Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Phase structure of black branes in grand canonical ensemble

This is a companion paper of our previous work [1] where we studied the thermodynamics and phase structure of asymptotically flat black $p$-branes in a cavity in arbitrary dimensions $D$ in a canonical ensemble. In this work we study the thermodynamics and phase structure of the same in a grand canonical ensemble. Since the boundary data in two cases are different (for the grand canonical ensemble boundary potential is fixed instead of the charge as in canonical ensemble) the stability analysis and the phase structure in the two cases are quite different. In particular, we find that there exists an analog of one-variable analysis as in canonical ensemble, which gives the same stability condition as the rather complicated known (but generalized from black holes to the present case) two-variable analysis. When certain condition for the fixed potential is satisfied, the phase structure of charged black $p$-branes is in some sense similar to that of the zero charge black $p$-branes in canonical ensemble up to a certain temperature. The new feature in the present case is that above this temperature, unlike the zero-charge case, the stable brane phase no longer exists and `hot flat space' is the stable phase here. In the grand canonical ensemble there is an analog of Hawking-Page transition, even for the charged black $p$-brane, as opposed to the canonical ensemble. Our study applies to non-dilatonic as well as dilatonic black $p$-branes in $D$ space-time dimensions.Comment: 32 pages, 2 figures, various points refined, discussion expanded, references updated, typos corrected, published in JHEP 1105:091,201

Magnetic Coupling in the Quiet Solar Atmosphere

Three kinds of magnetic couplings in the quiet solar atmosphere are highlighted and discussed, all fundamentally connected to the Lorentz force. First the coupling of the convecting and overshooting fluid in the surface layers of the Sun with the magnetic field. Here, the plasma motion provides the dominant force, which shapes the magnetic field and drives the surface dynamo. Progress in the understanding of the horizontal magnetic field is summarized and discussed. Second, the coupling between acoustic waves and the magnetic field, in particular the phenomenon of wave conversion and wave refraction. It is described how measurements of wave travel times in the atmosphere can provide information about the topography of the wave conversion zone, i.e., the surface of equal Alfv\'en and sound speed. In quiet regions, this surface separates a highly dynamic magnetic field with fast moving magnetosonic waves and shocks around and above it from the more slowly evolving field of high-beta plasma below it. Third, the magnetic field also couples to the radiation field, which leads to radiative flux channeling and increased anisotropy in the radiation field. It is shown how faculae can be understood in terms of this effect. The article starts with an introduction to the magnetic field of the quiet Sun in the light of new results from the Hinode space observatory and with a brief survey of measurements of the turbulent magnetic field with the help of the Hanle effect.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Invasion speeds for structured populations in fluctuating environments

We live in a time where climate models predict future increases in environmental variability and biological invasions are becoming increasingly frequent. A key to developing effective responses to biological invasions in increasingly variable environments will be estimates of their rates of spatial spread and the associated uncertainty of these estimates. Using stochastic, stage-structured, integro-difference equation models, we show analytically that invasion speeds are asymptotically normally distributed with a variance that decreases in time. We apply our methods to a simple juvenile-adult model with stochastic variation in reproduction and an illustrative example with published data for the perennial herb, \emph{Calathea ovandensis}. These examples buttressed by additional analysis reveal that increased variability in vital rates simultaneously slow down invasions yet generate greater uncertainty about rates of spatial spread. Moreover, while temporal autocorrelations in vital rates inflate variability in invasion speeds, the effect of these autocorrelations on the average invasion speed can be positive or negative depending on life history traits and how well vital rates ``remember'' the past

The Influence of Mirror-Visual Feedback on Training-Induced Motor Performance Gains in the Untrained Hand

The well-documented observation of bilateral performance gains following unilateral motor training, a phenomenon known as cross-limb transfer, has important implications for rehabilitation. It has recently been shown that provision of a mirror image of the active hand during unilateral motor training has the capacity to enhance the efficacy of this phenomenon when compared to training without augmented visual feedback (i.e., watching the passive hand), possibly via action observation effects [1]. The current experiment was designed to confirm whether mirror-visual feedback (MVF) during motor training can indeed elicit greater performance gains in the untrained hand compared to more standard visual feedback (i.e., watching the active hand). Furthermore, discussing the mechanisms underlying any such MVF-induced behavioural effects, we suggest that action observation and the cross-activation hypothesis may both play important roles in eliciting cross-limb transfer. Eighty participants practiced a fast-as-possible two-ball rotation task with their dominant hand. During training, three different groups were provided with concurrent visual feedback of the active hand, inactive hand or a mirror image of the active hand with a fourth control group receiving no training. Pre- and post-training performance was measured in both hands. MVF did not increase the extent of training-induced performance changes in the untrained hand following unilateral training above and beyond those observed for other types of feedback. The data are consistent with the notion that cross-limb transfer, when combined with MVF, is mediated by cross-activation with action observation playing a less unique role than previously suggested. Further research is needed to replicate the current and previous studies to determine the clinical relevance and potential benefits of MVF for cases that, due to the severity of impairment, rely on unilateral training programmes of the unaffected limb to drive changes in the contralateral affected limb

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics

Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency

Purpose: Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. Methods: We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. Results: There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. Conclusions: Our findings provide a direct link between disruption of the cone mosaic and L/M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus

Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer

In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa

POSIWID and determinism in design for behaviour change

Copyright @ 2012 Social Services Research GroupWhen designing to influence behaviour for social or environmental benefit, does designers' intent matter? Or are the effects on behaviour more important, regardless of the intent involved? This brief paper explores -- in the context of design for behaviour change -- some treatments of design, intentionality, purpose and responsibility from a variety of fields, including Stafford Beer's "The purpose of a system is what it does" and Maurice Broady's perspective on determinism. The paper attempts to extract useful implications for designers working on behaviour-related problems, in terms of analytical or reflective questions to ask during the design process