Electroweak Baryogenesis and Dark Matter with an approximate R-symmetry

It is well known that R-symmetric models dramatically alleviate the SUSY flavor and CP problems. We study particular modifications of existing R-symmetric models which share the solution to the above problems, and have interesting consequences for electroweak baryogenesis and the Dark Matter (DM) content of the universe. In particular, we find that it is naturally possible to have a strongly first-order electroweak phase transition while simultaneously relaxing the tension with EDM experiments. The R-symmetry (and its small breaking) implies that the gauginos (and the neutralino LSP) are pseudo-Dirac fermions, which is relevant for both baryogenesis and DM. The singlet superpartner of the U(1)_Y pseudo-Dirac gaugino plays a prominent role in making the electroweak phase transition strongly first-order. The pseudo-Dirac nature of the LSP allows it to behave similarly to a Dirac particle during freeze-out, but like a Majorana particle for annihilation today and in scattering against nuclei, thus being consistent with current constraints. Assuming a standard cosmology, it is possible to simultaneously have a strongly first-order phase transition conducive to baryogenesis and have the LSP provide the full DM relic abundance, in part of the allowed parameter space. However, other possibilities for DM also exist, which are discussed. It is expected that upcoming direct DM searches as well as neutrino signals from DM annihilation in the Sun will be sensitive to this class of models. Interesting collider and Gravity-wave signals are also briefly discussed.Comment: 50 pages, 10 figure

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Intensive group training protocol versus guideline physiotherapy for patients with chronic low back pain: a randomised controlled trial

Intensive group training using principles of graded activity has been proven to be effective in occupational care for workers with chronic low back pain. Objective of the study was to compare the effects of an intensive group training protocol aimed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain. The study was designed as pragmatic randomised controlled trial with a setup of 105 primary care physiotherapists in 49 practices and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study. In the intensive group training protocol exercise therapy, back school and operant-conditioning behavioural principles are combined. Patients were treated during 10 individual sessions along 20 group sessions. Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain. Main outcome measures were functional disability (Roland Morris disability questionnaire), pain intensity, perceived recovery and sick leave because of low back pain assessed at baseline and after 6, 13, 26 and 52 weeks. Both an intention-to-treat analysis and a per-protocol analysis were performed. Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period, with one exception. After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group, but this difference was absent after 52 weeks. We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain

Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials

BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802

Phylogeography of Recently Emerged DENV-2 in Southern Viet Nam

Revealing the dispersal of dengue viruses (DENV) in time and space is central to understanding their epidemiology. However, the processes that shape DENV transmission patterns at the scale of local populations are not well understood, particularly the impact of such factors as human population movement and urbanization. Herein, we investigated trends in the spatial dynamics of DENV-2 transmission in the highly endemic setting of southern Viet Nam. Through a phylogeographic analysis of 168 full-length DENV-2 genome sequences obtained from hospitalized dengue cases from 10 provinces in southern Viet Nam, we reveal substantial genetic diversity in both urban and rural areas, with multiple lineages identified in individual provinces within a single season, and indicative of frequent viral migration among communities. Focusing on the recently introduced Asian I genotype, we observed particularly high rates of viral exchange between adjacent geographic areas, and between Ho Chi Minh City, the primary urban center of this region, and populations across southern Viet Nam. Within Ho Chi Minh City, patterns of DENV movement appear consistent with a gravity model of virus dispersal, with viruses traveling across a gradient of population density. Overall, our analysis suggests that Ho Chi Minh City may act as a source population for the dispersal of DENV across southern Viet Nam, and provides further evidence that urban areas of Southeast Asia play a primary role in DENV transmission. However, these data also indicate that more rural areas are also capable of maintaining virus populations and hence fueling DENV evolution over multiple seasons

The long-term effects of naprapathic manual therapy on back and neck pain - Results from a pragmatic randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Back and neck pain are very common, disabling and recurrent disorders in the general population and the knowledge of long-term effect of treatments are sparse. The aim of this study was to compare the long-term effects (up to one year) of naprapathic manual therapy and evidence-based advice on staying active regarding non-specific back and/or neck pain. Naprapathy, a health profession mainly practiced in Sweden, Finland, Norway and in the USA, is characterized by a combination of manual musculoskeletal manipulations, aiming to decrease pain and disability in the neuromusculoskeletal system.</p> <p>Methods</p> <p>Subjects with non-specific pain/disability in the back and/or neck lasting for at least two weeks (n = 409), recruited at public companies in Sweden, were included in this pragmatic randomized controlled trial. The two interventions compared were naprapathic manual therapy such as spinal manipulation/mobilization, massage and stretching, (<it>Index Group</it>), and advice to stay active and on how to cope with pain, provided by a physician (C<it>ontrol Group</it>). Pain intensity, disability and health status were measured by questionnaires.</p> <p>Results</p> <p>89% completed the 26-week follow-up and 85% the 52-week follow-up. A higher proportion in the Index Group had a clinically important decrease in pain (risk difference (RD) = 21%, <it>95% CI: 10-30</it>) and disability (RD = 11%, <it>95% CI: 4-22</it>) at 26-week, as well as at 52-week follow-ups (pain: RD = 17%, <it>95% CI: 7-27 </it>and disability: RD = 17%, <it>95% CI: 5-28</it>). The differences between the groups in pain and disability considered over one year were statistically significant favoring naprapathy (p ≤ 0.005). There were also significant differences in improvement in bodily pain and social function (subscales of SF-36 health status) favoring the Index Group.</p> <p>Conclusions</p> <p>Combined manual therapy, like naprapathy, is effective in the short and in the long term, and might be considered for patients with non-specific back and/or neck pain.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN56954776.</p

The HAPPY (Healthy and Active Parenting Programmme for early Years) feasibility randomised control trial: acceptability and feasibility of an intervention to reduce infant obesity.

The prevalence of infant obesity is increasing, but there is a lack of evidence-based approaches to prevent obesity at this age. This study tested the acceptability and feasibility of evaluating a theory-based intervention aimed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy: the Healthy and Active Parenting Programme for Early Years (HAPPY).A feasibility randomised controlled trial was conducted in Bradford, England. One hundred twenty overweight/obese pregnant women (Body Mass Index [BMI] ≥25 kg/m(2)) were recruited between 10-26 weeks gestation. Consenting women were randomly allocated to HAPPY (6 antenatal, 6 postnatal sessions: N = 59) or usual care (N = 61). Appropriate outcome measures for a full trial were explored, including: infant's length and weight, woman's BMI, physical activity and dietary intake of the women and infants. Health economic data were collected. Measurement occurred before randomisation and when the infant was aged 6 months and 12 months. Feasibility outcomes were: recruitment/attrition rates, and acceptability of: randomisation, measurement, and intervention. Intra-class correlations for infant weight were calculated. Fidelity was assessed through observations and facilitator feedback. Focus groups and semi-structured interviews explored acceptability of methods, implementation, and intervention content.Recruitment targets were met (~20 women/month) with a recruitment rate of 30 % of eligible women (120/396). There was 30 % attrition at 12 months; 66 % of recruited women failed to attend intervention sessions, but those who attended the first session were likely to continue to attend (mean 9.4/12 sessions, range 1-12). Reaction to intervention content was positive, and fidelity was high. Group clustering was minimal; an adjusted effect size of -0.25 standard deviation scores for infant weight at 12 months (95 % CI: -0.16-0.65) favouring the intervention was observed using intention to treat analyses. No adverse events were reported.The HAPPY intervention appeared feasible and acceptable to participants who attended and those delivering it, however attendance was low; adaptations to increase initial attendance are recommended. Whilst the study was not powered to detect a definitive effect, our results suggest a potential to reduce risk of infant obesity. The evidence reported provides valuable lessons to inform progression to a definitive trial.Current Controlled Trials ISRCTN56735429

Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor

T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells