Workplace exposure to passive smoking and risk of cardiovascular disease: summary of epidemiologic studies.

We reviewed the published epidemiologic studies addressing the relationship between workplace exposure to environmental tobacco smoke (ETS) and cardiovascular disease risk in three case-control studies and three cohort studies. Although the point estimates of risk for cardiovascular disease exceeded 1.0 in five of six studies, none of the relative risks was statistically significant because of the small number of cardiovascular end points occurring in individual studies. In common with most epidemiologic investigations of the health risks of ETS, none of the workplace studies included independent biochemical validation of ETS exposure. In contrast to the evidence on increased cardiovascular disease risk from exposure to spousal ETS, studies of ETS exposure in the workplace are still sparse and inconclusive. Conversely, there is no biologically plausible reason to believe that the hazards of ETS exposure that have been demonstrated in the home should not also apply to the workplace

Pregnancy and helminth infections.

It has been proposed that helminth infection may be particularly detrimental during pregnancy, through adverse effects on maternal anaemia and on birth outcomes, and that anthelminthic treatment during pregnancy will therefore be particularly beneficial. However, the few treatment trials that have been conducted have given, but little support to this notion and further trials in settings of nutritional stress are needed. It has also been proposed that prenatal exposure to helminth infection has an important effect on the development of the foetal immune response. There is evidence that this may impact, long-term, upon responses to helminth and nonhelminth antigens, and to allergens. Exposure to helminths in utero may also have nonspecific effects that may modify the offspring's susceptibility to diseases mediated by inflammation, including metabolic disorders. The mechanisms of such effects are not known, but they deserve to be explored as current epidemiological findings suggest the possibility of primary prevention for inflammatory conditions such as allergy, through intervention during pregnancy

A prototype tool to enable farmers to measure and improve the welfare performance of the farm animal enterprise: The unified field index

Schemes for the assessment of farm animal welfare and assurance of welfare standards have proliferated in recent years. An acknowledged short-coming has been the lack of impact of these schemes on the welfare standards achieved on farm due in part to sociological factors concerning their implementation. Here we propose the concept of elfare performance based on a broad set of performance attributes of an enterprise and describe a tool based on risk assessment and benchmarking methods for measuring and managing welfare performance. The tool termed the Unified Field Index is presented in a general form comprising three modules addressing animal, resource, and management factors. Domains within these modules accommodate the principle conceptual perspectives for welfare assessment: biological functioning; emotional states; and naturalness. Pan-enterprise analysis in any livestock sector could be used to benchmark welfare performance of individual enterprises and also provide statistics of welfare performance for the livestock sector. An advantage of this concept of welfare performance is its use of continuous scales of measurement rather than traditional pass/fail measures. Through the feedback provided via benchmarking, the tool should help farmers better engage in on-going improvement of farm practices that affect animal welfare

Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: Different boosting intervals and implications for efficacy trials

Objectives. To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen 85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. Design. There are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG. These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naı¨ve adults. Subjects were vaccinated with BCG alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime–MVA85A boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination was administered many years after vaccination with BCG. Results. MVA85A was safe and highly immunogenic when administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were compared with the previous long interval trial data, there were no significant differences in the magnitude of immune responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. Conclusions. The clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses. This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data presented here. Trial Registration. ClinicalTrials.Oxford University was the sponsor for all the clinical trials reported here

Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development

Predicting live birth, preterm and low birth weight infant after in-vitro fertilisation: a prospective study of 144018 treatment cycles

Background The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. Methods and Findings We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia. Conclusions Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF

Impact of metabolic comorbidity on the association between body mass index and heatlh-related quality of life: a Scotland-wide cross-sectional study of 5,608 participants

<p/>Background: The prevalence of obesity is rising in Scotland and globally. Overall, obesity is associated with increased morbidity, mortality and reduced health-related quality of life. Studies suggest that "healthy obesity" (obesity without metabolic comorbidity) may not be associated with morbidity or mortality. Its impact on health-related quality of life is unknown. <p/>Methods: We extracted data from the Scottish Health Survey on self-reported health-related quality of life, body mass index (BMI), demographic information and comorbidity. SF-12 responses were converted into an overall health utility score. Linear regression analyses were used to explore the association between BMI and health utility, stratified by the presence or absence of metabolic comorbidity (diabetes, hypertension, hypercholesterolemia or cardiovascular disease), and adjusted for potential confounders (age, sex and deprivation quintile). <p/>Results: Of the 5,608 individuals, 3,744 (66.8%) were either overweight or obese and 921 (16.4%) had metabolic comorbidity. There was an inverted U-shaped relationship whereby health utility was highest among overweight individuals and fell with increasing BMI. There was a significant interaction with metabolic comorbidity (p = 0.007). Individuals with metabolic comorbidty had lower utility scores and a steeper decline in utility with increasing BMI (morbidly obese, adjusted coefficient: -0.064, 95% CI -0.115, -0.012, p = 0.015 for metabolic comorbidity versus -0.042, 95% CI -0.067, -0.018, p = 0.001 for no metabolic comorbidity). <p/>Conclusions: The adverse impact of obesity on health-related quality of life is greater among individuals with metabolic comorbidity. However, increased BMI is associated with reduced health-related quality of life even in the absence of metabolic comorbidity, casting doubt on the notion of "healthy obesity"

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

The progesterone receptor Val660→Leu polymorphism and breast cancer risk

BACKGROUND: Recent evidence suggests a role for progesterone in breast cancer development and tumorigenesis. Progesterone exerts its effect on target cells by interacting with its receptor; thus, genetic variations, which might cause alterations in the biological function in the progesterone receptor (PGR), can potentially contribute to an individual's susceptibility to breast cancer. It has been reported that the PROGINS allele, which is in complete linkage disequilibrium with a missense substitution in exon 4 (G/T, valine→leucine, at codon 660), is associated with a decreased risk for breast cancer. METHODS: Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 1252 cases and 1660 matched controls with the use of the Taqman assay. RESULTS: We did not observe any association of breast cancer risk with carrying the G/T (Val660→Leu) polymorphism (odds ratio 1.10, 95% confidence interval 0.93–1.30). In addition, we did not observe an interaction between this allele and menopausal status and family history of breast cancer as reported previously. CONCLUSION: Overall, our study does not support an association between the Val660→Leu PROGINS polymorphism and breast cancer risk