Assessment and validation of exposure to disinfection by-products during pregnancy, in an epidemiological study examining associated risk of adverse fetal growth outcomes

Studies investigating exposure to disinfection by-products (DBPs) via chlorinated waters during pregnancy and adverse fetal growth outcomes have been limited by potential exposure measurement error, lack of exposure assessment validation and potential residual confounding. Factors driving DBP exposure are poorly understood, making it difficult to target resources appropriately in order to improve exposure assessment. These issues were investigated through DBP exposure assessment and validation for a new investigation of DBPs and fetal growth within the Born in Bradford (BiB) cohort study. Analysis of individual water use in the BiB cohort found that water consumption, showering, bathing and swimming varied by demographic and lifestyle factors. Sampling, analysis, and modelling of trihalomethanes (THMs) in tap water showed that THM concentrations exhibited clear seasonal variation, but spatial variability was limited across the study area. Various metrics of exposure to THMs during pregnancy were created, including ‘personalised’ semi-individual metrics. Analysis of these metrics revealed individual water use to be the main driver of THM exposure in this cohort, with spatial and temporal variability having little influence. Compared with a fully integrated THM exposure metric (incorporating ingestion, showering/bathing and swimming), metrics based only on THM concentrations or THM ingestion misclassified over 50% of women. A nested validation study was conducted using a 7-day water diary and urinary trichloroacetic acid (TCAA) biomarker. This found error in self-reported water use and TCAA ingestion estimates to vary by employment status - error being greater for employed women. Urinary TCAA was not correlated with TCAA in tap water, reinforcing that individual water use is the most influential driver of DBP exposure in this cohort. Recommendations for future research include improved individual water use assessment covering more activities and time-points in pregnancy, stratified analysis of questionnaire validation studies, and use of urinary TCAA as a main exposure measure in epidemiological studies

Assessment and validation of exposure to disinfection by-products during pregnancy, in an epidemiological study examining associated risk of adverse fetal growth outcomes

Studies investigating exposure to disinfection by-products (DBPs) via chlorinated waters during pregnancy and adverse fetal growth outcomes have been limited by potential exposure measurement error, lack of exposure assessment validation and potential residual confounding. Factors driving DBP exposure are poorly understood, making it difficult to target resources appropriately in order to improve exposure assessment. These issues were investigated through DBP exposure assessment and validation for a new investigation of DBPs and fetal growth within the Born in Bradford (BiB) cohort study. Analysis of individual water use in the BiB cohort found that water consumption, showering, bathing and swimming varied by demographic and lifestyle factors. Sampling, analysis, and modelling of trihalomethanes (THMs) in tap water showed that THM concentrations exhibited clear seasonal variation, but spatial variability was limited across the study area. Various metrics of exposure to THMs during pregnancy were created, including ‘personalised’ semi-individual metrics. Analysis of these metrics revealed individual water use to be the main driver of THM exposure in this cohort, with spatial and temporal variability having little influence. Compared with a fully integrated THM exposure metric (incorporating ingestion, showering/bathing and swimming), metrics based only on THM concentrations or THM ingestion misclassified over 50% of women. A nested validation study was conducted using a 7-day water diary and urinary trichloroacetic acid (TCAA) biomarker. This found error in self-reported water use and TCAA ingestion estimates to vary by employment status - error being greater for employed women. Urinary TCAA was not correlated with TCAA in tap water, reinforcing that individual water use is the most influential driver of DBP exposure in this cohort. Recommendations for future research include improved individual water use assessment covering more activities and time-points in pregnancy, stratified analysis of questionnaire validation studies, and use of urinary TCAA as a main exposure measure in epidemiological studies

Progress in treatment of ANCA-associated vasculitis.

Autoantibodies to neutrophil cytoplasmic antigen-associated vasculitis (AAV) is characterised by inflammation of blood vessels. The introduction of immunosuppressive therapy with glucocorticoids and cyclophosphamide transformed AAV from a fatal condition to a largely treatable condition. Over the past 30 years, considerable progress has been made refining immunosuppressive regimens with a focus on minimising toxicity. There is, however, a high unmet need in the treatment of AAV. A proportion of patients are refractory to current therapies; 50% experience a relapse within 5 years and treatment toxicity contributes to mortality and chronic disability. As knowledge of the pathogenesis of vasculitis grows, it is mirrored by the availability of biological agents, which herald a revolution in the treatment of vasculitis. Lymphocyte-targeted and cytokine-targeted agents have been evaluated for the treatment of AAV and are entering the routine therapeutic arena with the potential to improve patient outcomes. As rare diseases, treatment advances in vasculitis depend on international collaborative research networks both to establish an evidence base for newer agents and to develop recommendations for patient management

