Data Integration Model for Air Quality: A Hierarchical Approach to the Global Estimation of Exposures to Ambient Air Pollution

This is the author accepted manuscript. Available from arXiv via the URL in this record.Air pollution is a major risk factor for global health, with both ambient and household air pollution contributing substantial components of the overall global disease burden. One of the key drivers of adverse health effects is fine particulate matter ambient pollution (PM2:5) to which an estimated 3 million deaths can be attributed annually. The primary source of information for estimating exposures has been measurements from ground monitoring networks but, although coverage is increasing, there remain regions in which monitoring is limited. Ground monitoring data therefore needs to be supplemented with information from other sources, such as satellite retrievals of aerosol optical depth and chemical transport models. A hierarchical modelling approach for integrating data from multiple sources is proposed allowing spatially-varying relationships between ground measurements and other factors that estimate air quality. Set within a Bayesian framework, the resulting Data Integration Model for Air Quality (DIMAQ) is used to estimate exposures, together with associated measures of uncertainty, on a high resolution grid covering the entire world. Bayesian analysis on this scale can be computationally challenging and here approximate Bayesian inference is performed using Integrated Nested Laplace Approximations. Model selection and assessment is performed by cross-validation with the final model offering substantial increases in predictive accuracy, particularly in regions where there is sparse ground monitoring, when compared to previous approaches: root mean square error (RMSE) reduced from 17.1 to 10.7, and population weighted RMSE from 23.1 to 12.1 gm3. Based on summaries of the posterior distributions for each grid cell, it is estimated that 92% of the world’s population reside in areas exceeding the World Health Organization’s Air Quality Guidelines.Matthew Lloyd Thomas is supported by a scholarship from the EPSRC Centre for Doctoral Training in Statistical Applied Mathematics at Bath (SAMBa), under the project EP/L015684/1. Amelia Jobling was supported for this work by WHO contracts APW 201255146 and 201255393

Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice

Pre-existing immunity to human adenovirus serotype 5 (Ad5) is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M.), nasal (I.N.) or oral (P.O.) route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-γ+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-γ+ CD8+ T cells (3.9±1% naïve vs. 3.6±1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40±10 reciprocal dilution, both groups). The number of INF-γ+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL) after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146±14, naïve vs. 120±16 SFC/million MNCs, PEI). However, pre-existing immunity reduced NAB levels in BAL by ∼25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-γ+ CD8+ T cells 10 days after administration (0.3±0.3% PEG vs. 1.7±0.5% unmodified). PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine

The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden

Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review

Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE). In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter). Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias, healthcare access) between environmental drivers/exposures and disease detection. Key areas of future research include: disentangling the complex effects of weather/climate on each exposure-health outcome pathway (e.g. person-to-person vs environment-to-person), and linking weather data to individual cases longitudinally

Evaluation of calcium silicate cement bond strength after using gutta-percha solvents

Objectives: To determine the effect of different gutta-percha solvents (chloroform, Endosolv E, orange oil, and eucalyptol) on the push-out bond strength of calcium silicate cements (CSCs; white mineral trioxide aggregate [WMTA]; capsule-form mineral trioxide aggregate [CMTA], and Biodentine).Materials and Methods: One hundred and fifty extracted single-rooted human mandibular premolars were sectioned into 3-mm-thick slices. The canal lumens were enlarged for 1.35-mm-diameter standardized cavities. The samples were randomly divided into five groups (n = 30) according to the solvent type: G1, chloroform; G2, Endosolv E; G3, eucalyptol; G4, orange oil; G5, no solvent (control). After application of the solvents for 5 min, the specimens were divided into three subgroups (n = 10): (i) WMTA, (ii) CMTA, and (iii) Biodentine. The push-out bond strength was measured. Two-way ANOVA analysis of variance and post hoc Tukey tests were used for analyses (P = 0.05). Results: The highest push-out bond strength was observed in the Biodentine (P < 0.05), and the values of WMTA and CMTA were not significantly different in all solvent groups (P > 0.05). There were no statistically significant differences among the gutta-percha solvents and control group in WMTA (P > 0.05).Conclusions: Gutta-percha solvents used during retreatment decreased the bond strength of Biodentine and CMTA to root dentin. The bond strength of WMTA was not affected by the use of gutta-percha solvents.Keywords: Biodentine, gutta-percha solvent, MTA, push out bond strengt

613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture