Area distribution of two-dimensional random walks on a square lattice

The algebraic area probability distribution of closed planar random walks of length N on a square lattice is considered. The generating function for the distribution satisfies a recurrence relation in which the combinatorics is encoded. A particular case generalizes the q-binomial theorem to the case of three addends. The distribution fits the L\'evy probability distribution for Brownian curves with its first-order 1/N correction quite well, even for N rather small.Comment: 8 pages, LaTeX 2e. Reformulated in terms of q-commutator

Moduli stabilization and uplifting with dynamically generated F-terms

We use the F-term dynamical supersymmetry breaking models with metastable vacua in order to uplift the vacuum energy in the KKLT moduli stabilization scenario. The main advantage compared to earlier proposals is the manifest supersymmetric treatment and the natural coexistence of a TeV gravitino mass with a zero cosmological constant. We argue that it is generically difficult to avoid anti de-Sitter supersymmetric minima, however the tunneling rate from the metastable vacuum with zero vacuum energy towards them can be very suppressed. We briefly comment on the properties of the induced soft terms in the observable sector.Comment: 18 pages, no figures Comments and one reference adde

The development of a short measure of physical function for knee OA KOOS-Physical Function Shortform (KOOS-PS) – an OARSI/OMERACT initiative

SummaryObjectiveTo develop a short measure of physical function for knee osteoarthritis (OA) using multi-national data from individuals with varying degrees of severity of knee OA.MethodsRasch analysis, based on the partial credit model, was conducted on Knee injury and Osteoarthritis Outcome Score and Western Ontario McMaster Universities' Osteoarthritis Index data from individuals with knee OA, ranging from community to pre-total knee replacement samples from five countries. Fit of the data to the Rasch model was evaluated by overall model fit and item-level fit statistics (χ2, size of residual, F-test). Invariance across age, gender and country was evaluated. Unidimensionality was evaluated by factor analysis of residuals. The derived short measure was further tested for fit through re-analyses in individual sub-samples. A nomogram converting raw summed scores to Rasch-derived interval scores was developed.ResultsThirteen data sets were included (n=2145), with an age range of 26–95 years, and a male/female ratio of 1:1.4. The final model included seven of the original 22 items. From easiest to most difficult, the items (logit) were as follows: rising from bed (1.366), putting on socks/stockings (1.109), rising from sitting (0.537), bending to the floor (0.433), twisting/pivoting on injured knee (−0.861), kneeling (−1.292) and squatting (−1.292). Sub-sample analyses confirmed findings.ConclusionBased on the use of accepted Rasch-based measurement methods and the compliment of countries, languages and OA severity represented in this study, our seven item short measure of physical function for knee OA is likely generalizable and widely applicable. This measure has potential for use as the function component in an OA severity scoring system

International nifedipine trial on anti-atherosclerotic therapy (INTACT) - methodologic implications and results of a coronary angiographic follow-up study using computer-assisted film analysis

Animal experiments demonstrated a significant suppressive effect of various calcium channel blockers on the formation of atherosclerotic lesions. Therefore, a prospective, placebo-controlled, randomized, double blind multicenter study was performed to investigate the inhibitory influence of the calcium channel blocker nifedipine (80 mg/day) on the progression of coronary artery disease in man. Study endpoints were changes of coronary morphology documented by coronary angiography with particular respect to the formation of new coronary stenoses. In 348 out of 425 patients included in the study, coronary angiograms were repeated after three years. The angiograms were standardized by induction of a maximal coronary vasodilation with high doses of nitrates and by using absolutely identical angiographic projections. Quantitative analysis of coronary cineangiograms was performed with the computer-assisted contour detection system CAAS. Parameters were mean and minimal diameter of all segments and minimal stenosis diameter, percent diameter stenosis, length and plaque area of all stenoses. Continuous intake of study medication was registered in 282 patients, 134 on nifedipine and 148 patients on placebo. In these patients, a total of 3808 coronary segments with 893 stenoses (≥ 20% diameter reduction in at least one angiographic projection) were compared on the baseline and follow-up cineangiograms. The changes in all angiographic parameters analyzed averaged over all patients by considering all angiographic projections analyzed, indicated significant progression of the disease (p < 0.006). The average changes in all parameters were even about three times more profound, when in the individual patients only the respective projections indicating the maximal changes were considered for the calculation (p < 0.001). However, with neither of these two analysis modes, the differences in progression between the treatment groups were statistically significant. In the follow-up angiograms, a total of 196 new coronary lesions (185 stenoses, 11 occlusions) were found at previously normal arterial sites. In patients on nifedipine, an average of only 0.58 new lesions per patient were detected versus 0,80 lesions per patient on placebo (-27%; p=0.031). INTACT is the first prospective angiographic trial on the progression of coronary artery disease using computer-assisted quantitative coronary angiography in such a high number of patients. All parameters analyzed indicated significant progression of coronary artery sclerosis. Nifedipine had no influen

Brain Radiation Information Data Exchange (BRIDE): Integration of experimental data from low-dose ionising radiation research for pathway discovery

Background: The underlying molecular processes representing stress responses to low-dose ionising radiation (LDIR) in mammals are just beginning to be understood. In particular, LDIR effects on the brain and their possible association with neurodegenerative disease are currently being explored using omics technologies. Results: We describe a light-weight approach for the storage, analysis and distribution of relevant LDIR omics datasets. The data integration platform, called BRIDE, contains information from the literature as well as experimental information from transcriptomics and proteomics studies. It deploys a hybrid, distributed solution using both local storage and cloud technology. Conclusions: BRIDE can act as a knowledge broker for LDIR researchers, to facilitate molecular research on the systems biology of LDIR response in mammals. Its flexible design can capture a range of experimental information for genomics, epigenomics, transcriptomics, and proteomics. The data collection is available at:

Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: a 31P MRS study

Background: Impaired homeostasis of hepatic ATP has been associated with NAFLD. An intravenous fructose infusion has been shown to be an effective challenge to monitor the depletion and subsequent recovery of hepatic ATP reserves using 31P MRS. Aims: The purpose of this study was to evaluate the effects of an oral rather than intravenous fructose challenge on hepatic ATP reserves in healthy subjects. Methods: Self-reported healthy males were recruited. Following an overnight fast, baseline liver glycogen and lipid levels were measured using Magnetic Resonance Spectroscopy (MRS). Immediately after consuming a 500 ml 75 g fructose drink (1275 kJ) subjects were scanned continuously for 90 min to acquire dynamic 31P MRS measurements of liver ATP reserves. Results: A significant effect on ATP reserves was observed across the time course (P < 0.05). Mean ATP levels reached a minimum at 50 min which was markedly lower than baseline (80 ± 17% baseline, P < 0.05). Subsequently, mean values tended to rise but did not reach statistical significance above minimum. The time to minimum ATP levels across subjects was negatively correlated with BMI (R2 ¼ 0.74, P < 0.005). Rates of ATP recovery were not significantly correlated with BMI or liver fat levels, but were negatively correlated with baseline glycogen levels (R2 ¼ 0.7, P < 0.05). Conclusions: Depletion of ATP reserves can be measured non-invasively following an oral fructose challenge using 31P

Monitoring of microbial dynamics in a drinking water distribution system using the culture-free, user-friendly, MYcrobiota platform

Drinking water utilities currently rely on a range of microbiological detection techniques to evaluate the quality of their drinking water (DW). However, microbiota profiling using culture-free 16S rRNA gene next-generation sequencing (NGS) provides an opportunity for improved monitoring of the microbial ecology and quality of DW. Here, we evaluated the utility of a previously validated microbiota profiling platform (MYcrobiota) to investigate the microbial dynamics of a full-scale, non-chlorinated DW distribution system (DWDS). In contrast to conventional methods, we observed spatial and temporal bacterial genus changes (expressed as operational taxonomic units - OTUs) within the DWDS. Further, a small subset of bacterial OTUs dominated with abundances that shifted across the length of the DWDS, and were particularly affected by a post-disinfection step. We also found seasonal variation in OTUs within the DWDS and that many OTUs could not be identified, even though MYcrobiota is specifically designed to reduce potential PCR sequencing artefacts. This suggests that our current knowledge about the microbial ecology of DW communities is limited. Our findings demonstrate that the user-friendly MYcrobiota platform facilitates culture-free, standardized microbial dynamics monitoring and has the capacity to facilitate the introduction of microbiota profiling into the management of drinking water quality

Haplotype reference consortium panel: Practical implications of imputations with large reference panels

Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 × 10-61), particularly for suggestive variants. Both meta-analyses were performed in the same sample size, yet we found eight genome-wide significant loci in the HRC-based meta-analysis versus seven genome-wide significant loci in the 1000GP-based meta-analysis. This study provides supporting evidence of the new avenues for gene discovery and fine mapping that the HRC imputation panel offers

Generalized Contour Dynamics: A Review

Contour dynamics is a computational technique to solve for the motion of vortices in incompressible inviscid flow. It is a Lagrangian technique in which the motion of contours is followed, and the velocity field moving the contours can be computed as integrals along the contours. Its best-known examples are in two dimensions, for which the vorticity between contours is taken to be constant and the vortices are vortex patches, and in axisymmetric flow for which the vorticity varies linearly with distance from the axis of symmetry. This review discusses generalizations that incorporate additional physics, in particular, buoyancy effects and magnetic fields, that take specific forms inside the vortices and preserve the contour dynamics structure. The extra physics can lead to time-dependent vortex sheets on the boundaries, whose evolution must be computed as part of the problem. The non-Boussinesq case, in which density differences can be important, leads to a coupled system for the evolution of both mean interfacial velocity and vortex sheet strength. Helical geometry is also discussed, in which two quantities are materially conserved and whose evolution governs the flow

COVID-19 in health-care workers in three hospitals in the south of the Netherlands:A cross-sectional study

Background: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. Methods: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. Findings: Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. Interpretation: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. Funding: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health