Natural variation in immune responses to neonatal mycobacterium bovis bacillus calmette-guerin (BCG) vaccination in a cohort of Gambian infants

Background There is a need for new vaccines for tuberculosis (TB) that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-) is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN- responses to BCG in this age group are poorly described. Characterisation of IFN- responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. Methodology/Principal Findings 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-, interleukin (IL)-5 and IL-13 responses to purified protein derivative (PPD), killed Mycobacterium tuberculosis (KMTB), M. tuberculosis short term culture filtrate (STCF) and M. bovis BCG antigen 85 complex (Ag85) were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen) made IFN- responses and there was significant correlation between IFN- responses to the different mycobacterial antigens (Spearman’s coefficient ranged from 0.340 to 0.675, p=10-6-10-22). IL-13 and IL-5 responses were generally low and there were more non-responders (33-75%) for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens Conclusions/Significance Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine variation in IFN- responses

Strong Double Higgs Production at the LHC

The hierarchy problem and the electroweak data, together, provide a plausible motivation for considering a light Higgs emerging as a pseudo-Goldstone boson from a strongly-coupled sector. In that scenario, the rates for Higgs production and decay differ significantly from those in the Standard Model. However, one genuine strong coupling signature is the growth with energy of the scattering amplitudes among the Goldstone bosons, the longitudinally polarized vector bosons as well as the Higgs boson itself. The rate for double Higgs production in vector boson fusion is thus enhanced with respect to its negligible rate in the SM. We study that reaction in pp collisions, where the production of two Higgs bosons at high pT is associated with the emission of two forward jets. We concentrate on the decay mode hh -> WW^(*)WW^(*) and study the semi-leptonic decay chains of the W's with 2, 3 or 4 leptons in the final states. While the 3 lepton final states are the most relevant and can lead to a 3 sigma signal significance with 300 fb^{-1} collected at a 14 TeV LHC, the two same-sign lepton final states provide complementary information. We also comment on the prospects for improving the detectability of double Higgs production at the foreseen LHC energy and luminosity upgrades.Comment: 54 pages, 26 figures. v2: typos corrected, a few comments and one table added. Version published in JHE

Upper atmospheres and ionospheres of planets and satellites

The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

Relation between sleep quality and quantity, quality of life, and risk of developing diabetes in healthy workers in Japan: the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study

<p>Abstract</p> <p>Background</p> <p>The effect of sleep on the risk of developing diabetes has not been explored in an Asian population. The objective of this study is to investigate the effect of self-reported sleep duration and sleep quality on the risk of developing diabetes in a prospective cohort in Japan.</p> <p>Methods</p> <p>Data were analyzed from the cohort of participants in a High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP), conducted in Japan from the year 1999 until 2004. A Cox proportional hazard model was used to evaluate the association between sleep duration or sleep quality and the risk of diabetes.</p> <p>Results</p> <p>Of 6509 participants (26.1% of women, 19–69 years of age), a total of 230 type 2 diabetes cases were reported over a median 4.2 years of follow-up. For participants who often experienced difficulty in initiating sleep, the multivariate-adjusted hazard ratios for diabetes were 1.42 (95%CI, 1.05–1.91) in participants with a medium frequency of difficulty initiating sleep, and 1.61 (95%CI, 1.00–2.58) for those with a high frequency, with a statistically significant linear trend. Significant association was not observed in the association between difficulty of maintaining sleep or duration of sleep, and risk of diabetes.</p> <p>Conclusion</p> <p>Medium and high frequencies of difficulty initiating sleep, but not difficulty in maintaining sleep or in sleep duration, are associated with higher risks of diabetes in relatively healthy Asian workers, even after adjusting for a large number of possible further factors.</p

Cough and its importance in COPD

Patients with COPD most frequently complain of breathlessness and cough and these are both increased during exacerbations. Studies have generally focused on quality of life during end-stage disease, where breathlessness becomes dominant and cough less important. There are very little data on the frequency and severity of cough in COPD or its impact on quality of life at different stages of disease. Little is known about the factors that influence objective cough counts in COPD. Cough may be a marker for progressive disease in milder COPD patients who continue to smoke, and it may be useful in case-finding for milder disease in the community. The cough reflex sensitivity is heightened in COPD compared with healthy volunteers and similar to that in subjects with asthma. The degree of airflow obstruction does not predict cough reflex sensitivity or objective cough counts, implying an independent process. Effective treatments for cough in COPD have not yet been identified. Improved outcome measures of cough, a better understanding of cough in the natural history of COPD, and its importance to patients are needed

Explaining the de-prioritization of primary prevention: Physicians' perceptions of their role in the delivery of primary care

BACKGROUND: While physicians are key to primary preventive care, their delivery rate is sub-optimal. Assessment of physician beliefs is integral to understanding current behavior and the conceptualization of strategies to increase delivery. METHODS: A focus group with regional primary care physician (PCP) Opinion Leaders was conducted as a formative step towards regional assessment of attitudes and barriers regarding preventive care delivery in primary care. Following the PRECEDE-PROCEED model, the focus group aim was to identify conceptual themes that characterize PCP beliefs and practices regarding preventive care. Seven male and five female PCPs (family medicine, internal medicine) participated in the audiotaped discussion of their perceptions and behaviors in delivery of primary preventive care. The transcribed audiotape was qualitatively analyzed using grounded theory methodology. RESULTS: The PCPs' own perceived role in daily practice was a significant barrier to primary preventive care. The prevailing PCP model was the "one-stop-shop" physician who could provide anything from primary to tertiary care, but whose provision was dominated by the delivery of immediate diagnoses and treatments, namely secondary care. CONCLUSIONS: The secondary-tertiary prevention PCP model sustained the expectation of immediacy of corrective action, cure, and satisfaction sought by patients and physicians alike, and, thereby, de-prioritized primary prevention in practice. Multiple barriers beyond the immediate control of PCP must be surmounted for the full integration of primary prevention in primary care practice. However, independent of other barriers, physician cognitive value of primary prevention in practice, a base mediator of physician behavior, will need to be increased to frame the likelihood of such integration

Does Social Capital Promote Physical Activity? A Population-Based Study in Japan

To examine the association between individual-level social capital and physical activity.In February 2009, data were collected in a population-based cross-sectional survey in Okayama city, Japan. A cluster-sampling approach was used to randomly select 4,000 residents from 20 school districts. A total of 2260 questionnaires were returned (response rate: 57.4%). Individual-level social capital was assessed by an item inquiring about perceived trust of others in the community (cognitive dimension of social capital) categorized as low trust (43.0%), mid trust (38.6%), and high trust (17.3%), as well as participation in voluntary groups (structural dimension of social capital), which further distinguished between bonding (8.9%) and bridging (27.1%) social capital. Using logistic regression, we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for physical inactivity associated with each domain of social capital. Multiple imputation method was employed for missing data. Among total participants, 68.8% were physically active and 28.9% were inactive. Higher trust was associated with a significantly lower odds of physical inactivity (OR = 0.58, 95% CI = 0.42-0.79) compared with low trust. Both bridging and bonding social capital were marginally significantly associated with lower odds of physical inactivity (bridging, OR = 0.79, 95% CI = 0.62-1.00; bonding, OR = 0.71, 95% CI = 0.48-1.03) compared with lack of structural social capital.Low individual-level social capital, especially lower trust of others in the community, was associated with physical inactivity among Japanese adults

The six-minute walk test in community dwelling elderly: influence of health status.

BACKGROUND: The 6 minutes walk test (6MWT) is a useful assessment instrument for the exercise capacity of elderly persons. The impact of the health status on the 6MWT-distance in elderly, however, remains unclear, reducing its value in clinical settings. The objective of this study was to investigate to what extent the 6MWT-distance in community dwelling elderly is determined by health conditions. METHODS: One hundred and fifty-six community dwelling elderly people (53 male, 103 female) were assessed for health status and performed the 6MWT. After clinical evaluation, electrocardiography and laboratory examination participants were categorized into a stratified six-level classification system according to their health status, going from A (completely healthy) to D (signs of active disease at the moment of examination). RESULTS: The mean 6MWT-distance was 603 m (SD = 178). The 6MWT-distance decreased significantly with increasing age (ANOVA p = 0.0001) and with worsening health status (ANCOVA, corrected for age p < 0.001). A multiple linear regression model with health status, age and gender as independent variables explained 31% of the 6MWT-distance variability. Anthropometrical measures (stature, weight and BMI) did not significantly improve the prediction model. A significant relationship between 6MWT-distance and stature was only present in category A (completely healthy). CONCLUSIONS: Significant differences in 6MWT-distance are observed according to health status in community-dwelling elderly persons. The proposed health categorizing system for elderly people is able to distinguish persons with lower physical exercise capacity and can be useful when advising physical trainers for seniors

Associations between school-based peer networks and smoking according to socioeconomic status and tobacco control context:protocol for a mixed method systematic review

Background Smoking remains a major public health concern. School-based social networks influence uptake of smoking among peers. During the past two decades, the UK macro-systemic context within which schools are nested and interact with has changed, with anti-smoking norms having become set at a more macro-systemic level. Whilst the overall prevalence of smoking in the UK has decreased, inequality has prevailed. It is plausible that the influence of school-based social networks on smoking uptake may vary according to socioeconomic status. Therefore, this study aims to understand how social influence on smoking among adolescents has changed in line with variance within and between contexts according to time and geography. Methods The following databases will be searched: Medline, PsycINFO, Embase, Applied Social Sciences Index and Abstracts (ASSIA), British Education Index, Sociological abstracts, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Education Resources Information Center (ERIC) and Scopus. Additional searches will include reference checking of key papers, citation tracking, word of mouth and grey literature searches. The search strategies will incorporate terms relating to smoking, adolescents, schools, peers, network analysis and qualitative research. Titles and abstracts and full texts will be independently screened and assessed for quality by at least two researchers. Included studies will be assessed for quality, and data will be extracted for synthesis, including participant characteristics, setting and tobacco control context, study design and methods, analysis and results and conclusions. Quantitative findings will be narratively synthesised, whilst a lines of argument synthesis combined with refutational analysis will be employed to synthesise qualitative data. Both sets of findings will be charted on a timeline to add context to network findings and obtain an enhanced understanding of changes over time. Discussion This protocol is for a mixed methods synthesis of both social network findings, to investigate social structures and qualitative studies, to elicit contextual information. The review will synthesise changes in the context of social influence on adolescent smoking over time and geographically. As context is increasingly recognised as a key source of complexity, this enhanced understanding will help to inform future interventions targeting smoking through social influence. This will help to enhance their relevance to context, subsequent effectiveness and targeting of inequalities