A direct solver with O(N) complexity for variable coefficient elliptic PDEs discretized via a high-order composite spectral collocation method

A numerical method for solving elliptic PDEs with variable coefficients on two-dimensional domains is presented. The method is based on high-order composite spectral approximations and is designed for problems with smooth solutions. The resulting system of linear equations is solved using a direct (as opposed to iterative) solver that has optimal O(N) complexity for all stages of the computation when applied to problems with non-oscillatory solutions such as the Laplace and the Stokes equations. Numerical examples demonstrate that the scheme is capable of computing solutions with relative accuracy of $10^{-10}$ or better, even for challenging problems such as highly oscillatory Helmholtz problems and convection-dominated convection diffusion equations. In terms of speed, it is demonstrated that a problem with a non-oscillatory solution that was discretized using $10^{8}$ nodes was solved in 115 minutes on a personal work-station with two quad-core 3.3GHz CPUs. Since the solver is direct, and the "solution operator" fits in RAM, any solves beyond the first are very fast. In the example with $10^{8}$ unknowns, solves require only 30 seconds.Comment: arXiv admin note: text overlap with arXiv:1302.599

Epstein-Barr Virus (EBV) nuclear antigen 3C inhibits expression of COBLL1 and the ADAM28-ADAMDEC1 locus via interaction with the histone lysine demethylase KDM2B

Epstein-Barr virus nuclear antigen 3C (EBNA3C) is a well-defined repressor of host gene expression in B cells transformed by Epstein-Barr virus (EBV) that cooperates with various cellular factors. It is established that EBNA3C interacts with the cellular factor RBPJ (RBP-Jκ or CBF1) through two distinct motifs: the TFGC motif, also called the homology domain (HD) motif, and the VWTP motif. In this study, we investigated the role of each motif in EBNA3C transcriptional repression activity by using two novel recombinant viruses with single RBPJ interaction motifs mutated (EBNA3C HDmut and EBNA3C W227S). Infection of primary B cells with either of these recombinant EBVs led to the successful establishment of lymphoblastoid cell lines (LCLs). Gene expression analysis showed that full repression of EBNA3C target genes is not achieved by EBNA3C HDmut compared to that with EBNA3C W227S or the EBNA3C wild type (WT). Focusing on the well-characterized EBNA3C-repressed genes COBLL1, ADAM28, and ADAMDEC1, we investigated the mechanism of EBNA3C-mediated transcriptional repression. Chromatin immunoprecipitation (ChIP) analysis indicated that EBNA3C HDmut is still able to recruit Polycomb proteins BMI1 and SUZ12 to COBLL1 as efficiently as EBNA3C WT does, leading to the full deposition of the repressive histone mark H3K27me3. However, we found that the activation-associated chromatin mark H3K4me3 is highly enriched at EBNA3C target genes in LCLs expressing EBNA3C HDmut. We show here that EBNA3C interacts with the histone lysine demethylase KDM2B and that this interaction is important for H3K4me3 removal and for the EBNA3C-mediated repression of COBLL1 and the ADAM28-ADAMDEC1 locus. IMPORTANCE EBV is a virus associated with human cancers and is well known for its ability to transform B lymphocytes into continuously proliferating lymphoblastoid cell lines. EBNA3C is considered an oncoprotein and has been shown to be essential for B cell transformation by EBV. EBNA3C is well characterized as a viral transcription factor, but very little is known about its mechanisms of action. In the present study, we demonstrate that removal of the activating histone mark H3K4me3 and deposition of the repressive mark H3K27me3 by EBNA3C on COBLL1 are achieved by at least two distinct mechanisms. Furthermore, we discovered that EBNA3C interacts with the lysine demethylase KDM2B and that this interaction is important for its transcriptional repressive function. The findings in this study provide new insights into the mechanism used by the oncoprotein EBNA3C to repress cellular target genes

Health risk appraisal in older people 7: long-acting benzodiazepine use in community-dwelling older adults in London: is it related to physical or psychological factors?

To investigate whether the use of long-acting benzodiazepines, in individuals aged 65 and over is mediated by physical or psychological factors. Long-acting benzodiazepine consumption among older people has implications for mortality, morbidity and cost-effective prescribing. Two models explain benzodiazepine use in this age group, one linked to physical illness and disability and one to psychological factors. Secondary analysis of baseline data from a study of 1059 community-dwelling non-disabled people aged 65 years and over recruited from three general practices in London. For this analysis, use of long-acting benzodiazepines was defined as any self-reported use of diazepam or nitrazepam in the last four weeks. Associations between demographic factors, health service use, and physical and psychological characteristics and benzodiazepine use were investigated. The prevalence of benzodiazepine use in this sample was 3.3% (35/1059). In univariate analyses, benzodiazepine use was associated with female gender, low income, high consultation rates, physical factors (medication for arthritis or joint pain, polypharmacy, difficulties in instrumental activities of daily living, recent pain) and psychological factors (poor self-perceived health, social isolation, and symptoms of anxiety or agitation). In a multivariate logistic regression analysis only two factors retained statistically significant independent associations with benzodiazepine use: receiving only the state pension (OR=4.0, 95% CI: 1.70, 9.80) and pain in the past four weeks (OR=3.79, 95% CI: 1.36, 10.54)

Maladaptive schemas as a potential mechanism through which irrational beliefs relate to psychological distress in athletes

© 2019 Elsevier Ltd Objectives: The psychological wellbeing of athletes, in particular the concept of psychological distress, is receiving growing research attention. Irrational beliefs as proposed in Rational Emotive Behaviour Therapy (REBT) have been shown to be positively related to the psychological distress of athletes, but the mechanisms by which irrational beliefs predict psychological distress remain unclear. The role of maladaptive schemas, as proposed in Schema Therapy (ST), in the relationship between irrational beliefs and psychological distress has not yet been studied, despite the conceptual similarities between REBT and ST. Design and method: Participants were self-selected triathletes (n = 124), duathletes (n = 9), swimmers (n = 7), cyclists (n = 17) and runners (n = 57). A single timepoint cross-sectional study design was used to investigate simple mediation models using the PROCESS macro. Results: Results revealed that maladaptive schemas fully mediated the positive relationship between irrational beliefs and symptoms of anxiety, and depression (psychological distress). Conclusions: These findings suggest that maladaptive schemas are a potential mechanism through which irrational beliefs predict psychological distress. Results may help practitioners begin to understand how REBT and ST may be applied in tandem for the benefit of greater athlete psychological wellbeing

Relationships between Social Resources and Healthful Behaviors across the Age Spectrum

Background. We examined cross-sectional relationships of social resources with health behaviors in adults ages 18–93 years. Methods. Baseline data from a 2009 risk behavior intervention trial were used to measure social resources, physical activity, and fruit and vegetable intake in 2,440 adults. To evaluate associations overall and within 4 age groups (18–34, 35–49, 50–64, and 65–93 y), we used multivariable regression. Results. Mean (SD) age was 49.4 (15) years, physical activity was 346 (304) minutes/week, and fruit and vegetable intake was 3.4 (2.4) servings/day. Mean social resource score was 1.2 (0–4 scale) in 18–34 year olds, 1.1 in all other age groups (P = 0.04). In multivariable models, for each one-point increment in social resource score, the odds ratio for getting 150–959 minutes of physical activity/wk (compared to <150 min/wk) was 3.7 (95% CI 3.0–4.6). Each one-point increment in score was also associated with 29% (95% CI: 23–35%) more servings of fruit and vegetables. We did not observe effect modification by age group. Conclusions:. Although younger adults reported slightly higher resources than older adults, the magnitude of association between social resources and healthful behaviors did not differ between them

Drugs of Abuse Can Entrain Circadian Rhythms

Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse

Story in health and social care

This paper offers a brief consideration of how narrative, in the form of people‟s own stories, potentially figures in health and social care provision as part of the impulse towards patient-centred care. The rise of the epistemological legitimacy of patients‟ stories is sketched here. The paper draws upon relevant literature and original writing to consider the ways in which stories can mislead as well as illuminate the process of making individual treatment care plans