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Pilot study of antibodies against varicella zoster virus and human immunodeficiency virus in relation to the risk of developing stroke, nested within a rural cohort in Uganda

OBJECTIVE: The risk of stroke rises after episodes of herpes zoster and chickenpox, which are caused by varicella zoster virus (VZV). We conducted a pilot case-control study of stroke, nested within a long-standing cohort in Uganda (the General Population Cohort), to examine antibodies against VZV prior to diagnosis. METHODS: We used stored sera to examine the evolution of IgG and IgM antibodies against VZV among 31 clinically confirmed cases of stroke and 132 matched controls. For each participant, three samples of sera were identified: one each, taken at or near the time of (pseudo)diagnosis, between 5 and 10 years prior to diagnosis and at 15 years prior to diagnosis. RESULTS: All participants had detectable antibodies against VZV, but there were no significant differences between cases and controls in the 15 years prior to diagnosis. As a secondary finding, 16% (5/31) of cases and 6% (8/132) of controls had HIV (OR 3.0; 95% CI 0.8-10.1; P = 0.06). CONCLUSIONS: This is the first prospective study to examine a biological measure of exposure to VZV prior to diagnosis of stroke and although we identified no significant association, in this small pilot, with limited characterisation of cases, we cannot exclude the possibility that the virus is causal for a subset. The impact of HIV on risk of stroke has not been well characterised and warrants further study

Concordance and Mutation

We provide a framework for studying the interplay between concordance and positive mutation and identify some of the basic structures relating the two. The fundamental result in understanding knot concordance is the structure theorem proved by Levine: for n>1 there is an isomorphism phi from the concordance group C_n of knotted (2n-1)-spheres in S^{2n+1} to an algebraically defined group G_{+-}; furthermore, G__{+-} is isomorphic to the infinite direct sum Z^infty direct sum Z_2^infty direct sum Z_4^infty. It was a startling consequence of the work of Casson and Gordon that in the classical case the kernel of phi on C_1 is infinitely generated. Beyond this, little has been discovered about the pair (C_1,phi). In this paper we present a new approach to studying C_1 by introducing a group, M, defined as the quotient of the set of knots by the equivalence relation generated by concordance and positive mutation, with group operation induced by connected sum. We prove there is a factorization of phi, C_1-->M-->G_-. Our main result is that both maps have infinitely generated kernels. Among geometric constructions on classical knots, the most subtle is positive mutation. Positive mutants are indistinguishable using classical abelian knot invariants as well as by such modern invariants as the Jones, Homfly or Kauffman polynomials. Distinguishing positive mutants up to concordance is a far more difficult problem; only one example has been known until now. The results in this paper provide, among other results, the first infinite families of knots that are distinct from their positive mutants, even up to concordance.Comment: Published in Geometry and Topology at http://www.maths.warwick.ac.uk/gt/GTVol5/paper26.abs.htm

Receptor activity-modifying protein dependent and independent activation mechanisms in the coupling of calcitonin gene-related peptide and adrenomedullin receptors to Gs

Calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors are heteromers of the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor, and one of three receptor activity-modifying proteins (RAMPs). How CGRP and AM activate CLR and how this process is modulated by RAMPs is unclear. We have defined how CGRP and AM induce Gs-coupling in CLR-RAMP heteromers by measuring the effect of targeted mutagenesis in the CLR transmembrane domain on cAMP production, modeling the active state conformations of CGRP and AM receptors in complex with the Gs C-terminus and conducting molecular dynamics simulations in an explicitly hydrated lipidic bilayer. The largest effects on receptor signaling were seen with H295A5.40b, I298A5.43b, L302A5.47b, N305A5.50b, L345A6.49b and E348A6.52b, F349A6.53b and H374A7.47b (class B numbering in superscript). Many of these residues are likely to form part of a group in close proximity to the peptide binding site and link to a network of hydrophilic and hydrophobic residues, which undergo rearrangements to facilitate Gs binding. Residues closer to the extracellular loops displayed more pronounced RAMP or ligand-dependent effects. Mutation of H3747.47b to alanine increased AM potency 100-fold in the CGRP receptor. The molecular dynamics simulation showed that TM5 and TM6 pivoted around TM3. The data suggest that hydrophobic interactions are more important for CLR activation than other class B GPCRs, providing new insights into the mechanisms of activation of this class of receptor. Furthermore the data may aid in the understanding of how RAMPs modulate the signaling of other class B GPCRs

Compilation and R-matrix analysis of Big Bang nuclear reaction rates

We use the R-matrix theory to fit low-energy data on nuclear reactions involved in Big Bang nucleosynthesis. A special attention is paid to the rate uncertainties which are evaluated on statistical grounds. We provide S factors and reaction rates in tabular and graphical formats.Comment: 40 pages, accepted for publication at ADNDT, web site at http://pntpm3.ulb.ac.be/bigban

UK women smokers' experiences of an age-progression smoking cessation intervention: Thematic analysis of accounts

Objectives Appearance-related interventions to promote healthy behaviour have been found effective to communicate health risks. The current study aimed to explore women smokers' experiences of age-progression software showing the effects of smoking on the face. Methods A qualitative design was implemented, utilizing both individual interviews and focus groups within a critical realist framework. Fifteen, 19–52 year-old women smokers were administered an age-progression intervention. All participants responded to the intervention, engaged in semi-structured interviews, and were invited back to attend one of three focus groups. Data were analysed using inductive thematic analysis. Results Four main themes were identified: Health versus Appearance, Shock Reaction, Perceived Susceptibility, and Intention to Quit. Participants found the intervention useful, voicing need for a comprehensive approach that includes both appearance and health. Despite increases in appearance-based apps which could diminish impact, women's accounts of shock induced by the aged smoking-morphed images were similar to previous work conducted more than ten years previously. Conclusions The study provides novel insights in how women smokers currently perceive, and react to, an age-progression intervention for smoking cessation. Innovation Findings emphasise the implementation of this intervention type accompanied by health information in a range of patient settings

Universal Rights and Wrongs

This paper argues for the important role of customers as a source of competitive advantage and firm growth, an issue which has been largely neglected in the resource-based view of the firm. It conceptualizes Penrose’s (1959) notion of an ‘inside track’ and illustrates how in-depth knowledge about established customers combines with joint problem-solving activities and the rapid assimilation of new and previously unexploited skills and resources. It is suggested that the inside track represents a distinct and perhaps underestimated way of generating rents and securing long-term growth. This also implies that the sources of sustainable competitive advantage in important respects can be sought in idiosyncratic interfirm relationships rather than within the firm itself

Human Resources and the Resource Based View of the Firm

The resource-based view (RBV) of the firm has influenced the field of strategic human resource management (SHRM) in a number of ways. This paper explores the impact of the RBV on the theoretical and empirical development of SHRM. It explores how the fields of strategy and SHRM are beginning to converge around a number of issues, and proposes a number of implications of this convergence

Training Programmes Can Change Behaviour and Encourage the Cultivation of Over-Harvested Plant Species

Cultivation of wild-harvested plant species has been proposed as a way of reducing over-exploitation of wild populations but lack of technical knowledge is thought to be a barrier preventing people from cultivating a new species. Training programmes are therefore used to increase technical knowledge to encourage people to adopt cultivation. We assessed the impact of a training programme aiming to encourage cultivation of xaté (Chamaedorea ernesti-augusti), an over-harvested palm from Central America. Five years after the training programme ended, we surveyed untrained and trained individuals focusing on four potential predictors of behaviour: technical knowledge, attitudes (what individuals think about a behaviour), subjective norms (what individuals perceive others to think of a behaviour) and perceived behavioural control (self assessment of whether individuals can enact the behaviour successfully). Whilst accounting for socioeconomic variables, we investigate the influence of training upon these behavioural predictors and examine the factors that determine whether people adopt cultivation of a novel species. Those who had been trained had higher levels of technical knowledge about xaté cultivation and higher belief in their ability to cultivate it while training was not associated with differences in attitudes or subjective norms. Technical knowledge and perceived behavioural control (along with socio-economic variables such as forest ownership and age) were predictors of whether individuals cultivate xaté. We suggest that training programmes can have a long lasting effect on individuals and can change behaviour. However, in many situations other barriers to cultivation, such as access to seeds or appropriate markets, will need to be addressed