Tap water use amongst pregnant women in a multi-ethnic cohort

<p>Abstract</p> <p>Background</p> <p>Studies of disinfection by-products in drinking water and measures of adverse fetal growth have often been limited by exposure assessment lacking data on individual water use, and therefore failing to reflect individual variation in DBP exposure.</p> <p>Methods</p> <p>Pregnant women recruited to the Born in Bradford cohort study completed a questionnaire which covers water exposure. Information was collected on water consumption, showering, bathing and swimming. Water exposure data from a subset of 39 women of the cohort are described here.</p> <p>Results</p> <p>Mean total tap water intake was 1.8 l/day, and women on average spent 146 minutes per week showering and bathing. Most tap water intake occurred at home (100% for unemployed, 71.8% for employed). Differences between age groups were observed for total tap water intake overall (p = 0.02) and at home (p = 0.01), and for bottled water intake (p = 0.05). There were differences between ethnic groups for tap water intake at home (p = 0.02) and total tap water intake at work (p = 0.02). Total tap water intake at work differed by income category (p = 0.001). Duration per shower was inversely correlated with age (Spearman's correlation -0.39, p = 0.02), and differed according to employment status (p = 0.04), ethnicity (p = 0.02) and income (p = 0.02).</p> <p>Conclusion</p> <p>This study provides estimates of water exposure in pregnant women in a multi-ethnic population in the north of England and suggests differences related to age, employment, income and ethnicity. The findings are valuable to inform exposure assessment in studies assessing the relationship between DBPs and adverse birth outcomes.</p

Ambient air pollution and adverse birth outcomes: A review of underlying mechanisms

Epidemiological data provide varying degrees of evidence for associations between prenatal exposure to ambient air pollutants and adverse birth outcomes (suboptimal measures of fetal growth, preterm birth and stillbirth). To assess further certainty of effects, this review examines the experimental literature base to identify mechanisms by which air pollution (particulate matter, nitrogen dioxide and ozone) could cause adverse effects on the developing fetus. It likely that this environmental insult impacts multiple biological pathways important for sustaining a healthy pregnancy, depending upon the composition of the pollutant mixture and the exposure window owing to changes in physiologic maturity of the placenta, its circulations and the fetus as pregnancy ensues. The current body of evidence indicates that the placenta is a target tissue, impacted by a variety of critical processes including nitrosative/oxidative stress, inflammation, endocrine disruption, epigenetic changes, as well as vascular dysregulation of the maternal‐fetal unit. All of the above can disturb placental function and, as a consequence, could contribute to compromised fetal growth as well increasing the risk of stillbirth. Furthermore, given that there is often an increased inflammatory response associated with preterm labour, inflammation is a plausible mechanism mediating the effects of air pollution on premature delivery. In the light of increased urbanisation and an ever‐changing climate, both of which increase ambient air pollution and negatively affect vulnerable populations such as pregnant individuals, it is hoped that the collective evidence may contribute to decisions taken to strengthen air quality policies, reductions in exposure to air pollution and subsequent improvements in the health of those not yet born

Randomized trial of enteric-coated mycophenolate sodium versus mycophenolate mofetil in multi-system autoimmune disease.

BACKGROUND: The use of mycophenolate mofetil (MMF) in autoimmune disease is often limited by adverse effects. In this single-centre, open label, parallel design study, we investigated whether enteric-coated mycophenolate sodium (MS) is better tolerated and therefore more efficacious than MMF in primary systemic vasculitis (PSV) and systemic lupus erythematosus (SLE). METHODS: Forty patients with vasculitis or systemic lupus erythematosus (SLE) due to commence MMF for active disease or remission maintenance were randomized to receive either 1440 mg/day MS or 2000 mg/day MMF (18 PSV, 2 SLE per group) in addition to corticosteroids. Random allocation was performed by minimization for age, diagnosis and renal function using a computer algorithm. Twenty-five were treated for active disease (5 first-line therapy, 20 salvage therapy) and 15 for remission maintenance. The composite primary end point was treatment failure and/or drug intolerance over 12 months. Treatment failure was defined as failure to achieve remission by 6 months or disease relapse and treatment intolerance was defined as inability to tolerate and maintain the target dose of MS or MMF within 12 months. RESULTS: Forty patients were included in the analyses. MS was associated with a lower primary end point rate [hazard ratio (HR) 0.37; 95% CI 0.17-0.80; P = 0.012] (11/20, 55% patients) compared with MMF (17/20, 85% patients). Treatment failure alone was less common in the MS group (HR 0.28; 95% CI 0.095-0.82; P = 0.020), although drug intolerance did not differ between groups (HR 0.53; 95% CI 0.20-1.42; P = 0.21). Despite randomization, patients in the MMF group may have had a higher baseline risk for treatment failure; more MMF patients had refractory disease and granulomatosis with polyangiitis (Wegener's). A glomerular filtration rate (GFR) ≤40 mL/min was associated with intolerance. Serious adverse events were common (55% MMF and 45% MS patients). CONCLUSIONS: No differences in treatment tolerance were observed between the MS and MMF groups. Despite similar treatment intolerance, MS was associated with improved efficacy in PSV and SLE compared with MMF. However, baseline group imbalances in factors potentially affecting remission and relapse may have influenced the results. Treatment intolerance was common and strongly associated with low GFR. Further treatment trials are warranted to investigate the effect of GFR on mycophenolic acid pharmacokinetics and clinical outcomes (ISRCTN83027184; EUDRACT 2005-002207-16; Funding Novartis UK)

