Dimension Reduction via Colour Refinement

Colour refinement is a basic algorithmic routine for graph isomorphism testing, appearing as a subroutine in almost all practical isomorphism solvers. It partitions the vertices of a graph into "colour classes" in such a way that all vertices in the same colour class have the same number of neighbours in every colour class. Tinhofer (Disc. App. Math., 1991), Ramana, Scheinerman, and Ullman (Disc. Math., 1994) and Godsil (Lin. Alg. and its App., 1997) established a tight correspondence between colour refinement and fractional isomorphisms of graphs, which are solutions to the LP relaxation of a natural ILP formulation of graph isomorphism. We introduce a version of colour refinement for matrices and extend existing quasilinear algorithms for computing the colour classes. Then we generalise the correspondence between colour refinement and fractional automorphisms and develop a theory of fractional automorphisms and isomorphisms of matrices. We apply our results to reduce the dimensions of systems of linear equations and linear programs. Specifically, we show that any given LP L can efficiently be transformed into a (potentially) smaller LP L' whose number of variables and constraints is the number of colour classes of the colour refinement algorithm, applied to a matrix associated with the LP. The transformation is such that we can easily (by a linear mapping) map both feasible and optimal solutions back and forth between the two LPs. We demonstrate empirically that colour refinement can indeed greatly reduce the cost of solving linear programs

Sustained effectiveness and cost-effectiveness of Counselling for Alcohol Problems, a brief psychological treatment for harmful drinking in men, delivered by lay counsellors in primary care: 12-month followup of a randomised controlled trial

Background Counselling for Alcohol Problems (CAP), a brief intervention delivered by lay counsellors, enhanced remission and abstinence over 3 months among primary care male attendees with harmful drinking in a setting in India. We evaluate the sustainability of the effects after treatment termination, the cost-effectiveness of CAP over 12 months, and the effects of the hypothesized mediator of ‘readiness to change’ on clinical outcomes. Methods and Findings Male primary care attenders aged 18-65 screening with harmful drinking on the Alcohol Use Disorders Identification Test (AUDIT) were randomized to either CAP plus Enhanced Usual Care (EUC) (n=188) or EUC alone (n=189), of whom 89% completed assessments at 3 months and 84% at 12 months. Primary outcomes were remission and daily standard ethanol consumed in the past 14 days; and the proposed mediating variable was readiness to change at 3 months. CAP participants maintained the gains they showed at the end of treatment through the 12-month follow-up, with the proportion with remission (AUDIT<8: 54.3% vs 31.9%; aPR 1.71 [95% CI 1.32-2.22]; p<0.001) and abstinence in the past 14 days (45.1% vs 26.4%; aOR 1.92 [95% CI 1.19-3.10]; p=0.008) being significantly higher in the EUC plus CAP group than in the EUC alone group. They also fared better on secondary outcomes including recovery (AUDIT<8 at 3 and 12 months: 27.4% vs 15.1%; aPR 1.90 [95% CI 1.21-3.0]; p=0.006); and percent of days abstinent (mean% [SD] 71.0 [38.2] vs 55. 0 [39.8]; AMD 16.1 [95% CI 7.1-25.0]; p=0.001). The intervention effect for remission was higher at 12 months compared to that at 3 months (aPR 1·50 [95% CI 1·09–2·07]. There was no evidence of an intervention effect on Patient Health Questionnaire-9 score, suicidal behaviour, percentage days of heavy drinking, Short Inventory of Problems score, WHO Disability Assessment Schedule II score, days unable to work, and perpetration of intimate partner violence. Economic analyses indicated that CAP was dominant over EUC alone, with lower costs and better outcomes; uncertainty analysis showed a 99% chance of CAP being cost-effective per remission achieved from a health system perspective, using a willingness to pay threshold equivalent to one month’s wages for an unskilled manual worker in Goa. Readiness to change levels at 3 months mediated the effects of CAP on mean daily drinking at 12 months (Indirect effect -6.014, 95% CI -13.99- to -0.046). Serious adverse events were infrequent and prevalence was similar by arm. The methodological limitations of this trial are the susceptibility of self-reported drinking to social desirability bias, the modest participation rates of eligible patients, and examination of mediation effects of only one mediator and in only half of our sample. Conclusions CAP’s superiority over EUC at the end of treatment was largely stable over time and mediated by readiness to change. CAP provides better outcomes at lower costs from a societal perspective

Pregabalin for the treatment of postoperative pain: Results from three controlled trials using different surgical models

Conclusion: There were no significant differences between pregabalin and placebo with respect to the primary pain intensity measure in each of the three clinical trials. These studies encompass a large dataset (1,233 patients in total), and their results should be considered when assessing pregabalin’s effectiveness in postoperative pain. Further studies are required to determine the potential pain-reducing benefit of pregabalin in the postoperative setting

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Bullhorn Hernia: A Rare Traumatic Abdominal Wall Hernia

Traumatic abdominal wall hernia (TAWH) is rare despite the high prevalence of blunt abdominal trauma. Bullhorn hernia occurs as a result of a direct blow to the abdominal wall by the horn of a bull, which disrupts the muscles and fascia and leads to hernia formation. We report a rare case of bullhorn TAWH in a 70‑year‑old patient who presented with swelling at the left lumbar region. The patient was managed by immediate surgical intervention. A surgeon must have high index of suspicion for the diagnosis of this condition as missed hernias in this setting pose a high risk of strangulation and gangrene.Keywords: Blunt abdominal trauma, colostomy, mesh repair, primary repai

Identification of genes preferentially expressed in wheat egg cells and zygotes

Wheat genes differentially expressed in the egg cell before and after fertilization were identified. The data support zygotic gene activation before the first cell division in wheat. To have an insight into fertilization-induced gene expression, cDNA libraries have been prepared from isolated wheat egg cells and one-celled zygotes. Two-hundred and twenty-six egg cell and 253 zygote-expressed EST sequences were determined. Most of the represented transcripts were detected in the wheat egg cell or zygote transcriptome at the first time. Expression analysis of fourteen of the identified genes and three controls was carried out by real-time quantitative PCR. The preferential expression of all investigated genes in the female gametophyte-derived samples (egg cells, zygotes, two-celled proembryos, and basal ovule parts with synergids) in comparison to the anthers, and the leaves were verified. Three genes with putative signaling/regulatory functions were expressed at a low level in the egg cell but exhibited increased (2-to-33-fold) relative expression in the zygote and the proembryo. Genes with high EST abundance in cDNA libraries exhibited strong expression in the egg cell and the zygote, while the ones coding for unknown or hypothetical proteins exhibited differential expression patterns with preferential transcript accumulation in egg cells and/or zygotes. The obtained data support the activation of the zygotic genome before the first cell division in wheat

A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity.

Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance. Comparative proteomics of cornified envelopes (CEs) from prenatal KtyI(-/-) and KtyII(-/-)(K8) mice demonstrates that absence of KIF causes dysregulation of many CE constituents, including downregulation of desmoglein 1. Despite persistence of loricrin expression and upregulation of many Nrf2 targets, including CE components Sprr2d and Sprr2h, extensive barrier defects persist, identifying keratins as essential CE scaffolds. Furthermore, we show that KIFs control mitochondrial lipid composition and activity in a cell-intrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation