-Maisonny score). There were no major complications, two minor complications (one hematoma, one cervical pain). The autologous fat injection is a simple, safe, minimally invasive procedure. It proves to be efficient in cases of mild velopharyngeal insufficiency or after a suboptimal velopharyngoplasty.

Relaxivity of Gd-based contrast agents on X nuclei with long intrinsic relaxation times in aqueous solutions.

The relaxivity of commercially available gadolinium (Gd)-based contrast agents was studied for X-nuclei resonances with long intrinsic relaxation times ranging from 6 s to several hundred seconds. Omniscan in pure 13C formic acid had a relaxivity of 2.9 mM(-1) s(-1), whereas its relaxivity on glutamate C1 and C5 in aqueous solution was approximately 0.5 mM(-1) s(-1). Both relaxivities allow the preparation of solutions with a predetermined short T1 and suggest that in vitro substantial sensitivity gains in their measurement can be achieved. 6Li has a long intrinsic relaxation time, on the order of several minutes, which was strongly affected by the contrast agents. Relaxivity ranged from approximately 0.1 mM(-1) s(-1) for Omniscan to 0.3 for Magnevist, whereas the relaxivity of Gd-DOTP was at 11 mM(-1) s(-1), which is two orders of magnitude higher. Overall, these experiments suggest that the presence of 0.1- to 10-microM contrast agents should be detectable, provided sufficient sensitivity is available, such as that afforded by hyperpolarization, recently introduced to in vivo imaging.

Development of an aggregation assay to screen FimH antagonists.

Alpha-D-mannopyranosides are potent FimH antagonists, which inhibit the adhesion of Escherichia coli to highly mannosylated uroplakin Ia on the urothelium and therefore offer an efficient therapeutic opportunity for the treatment and prevention of urinary tract infection. For the evaluation of the therapeutic potential of FimH antagonists, their effect on the disaggregation of E. coli from Candida albicans and guinea pig erythrocytes (GPE) was studied. The mannose-specific binding of E. coli to yeast cells and erythrocytes is mediated by type 1 pili and can be monitored by aggregometry. Maximal aggregation of C. albicans or GPE to E. coli is reached after 600 s. Then the FimH antagonist was added and disaggregation determined by light transmission over a period of 1400 s. A FimH-deleted mutant of E. coli, which does not induce any aggregation, was used in a control experiment. The activities of FimH antagonists are expressed as IC(50)s, the half maximal inhibitory concentration of the disaggregation potential. n-Heptyl alpha-D-mannopyranoside (1) was used as a reference compound and exhibits an IC(50) of 77.14 microM , whereas methyl alpha-D-mannopyranoside (2) does not lead to any disaggregation at concentrations up to 800 microM. o-Chloro-p-[N-(2-ethoxy-3,4-dioxocyclobut-1-enyl)amino]phenyl alpha-D-mannopyranoside (3) shows a 90-fold and 2-chloro-4-nitrophenyl alpha-D-mannopyranoside (4) a 6-fold increased affinity compared to 1. Finally, 4-nitrophenyl alpha-D-mannopyranoside (5) exhibits an activity similar to 1. As negative control, D-galactose (6) was used. The standardized aggregation assay generates concentration-dependent, reproducible data allowing the evaluation of FimH antagonists according to their potency to inhibit E. coli adherence and can therefore be employed to select candidates for experimental and clinical studies for treatment and prevention of urinary tract infections.

Discovery and molecular characterization of an ambisense densovirus from South American populations of Solenopsis invicta

In an effort to discover viruses as classical biological control agents, a metatranscriptomics/pyrosequencing approach was used to survey native Solenopsis invicta collected exclusively in Argentina. A new virus was discovered with characteristics consistent with the family Parvoviridae, subfamily Densovirinae. The virus, tentatively named Solenopsis invicta densovirus (SiDNV), represents the first DNA virus discovered in ants (Formicidae) and the first densovirus in a hymenopteran insect. The ambisense genome was 5280 nucleotides in length and the termini possessed asymmetrically positioned inverted terminal repeats, formed hairpin loops, and had transcriptional regulatory elements including CAAT and TATA sites. Phylogenetic analysis revealed that SiDNV belongs to a group that includes two other densoviruses found in insects (Acheta domestica densovirus and Planococcus citri densovirus). SiDNV was prevalent in fire ants from Argentina but completely absent in fire ants found in the USA indicating that this virus has potential for biological control of introduced S. invicta.