The Geographic Synchrony of Seasonal Influenza: A Waves across Canada and the United States

BACKGROUND: As observed during the 2009 pandemic, a novel influenza virus can spread globally before the epidemic peaks locally. As consistencies in the relative timing and direction of spread could form the basis for an early alert system, the objectives of this study were to use the case-based reporting system for laboratory confirmed influenza from the Canadian FluWatch surveillance program to identify the geographic scale at which spatial synchrony exists and then to describe the geographic patterns of influenza A virus across Canada and in relationship to activity in the United States (US). METHODOLOGY/PRINCIPAL FINDINGS: Weekly laboratory confirmations for influenza A were obtained from the Canadian FluWatch and the US FluView surveillance programs from 1997/98 to 2006/07. For the six seasons where at least 80% of the specimens were antigenically similar, we identified the epidemic midpoint of the local/regional/provincial epidemics and analyzed trends in the direction of spread. In three out of the six seasons, the epidemic appeared first in Canada. Regional epidemics were more closely synchronized across the US (3-5 weeks) compared to Canada (5-13 weeks), with a slight gradient in timing from the southwest regions in the US to northeast regions of Canada and the US. Cities, as well as rural areas within provinces, usually peaked within a couple of weeks of each other. The anticipated delay in peak activity between large cities and rural areas was not observed. In some mixed influenza A seasons, lack of synchronization sub-provincially was evident. CONCLUSIONS/SIGNIFICANCE: As mixing between regions appears to be too weak to force a consistency in the direction and timing of spread, local laboratory-based surveillance is needed to accurately assess the level of influenza activity in the community. In comparison, mixing between urban communities and adjacent rural areas, and between some communities, may be sufficient to force synchronization

The age-metallicity structure of the Milky Way disc using APOGEE

The measurement of the structure of stellar populations in the Milky Way disc places fundamental constraints on models of galaxy formation and evolution. Previously, the disc’s structure has been studied in terms of populations defined geometrically and/or chemically, but a decomposition based on stellar ages provides a more direct connection to the history of the disc, and stronger constraint on theory. Here, we use positions, abundances and ages for 31 244 red giant branch stars from the Sloan Digital Sky Survey (SDSS)-APOGEE survey, spanning 3 < Rgc < 15 kpc, to dissect the disc into mono-age and mono-[Fe/H] populations at low and high [α/Fe]. For each population, with age < 2 Gyr and [Fe/H] < 0.1 dex, we measure the structure and surface-mass density contribution. We find that low [α/Fe] mono-age populations are fit well by a broken exponential, which increases to a peak radius and decreases thereafter. We show that this profile becomes broader with age, interpreted here as a new signal of disc heating and radial migration. High [α/Fe] populations are well fit as single exponentials within the radial range considered, with an average scalelength of 1.9 ± 0.1 kpc. We find that the relative contribution of high to low [α/Fe] populations at R0 is f� = 18 per cent ± 5 per cent; high [α/Fe] contributes most of the mass at old ages, and low [α/Fe] at young ages. The low and high [α/Fe] populations overlap in age at intermediate [Fe/H], although both contribute mass at R0 across the full range of [Fe/H]. The mass-weighted scaleheight hZ distribution is a smoothly declining exponential function. High [α/Fe] populations are thicker than low [α/Fe], and the average hZ increases steadily with age, between 200 and 600 pc

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research

Big hearts, small hands:A focus group study exploring parental food portion behaviours

© The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: The development of healthy food portion sizes among families is deemed critical to childhood weight management; yet little is known about the interacting factors influencing parents' portion control behaviours. This study aimed to use two synergistic theoretical models of behaviour: the COM-B model (Capability, Opportunity, Motivation - Behaviour) and Theoretical Domains Framework (TDF) to identify a broad spectrum of theoretically derived influences on parents' portion control behaviours including examination of affective and habitual influences often excluded from prevailing theories of behaviour change. Methods: Six focus groups exploring family weight management comprised of one with caseworkers (n = 4), four with parents of overweight children (n = 14) and one with parents of healthy weight children (n = 8). A thematic analysis was performed across the dataset where the TDF/COM-B were used as coding frameworks. Results: To achieve the target behaviour, the behavioural analysis revealed the need for eliciting change in all three COM-B domains and nine associated TDF domains. Findings suggest parents' internal processes such as their emotional responses, habits and beliefs, along with social influences from partners and grandparents, and environmental influences relating to items such as household objects, interact to influence portion size behaviours within the home environment. Conclusion: This is the first study underpinned by COM-B/TDF frameworks applied to childhood weight management and provides new targets for intervention development and the opportunity for future research to explore the mediating and moderating effects of these variables on one another.Peer reviewedFinal Published versio

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Comparison of multiplex meta analysis techniques for understanding the acute rejection of solid organ transplants

<p>Abstract</p> <p>Background</p> <p>Combining the results of studies using highly parallelized measurements of gene expression such as microarrays and RNAseq offer unique challenges in meta analysis. Motivated by a need for a deeper understanding of organ transplant rejection, we combine the data from five separate studies to compare acute rejection versus stability after solid organ transplantation, and use this data to examine approaches to multiplex meta analysis.</p> <p>Results</p> <p>We demonstrate that a commonly used parametric effect size estimate approach and a commonly used non-parametric method give very different results in prioritizing genes. The parametric method providing a meta effect estimate was superior at ranking genes based on our gold-standard of identifying immune response genes in the transplant rejection datasets.</p> <p>Conclusion</p> <p>Different methods of multiplex analysis can give substantially different results. The method which is best for any given application will likely depend on the particular domain, and it remains for future work to see if any one method is consistently better at identifying important biological signal across gene expression experiments.</p

Integrative care for the management of low back pain: use of a clinical care pathway

<p>Abstract</p> <p>Background</p> <p>For the treatment of chronic back pain, it has been theorized that integrative care plans can lead to better outcomes than those achieved by monodisciplinary care alone, especially when using a collaborative, interdisciplinary, and non-hierarchical team approach. This paper describes the use of a care pathway designed to guide treatment by an integrative group of providers within a randomized controlled trial.</p> <p>Methods</p> <p>A clinical care pathway was used by a multidisciplinary group of providers, which included acupuncturists, chiropractors, cognitive behavioral therapists, exercise therapists, massage therapists and primary care physicians. Treatment recommendations were based on an evidence-informed practice model, and reached by group consensus. Research study participants were empowered to select one of the treatment recommendations proposed by the integrative group. Common principles and benchmarks were established to guide treatment management throughout the study.</p> <p>Results</p> <p>Thirteen providers representing 5 healthcare professions collaborated to provide integrative care to study participants. On average, 3 to 4 treatment plans, each consisting of 2 to 3 modalities, were recommended to study participants. Exercise, massage, and acupuncture were both most commonly recommended by the team and selected by study participants. Changes to care commonly incorporated cognitive behavioral therapy into treatment plans.</p> <p>Conclusion</p> <p>This clinical care pathway was a useful tool for the consistent application of evidence-based care for low back pain in the context of an integrative setting.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00567333</p

Evaluation of the in vitro skin permeation of antiviral drugs from penciclovir 1% cream and acyclovir 5% cream used to treat herpes simplex virus infection

<p>Abstract</p> <p>Background</p> <p>Herpes simplex virus infection (HSV) is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis) or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the <it>in vitro </it>skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores), using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm²of acyclovir 5% cream or penciclovir 1% cream.</p> <p>Methods</p> <p>After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physico-chemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips.</p> <p>Results</p> <p>Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells.</p> <p>Conclusion</p> <p>Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of penciclovir through the epidermis into the deeper basal cells.</p

Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior

Control strategies enforced by health agencies are a major type of practice to contain influenza outbreaks. Another type of practice is the voluntary preventive behavior of individuals, such as receiving vaccination, taking antiviral drugs, and wearing face masks. These two types of practices take effects concurrently in influenza containment, but little attention has been paid to their combined effectiveness. This article estimates this combined effectiveness using established simulation models in the urbanized area of Buffalo, NY, USA. Three control strategies are investigated, including: Targeted Antiviral Prophylaxis (TAP), workplace/school closure, community travel restriction, as well as the combination of the three. All control strategies are simulated with and without regard to individual preventive behavior, and the resulting effectiveness are compared. The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. The preventive behavior of individuals could save medical resources for control strategies and avoid unnecessary socio-economic interruptions. This research adds a human behavioral dimension into the simulation of control strategies and offers new insights into disease containment. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment