On Secure Workflow Decentralisation on the Internet

Decentralised workflow management systems are a new research area, where most work to-date has focused on the system's overall architecture. As little attention has been given to the security aspects in such systems, we follow a security driven approach, and consider, from the perspective of available security building blocks, how security can be implemented and what new opportunities are presented when empowering the decentralised environment with modern distributed security protocols. Our research is motivated by a more general question of how to combine the positive enablers that email exchange enjoys, with the general benefits of workflow systems, and more specifically with the benefits that can be introduced in a decentralised environment. This aims to equip email users with a set of tools to manage the semantics of a message exchange, contents, participants and their roles in the exchange in an environment that provides inherent assurances of security and privacy. This work is based on a survey of contemporary distributed security protocols, and considers how these protocols could be used in implementing a distributed workflow management system with decentralised control . We review a set of these protocols, focusing on the required message sequences in reviewing the protocols, and discuss how these security protocols provide the foundations for implementing core control-flow, data, and resource patterns in a distributed workflow environment

Identifying adolescents at highest risk of ART non-adherence, using the World Health Organization-endorsed HEADSS and HEADSS+ checklists

Brief tools are necessary to identify adolescents at greatest risk for ART non-adherence. From the WHO’s HEADSS/HEADSS+ adolescent wellbeing checklists, we identify constructs strongly associated with non-adherence (validated with viral load). We conducted interviews and collected clinical records from a 3-year cohort of 1046 adolescents living with HIV from 52 South African government facilities. We used least absolute shrinkage and selection operator variable selection approach with a generalized linear mixed model. HEADSS constructs most predictive were: violence exposure (aOR 1.97, CI 1.61; 2.42, p < 0.001), depression (aOR 1.71, CI 1.42; 2.07, p < 0.001) and being sexually active (aOR 1.80, CI 1.41; 2.28, p < 0.001). Risk of non-adherence rose from 20.4% with none, to 55.6% with all three. HEADSS+ constructs were: medication side effects (aOR 2.27, CI 1.82; 2.81, p < 0.001), low social support (aOR 1.97, CI 1.60; 2.43, p < 0.001) and non-disclosure to parents (aOR 2.53, CI 1.91; 3.53, p < 0.001). Risk of non-adherence rose from 21.6% with none, to 71.8% with all three. Screening within established checklists can improve identification of adolescents needing increased support. Adolescent HIV services need to include side-effect management, violence prevention, mental health and sexual and reproductive health

DNA methylation signature of passive smoke exposure is less pronounced than active smoking: the Understanding Society study

Introduction The extent of the biological impact of passive smoke exposure is unclear. We sought to investigate the association between passive smoke exposure and DNA methylation, which could serve as a biomarker of health risk. Materials and methods We derived passive smoke exposure from self-reported questionnaire data among smoking and non-smoking partners of participants enrolled in the UK Household Longitudinal Study ‘Understanding Society’ (n=769). We performed an epigenome-wide association study (EWAS) of passive smoke exposure with DNA methylation in peripheral blood measured using the Illumina Infinium Methylation EPIC array. Results No CpG sites surpassed the epigenome-wide significance threshold of p<5.97 × 10−8 in relation to partner smoking, compared with 10 CpG sites identified in relation to own smoking. However, 10 CpG sites surpassed a less stringent threshold of p<1 × 10−5 in a model of partner smoking adjusted for own smoking (model 1), 7 CpG sites in a model of partner smoking restricted to non-smokers (model 2) and 16 CpGs in a model restricted to regular smokers (model 3). In addition, there was evidence for an interaction between own smoking status and partners’ smoking status on DNA methylation levels at the majority of CpG sites identified in models 2 and 3. There was a clear lack of enrichment for previously identified smoking signals in the EWAS of passive smoke exposure compared with the EWAS of own smoking. Conclusion The DNA methylation signature associated with passive smoke exposure is much less pronounced than that of own smoking, with no positive findings for ‘expected’ signals. It is unlikely that changes to DNA methylation serve as an important mechanism underlying the health risks of passive smoke exposure

Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

<p>Abstract</p> <p>Background</p> <p>The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM) have not been defined completely. We have shown in conscious dogs with DM that: <it>1</it>) baseline coronary blood flow (CBF) was significantly decreased, <it>2</it>) endothelium-dependent (ACh) coronary vasodilation was impaired, and <it>3</it>) reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes.</p> <p>Methods</p> <p>Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv) over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4).</p> <p>Results</p> <p>The array data revealed that 797 genes were differentially expressed (P < 0.01; fold change of at least ±2). 150 genes were expressed at significantly greater levels in diabetic dogs and 647 were significantly reduced. There was no change in eNOS mRNA. There was up regulation of some components of the NADPH oxidase subunits (gp91 by 2.2 fold, P < 0.03), and down-regulation of SOD1 (3 fold, P < 0.001) and decrease (4 - 40 fold) in a large number of genes encoding mitochondrial enzymes. In addition, there was down-regulation of Ca²⁺cycling genes (ryanodine receptor; SERCA2 Calcium ATPase), structural proteins (actin alpha). Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase), which were markedly down regulated.</p> <p>Conclusion</p> <p>our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.</p

Medical Pluralism Predicts Non-ART Use among Parents in Need of ART: A Community Survey in KwaZulu-Natal, South Africa

Despite documented common use of traditional healers and efforts to scale up antiretroviral treatment (ART) in sub-Saharan Africa, evidence on whether medical pluralism predicts ART use is inconclusive and restricted to clinic settings. This study quantitatively assesses whether medical pluralism predicts ART use among parents in need of ART in South Africa. 2,477 parents or primary caregivers of children were interviewed in HIV-endemic communities of KwaZulu-Natal. Analysis used multiple logistic regression on a subsample of 435 respondents in need of ART, who reported either medical pluralism (24.6 %) or exclusive public healthcare use (75.4 %). Of 435 parents needing ART, 60.7 % reported ART use. Medical pluralism emerged as a persistent negative predictor of ART utilization among those needing it (AOR [95 % CI] = .556 [.344 - .899], p = .017). Use of traditional healthcare services by those who need ART may act as a barrier to treatment access. Effective intersectoral collaboration at community level is urgently needed

Genetic Knock-Down of HDAC7 Does Not Ameliorate Disease Pathogenesis in the R6/2 Mouse Model of Huntington's Disease

Huntington's disease (HD) is an inherited, progressive neurological disorder caused by a CAG/polyglutamine repeat expansion, for which there is no effective disease modifying therapy. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression. Administration of histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) have consistently shown therapeutic potential in models of HD, at least partly through increasing the association of acetylated histones with down-regulated genes and by correcting mRNA abnormalities. The HDAC enzyme through which SAHA mediates its beneficial effects in the R6/2 mouse model of HD is not known. Therefore, we have embarked on a series of genetic studies to uncover the HDAC target that is relevant to therapeutic development for HD. HDAC7 is of interest in this context because SAHA has been shown to decrease HDAC7 expression in cell culture systems in addition to inhibiting enzyme activity. After confirming that expression levels of Hdac7 are decreased in the brains of wild type and R6/2 mice after SAHA administration, we performed a genetic cross to determine whether genetic reduction of Hdac7 would alleviate phenotypes in the R6/2 mice. We found no improvement in a number of physiological or behavioral phenotypes. Similarly, the dysregulated expression levels of a number of genes of interest were not improved suggesting that reduction in Hdac7 does not alleviate the R6/2 HD-related transcriptional dysregulation. Therefore, we conclude that the beneficial effects of HDAC inhibitors are not predominantly mediated through the inhibition of HDAC7

Speech Communication

Contains table of contents for Part V, table of contents for Section 1, reports on six research projects and a list of publications.C.J. Lebel FellowshipDennis Klatt Memorial FundNational Institutes of Health Grant R01-DC00075National Institutes of Health Grant R01-DC01291National Institutes of Health Grant R01-DC01925National Institutes of Health Grant R01-DC02125National Institutes of Health Grant R01-DC02978National Institutes of Health Grant R01-DC03007National Institutes of Health Grant R29-DC02525National Institutes of Health Grant F32-DC00194National Institutes of Health Grant F32-DC00205National Institutes of Health Grant T32-DC00038National Science Foundation Grant IRI 89-05249National Science Foundation Grant IRI 93-14967National Science Foundation Grant INT 94-2114