Reducing prolonged sedentary time using a treadmill desk acutely improves cardiometabolic risk markers in male and female adults

The objectives of this study were to evaluate the acute effects of interrupting prolonged sitting with an accumulated 2 h of light-intensity walking on postprandial cardiometabolic risk markers. In this randomised crossover trial, 24 participants (twelve males) aged 18-55 years took part in two, 6.5 h conditions: 1) prolonged sitting (SIT) and 2) sitting interrupted hourly with 20 min light-intensity treadmill desk walking at between 1.2-3.5 km/h-1 (INT-SIT). Standardized meals were provided at 0 h and 3 h. Blood samples and blood pressure measures were taken hourly. Statistical analyses were completed using linear mixed models. Postprandial incremental area under the curve responses (mmol/L∙6.5 h) for glucose (4.52 [3.47, 5.56] and 6.66 [5.62, 7.71] for INT-SIT and SIT, respectively) and triglycerides (1.96 [0.96, 2.96] and 2.71 [1.70, 3.71] mmol/L∙6.5 h, for INT-SIT and SIT, respectively) were significantly lower in INT-SIT than SIT. Mean systolic and diastolic blood pressure responses were lower by 3% and 4%, respectively, in INT-SIT than SIT (P0.05). These findings suggest that interrupting sitting with an accumulated 2 h of light-intensity walking acutely improves cardiometabolic risk levels in males and females compared with prolonged sitting

The Weak Clustering of Gas-Rich Galaxies

We examine the clustering properties of HI-selected galaxies through an analysis of the HI Parkes All-Sky Survey Catalogue (HICAT) two-point correlation function. Various sub-samples are extracted from this catalogue to study the overall clustering of HI-rich galaxies and its dependence on luminosity, HI gas mass and rotational velocity. These samples cover the entire southern sky Dec < 0 deg, containing up to 4,174 galaxies over the radial velocity range 300-12,700 km/s. A scale length of r_0 = 3.45 +/- 0.25 Mpc/h and slope of gamma = 1.47 +/- 0.08 is obtained for the HI-rich galaxy real-space correlation function, making gas-rich galaxies among the most weakly clustered objects known. HI-selected galaxies also exhibit weaker clustering than optically selected galaxies of comparable luminosities. Good agreement is found between our results and those of synthetic HI-rich galaxy catalogues generated from the Millennium Run CDM simulation. Bisecting HICAT using different parameter cuts, clustering is found to depend most strongly on rotational velocity and luminosity, while the dependency on HI mass is marginal. Splitting the sample around v_rot = 108 km/s, a scale length of r_0 = 2.86 +/- 0.46 Mpc/h is found for galaxies with low rotational velocities compared to r_0 = 3.96 +/- 0.33 Mpc/h for the high rotational velocity sample.Comment: Accepted for publication in the Astrophysical Journa

Ecological Consequences of Shoreline Hardening: A Meta-Analysis

Protecting coastal communities has become increasingly important as their populations grow, resulting in increased demand for engineered shore protection and hardening of over 50% of many urban shorelines. Shoreline hardening is recognized to reduce ecosystem services that coastal populations rely on, but the amount of hardened coastline continues to grow in many ecologically important coastal regions. Therefore, to inform future management decisions, we conducted a meta-analysis of studies comparing the ecosystem services of biodiversity (richness or diversity) and habitat provisioning (organism abundance) along shorelines with versus without engineered-shore structures. Seawalls supported 23% lower biodiversity and 45% fewer organisms than natural shorelines. In contrast, biodiversity and abundance supported by riprap or breakwater shorelines were not different from natural shorelines; however, effect sizes were highly heterogeneous across organism groups and studies. As coastal development increases, the type and location of shoreline hardening could greatly affect the habitat value and functioning of nearshore ecosystems