Generally Covariant Actions for Multiple D-branes

We develop a formalism that allows us to write actions for multiple D-branes with manifest general covariance. While the matrix coordinates of the D-branes have a complicated transformation law under coordinate transformations, we find that these may be promoted to (redundant) matrix fields on the transverse space with a simple covariant transformation law. Using these fields, we define a covariant distribution function (a matrix generalization of the delta function which describes the location of a single brane). The final actions take the form of an integral over the curved space of a scalar single-trace action built from the covariant matrix fields, tensors involving the metric, and the covariant distribution function. For diagonal matrices, the integral localizes to the positions of the individual branes, giving N copies of the single-brane action.Comment: 34 pages, LaTeX. v2: comments and refs adde

A critical appreciation of intangible resources in PharmaNutrition

Background: Organizations in knowledge-intensive industries such as the field of PharmaNutrition benefit from a critical consideration of intangible resources for innovation performance and competitive advantage. Effective management of these resources, however, is complicated due to difficulties in their identification, appropriation, application, and evaluation. As a consequence, knowledge-intensive organizations are at risk of suboptimal exploitation of their most important value drivers. Methods: The literature on organizational intangible resources was reviewed as part of an ongoing investigation into effective management of intangible resources in the PharmaNutrition-specific context. Results: Although high-level dimensions of intangible resources are recognized across industries, the identity and relevance of various lower-level components are heterogenous and dependent on organization's unique situational attributes. Despite the existence of historical, industry-sourced tick-the-box lists presented here, an analysis of industry-specific characteristics of intangible resources and mechanisms to appropriate their value is warranted to enable practitioners to innovate effectively and efficiently. Conclusions: This editorial aims to put the topics of intangible resources and their appropriability on the agenda, and invites scholars and practitioners to contribute to the advancement of our understanding regarding these topics through an online survey

ZOBOV: a parameter-free void-finding algorithm

ZOBOV (ZOnes Bordering On Voidness) is an algorithm that finds density depressions in a set of points, without any free parameters, or assumptions about shape. It uses the Voronoi tessellation to estimate densities, which it uses to find both voids and subvoids. It also measures probabilities that each void or subvoid arises from Poisson fluctuations. This paper describes the ZOBOV algorithm, and the results from its application to the dark-matter particles in a region of the Millennium Simulation. Additionally, the paper points out an interesting high-density peak in the probability distribution of dark-matter particle densities.Comment: 10 pages, 8 figures, MNRAS, accepted. Added explanatory figures, and better edge-detection methods. ZOBOV code available at http://www.ifa.hawaii.edu/~neyrinck/vobo

Genome-wide estimation of transcript concentrations from spotted cDNA microarray data

A method providing absolute transcript concentrations from spotted microarray intensity data is presented. Number of transcripts per µg total RNA, mRNA or per cell, are obtained for each gene, enabling comparisons of transcript levels within and between tissues. The method is based on Bayesian statistical modelling incorporating available information about the experiment from target preparation to image analysis, leading to realistically large confidence intervals for estimated concentrations. The method was validated in experiments using transcripts at known concentrations, showing accuracy and reproducibility of estimated concentrations, which were also in excellent agreement with results from quantitative real-time PCR. We determined the concentration for 10 157 genes in cervix cancers and a pool of cancer cell lines and found values in the range of 10(5)–10(10) transcripts per µg total RNA. The precision of our estimates was sufficiently high to detect significant concentration differences between two tumours and between different genes within the same tumour, comparisons that are not possible with standard intensity ratios. Our method can be used to explore the regulation of pathways and to develop individualized therapies, based on absolute transcript concentrations. It can be applied broadly, facilitating the construction of the transcriptome, continuously updating it by integrating future data

Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis:Results from the Norfolk Arthritis Register

Objectives: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years’ follow-up in a cohort of patients with inflammatory polyarthritis (IP).  Methods: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.  Results: 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.  Conclusions: Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA

Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer : A Randomized, Double-blind, Placebo-Controlled, Phase II Study

Purpose Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer. Experimental Design: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics). Results: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [ HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota. Conclusions: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.Peer reviewe

Liraglutide and sitagliptin have no effect on intestinal microbiota composition : A 12-week randomized placebo-controlled trial in adults with type 2 diabetes

Aim: Preclinical data suggest that treatment with either glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors could change the intestinal microbiome and thereby contribute to their beneficial (cardio)metabolic effects. Therefore, our study aimed to investigate the effects of these agents on microbiota composition in adults with type 2 diabetes (T2D). Methods: A total of 51 adults with T2D (mean +/- SD: age 62.8 +/- 6.9 years, BMI 31.8 +/- 4.1 kg/m(2), HbA(1c) 7.3 +/- 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial. Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks. Faecal samples were collected at baseline and at 12 weeks after the start of the intervention. Microbiota analyses were performed by 16S rRNA gene-sequencing analysis. Bile acids were measured in faeces and plasma. Results: Liraglutide decreased HbA(1c) by 1.3% (95% CI: -1.7 to -0.9) and tended to reduce body weight (-1.7 kg, 95% CI: -3.6 to 0.3), but increased faecal secondary bile acid deoxycholic acid. Sitagliptin lowered HbA(1c) by 0.8% (95% CI: -1.4 to -0.4) while body weight remained stable (-0.8 kg, 95% CI: -2.7 to 1.0), but increased faecal levels of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid. However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters. Conclusion: These data suggest that the beneficial effects of liraglutide and sitagliptin on glucose metabolism, body weight and bile acids, when used as add-on therapies to metformin or sulphonylureas, are not linked to changes in the intestinal microbiota (NCT01744236). (C) 2021 The Authors. Published by Elsevier Masson SAS.Peer reviewe

Coherent Backscattering of light in a magnetic field

This paper describes how coherent backscattering is altered by an external magnetic field. In the theory presented, magneto-optical effects occur inside Mie scatterers embedded in a non-magnetic medium. Unlike previous theories based on point-like scatterers, the decrease of coherent backscattering is obtained in leading order of the magnetic field using rigorous Mie theory. This decrease is strongly enhanced in the proximity of resonances, which cause the path length of the wave inside a scatterer to be increased. Also presented is a novel analysis of the shape of the backscattering cone in a magnetic field.Comment: 27 pages, 5 figures, Revtex, to appear in Phys. Rev.

Testing models for molecular gas formation in galaxies: hydrostatic pressure or gas and dust shielding?

Stars in galaxies form in giant molecular clouds that coalesce when the atomic hydrogen is converted into molecules. There are currently two dominant models for what property of the galactic disk determines its molecular fraction: either hydrostatic pressure driven by the gravity of gas and stars, or a combination of gas column density and metallicity. To assess the validity of these models, we compare theoretical predictions to the observed atomic gas content of low-metallicity dwarf galaxies with high stellar densities. The extreme conditions found in these systems are optimal to distinguish the two models, otherwise degenerate in nearby spirals. Locally, on scales <100 pc, we find that the state of the interstellar medium is mostly sensitive to the gas column density and metallicity rather than hydrostatic pressure. On larger scales where the average stellar density is considerably lower, both pressure and shielding models reproduce the observations, even at low metallicity. We conclude that models based on gas and dust shielding more closely describe the process of molecular formation, especially at the high resolution that can be achieved in modern galaxy simulations or with future radio/millimeter arrays.Comment: 20 pages, 12 figures. Accepted for publication in Ap