PP-Wave / CFT_2 Duality

We investigate the pp-wave limit of the AdS_3\times S^3\times K3 compactification of Type IIB string theory from the point of view of the dual Sym_N(K3) CFT. It is proposed that a fundamental string in this pp-wave geometry is dual to the c=6 effective string of the Sym_N(K3) CFT, with the string bits of the latter being composed of twist operators. The massive fundamental string oscillators correspond to certain twisted Virasoro generators in the effective string. It is shown that both the ground states and the genus expansion parameter (at least in the orbifold limit of the CFT) coincide. Surprisingly the latter scales like J^2/N rather than the J^4/N^2 which might have been expected. We demonstrate a leading-order agreement between the pp-wave and CFT particle spectra. For a degenerate special case (one NS 5-brane) an intriguing complete agreement is found.Comment: JHEP3 LaTeX, 20 pages; discussion of WZW levels clarified, reference adde

The prevalence and characteristics of moderate- to high-risk regulated and unregulated substance use among patients admitted to four public hospitals in Tshwane, South Africa

BACKGROUND. Alcohol, tobacco and unregulated substance use contributes to the global burden of disease. Admission to hospital provides an opportunity to screen patients for substance use and offer interventions. OBJECTIVES. To determine the prevalence and nature of substance use and treatment as well as interest in harm reduction among inpatients from four hospitals in the City of Tshwane, South Africa. METHODS. In a cross-sectional study, sociodemographic and substance use data were collected from 401 patients using the World Health Organization’s Alcohol, Smoking and Substance Involvement Screening Test. Demographic characteristics were analysed using descriptive statistics. Bivariate and multivariate analyses of moderate- to high-risk tobacco and unregulated substance use in relation to demographic characteristics were also done. RESULTS. Most patients were South African (88%) and black African (79%), over half were female (57%), and they were relatively young (median age 38 years). Most (82%) lived in formal housing. Over half (56%) had completed high school, and 33% were formally employed. Bivariate analysis found substance use-related admission to be higher where scores for tobacco and unregulated substance use were moderate to high (13% v. 0.3%, p<0.05). A notably higher (p<0.1) proportion of participants with no/low tobacco and unregulated substance use had completed high school, were employed and were cohabiting/married compared with those with moderate to high scores. Across the hospitals, 32% (129/401) of the participants had moderate- to high-risk use of at least one substance: tobacco (28%, 111/401), alcohol (10%, 40/401), cannabis (7%, 28/401), opioids (2%, 9/401) and sedatives (2%, 9/401). Of these 129 participants, 10% had accessed professional help, many (67%, 78/129) wanted to learn more about harm reduction, and most (84%, 108/129) said that they were willing to participate in a community-based harm reduction programme. Multivariate analysis found moderate- to high-risk tobacco and unregulated substance use to be positively associated with male sex (adjusted odds ratio (aOR) 7.9, 95% confidence interval (CI) 2.9 - 21.5), age <38 years (aOR 3.3, 95% CI 1.2 - 8.9), moderate- to high-risk alcohol use (aOR 3.1, 95% CI 1.1 - 8.4; p=0.027) and being admitted to Tshwane District Hospital (aOR 3.6, 95% CI 1.1 - 12.2). It was negatively associated with employment (aOR 0.2, 95% CI 0.1 - 0.6). CONCLUSIONS. Moderate- to high-risk substance use is an undetected, unattended comorbidity in the hospital setting in Tshwane, particularly among young, single, unemployed men. Clinicians should identify and respond to this need. Further research is required on the implementation of in-hospital substance use screening and treatment interventions.The City of Tshwanehttp://www.samj.org.zaam2020Family Medicin

UV Finite Brane Decay

The decay of an unstable D-brane via closed string emission and open string pair production is considered in subcritical string theory with a spacelike linear dilaton. The decay rate is given by the imaginary part of the annulus, which has ambiguities corresponding to the choices of incoming closed and open string vacua. An exact expression for the full annulus diagram is computed with a natural choice of incoming vacua. It is found that the ultraviolet divergences present in critical string theory in both of these processes are absent for any nonzero spacelike dilaton. Implications for the vexing issue of the tachyon dust are discussed.Comment: 21 pages, 3 figures, minor changes, changed to JHEP styl

Origin of strange metallic phase in cuprate superconductors

The origin of strange metallic phase is shown to exist due to these two conditions---(i) the electrons are strongly interacting such that there are no band and Mott-Hubbard gaps, and (ii) the electronic energy levels are crossed in such a way that there is an electronic energy gap between two energy levels associated to two different wave functions. The theory is also exploited to explain (i) the upward- and downward-shifts in the $T$-linear resistivity curves, and (ii) the spectral weight transfer observed in the soft X-ray absorption spectroscopic measurements of the La-Sr-Cu-O Mott insulator.Comment: To be published in J. Supercond. Nov. Mag

Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a significant effect on stromal cells, mediated through a druggable MIF-CD74 axis. These data highlight the complex interplay between alterations in the MPN clone and activation of stromal cells and indicate that Gli1 represents a promising therapeutic target in MPNs, particularly that Hh signaling is dispensable for normal hematopoiesis.</p

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the fi

Comparative Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography and Positron Emission Tomography in the Characterisation of Solitary Pulmonary Nodules

Abstract Introduction: Dynamic contrast-enhanced computed tomography (DCE-CT) and Positron Emission Tomography/Computed Tomography (PET/CT) have a high reported accuracy for the diagnosis of malignancy in solitary pulmonary nodules. The aim of this study was to compare the accuracy and cost-effectiveness of these. Methods: In this prospective multicentre trial, 380 participants with a solitary pulmonary nodule (8-30mm) and no recent history of malignancy underwent DCE-CT and PET/CT. All patients underwent either biopsy with histological diagnosis or completed CT follow-up. Primary outcome measures were sensitivity, specificity, and overall diagnostic accuracy for PET/CT and DCE-CT. Costs and cost-effectiveness were estimated from a healthcare provider perspective using a decision-model. Results: 312 participants (47% female, 68.1±9.0 years) completed the study, with 61% rate of malignancy at 2 years. The sensitivity, specificity, positive predictive value and negative predictive values for DCE-CT were 95.3% [95% CI 91.3;97.5], 29.8% [95% CI 22.3;38.4], 68.2% [95% CI 62.4%;73.5%] and 80.0% [95% CI 66.2;89.1] respectively, and for PET/CT were 79.1% [95% CI 72.7;84.2], 81.8% [95% CI 74.0;87.7], 87.3%[95% CI 81.5;91.5) and 71·2% [95% CI 63.2;78.1]. The area under the receiver operator characteristic curve (AUROC) for DCE-CT and PET/CT was 0.62 [95%CI 0.58;0.67] and 0.80 [95%CI 0.76;0.85] respectively (p<0.001). Combined results significantly increased diagnostic accuracy over PET/CT alone (AUROC=0.90 [95%CI 0.86;0.93], p<0.001). DCE-CT was preferred when the willingness to pay per incremental cost per correctly treated malignancy was below £9000. Above £15500 a combined approach was preferred. Conclusions: PET/CT has a superior diagnostic accuracy to DCE-CT for the diagnosis of solitary pulmonary nodules. Combining both techniques improves the diagnostic accuracy over either test alone and could be cost-effective. (Clinical trials.gov - NCT02013063)

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe