Flood Events:Extreme Value Problems and Efficient Estimation of Loss

Widespread flood events have heavy consequences on society and the environment. Gaining insight into the occurrence and impact of these rare flood events is thus of interest to many parties such as governments, environmental organisations and insurance companies. To assess flood risk, past events are studied and used to t statistical models from which plausible flood events are simulated over large areas and large periods of time. These simulated extreme events then drive other models, such as models of loss for insurance purposes, to provide insight into the possible impact of future flood events. This thesis addresses problems in the analysis of extreme river flows which cause flooding, and the inefficiency of simulation of yearly loss due to flooding. Firstly, many extreme value analyses are conducted in reaction to the occurrence of a large flooding event. This timing of the analysis introduces bias and poor coverage probabilities into the associated risk assessments subsequently leading to over-designed flood protection schemes. These problems are explored through studying stochastic stopping criteria and new likelihood-based inferences are proposed that mitigate against these difficulties. Simulated extreme events are used along with geographical knowledge and property information to simulate losses at each property for each flood event over many years. These simulations are then aggregated to obtain total yearly losses and to estimate return levels of yearly loss. The large number of simulations needed makes this process computationally expensive. A new method is proposed, using novel concentration inequalities, which reduces the number of years that need to be simulated. Finally, modelling extreme flood events is complicated due to temporal dependence and the spatial dependencies of river flows between multiple locations with the presence of time lags between locations. The theory of multivariate temporally dependent extremes is explored, with focus on measures of dependence, and areas of further research are highlighted

High Power Cyclotrons for the Neutrino Experiments DAEδALUS and IsoDAR

DAEδALUS (Decay At rest Experiment for δcp At a Laboratory for Underground Science) has been proposed to measure the value of the CP violating phase delta through the oscillation of low energy muon anti-neutrinos to electron antineutrinos. With a single large detector, three accelerators at different distances enable the oscillation to be measured with sufficient accuracy. We have proposed the superconducting multi-megawatt DAEδALUS Supercinducting Ring Cyclotron (DSRC) as the means of producing the 800 MeV 12 mA protons required, through the acceleration of H2+, ions with highly efficient stripping extraction. The DSRC comprises twin ion sources and injector cyclotrons, followed by a booster. The injector cyclotron can also be used for a separate experiment, IsoDAR (Isotope Decay At Rest) in which low energy protons produce Lithium 8, and thus a very pure electron antineutrino source which can be used to measure, or rule out, short range oscillation to a sterile neutrino. We describe recent developments in the designs of the injector and the booster, and the prospects for the two experiments

Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages.

Background - Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants which can recruit alveolar macrophages to sites of particle deposition. The aim of this study was to assess the responses of a type II epithelial cell line (L-2) to both fine and nanoparticle exposure in terms of secretion of chemotactic substances capable of inducing macrophage migration.ResultsExposure of type II cells to carbon black nanoparticles resulted in significant release of macrophage chemoattractant compared to the negative control and to other dusts tested (fine carbon black and TiO2 and nanoparticle TiO2) as measured by macrophage migration towards type II cell conditioned medium. SDS-PAGE analysis of the conditioned medium from particle treated type II cells revealed that a higher number of protein bands were present in the conditioned medium obtained from type II cells treated with nanoparticle carbon black compared to other dusts tested. Size-fractionation of the chemotaxin-rich supernatant determined that the chemoattractants released from the epithelial cells were between 5 and 30 kDa in size.ConclusionThe highly toxic nature and reactive surface chemistry of the carbon black nanoparticles has very likely induced the type II cell line to release pro-inflammatory mediators that can potentially induce migration of macrophages. This could aid in the rapid recruitment of inflammatory cells to sites of particle deposition and the subsequent removal of the particles by phagocytic cells such as macrophages and neutrophils. Future studies in this area could focus on the exact identity of the substance(s) released by the type II cells in response to particle exposure

A Bayesian spatio-temporal model for precipitation extremes - STOR team contribution to the EVA2017 challenge

This paper concerns our approach to the EVA2017 challenge, the aim of which was to predict extreme precipitation quantiles across several sites in the Netherlands. Our approach uses a Bayesian hierarchical structure, which combines Gamma and generalised Pareto distributions. We impose a spatio-temporal structure in the model parameters via an autoregressive prior. Estimates are obtained using Markov chain Monte Carlo techniques and spatial interpolation. This approach has been successful in the context of the challenge, providing reasonable improvements over the benchmark

Modelling the potential for parenting skills interventions to reduce inequalities and population prevalence of children’s mental health problems: evidence from the Millennium Cohort Study

Parenting programmes can improve parenting quality and, in turn, children's mental health. If scaled-up, they have the potential to reduce population inequalities and prevalence in child mental health problems (MHP). However, this cannot be investigated with trials. Using data from the UK Millennium Cohort Study (18,000 children born 2000–2002), we simulated population impact of scale-up of seven parenting programmes. Predicted probabilities of child MHP (Strengths and Difficulties Questionnaire) by household income quintile (Risk ratios [RRs] and differences [RDs], 95% confidence intervals [CI]) were estimated from logistic marginal structural models, adjusting for parenting quality scores (Child-Parent Relationship Scale at 3 years) and confounders. The impact of scaling-up parenting programmes was simulated by re-estimating predicted probabilities of child MHP after increasing parenting scores according to intervention intensity, targeting mechanisms and programme uptake levels. Analyses included data from 14,399 children, with survey weights and multiple imputation addressing sampling design, attrition and item missingness. Prevalence of child MHP at 5 years was 11.3% (11.4% unadjusted), with relative and absolute income inequalities (RR = 4.8[95%CI:3.6–5.9]; RD = 15.8%[13.4–18.2]). In simulations, universal, non-intensive parenting programmes reduced prevalence (9.4%) and absolute inequalities (RR = 5.0[95%CI:3.8–6.2]; RD = 13.6%[11.5–15.7]). Intensive programmes, targeting a range of potential risk criteria (e.g. receipt of means-tested benefits), reduced inequalities (RR = 4.0[95%CI:3.0–4.9]; RD = 12.4%[10.3–14.6] and, to a lesser extent, prevalence (10.3%). By simulating implementation of parenting programmes, we show that universal non-intensive and targeted intensive approaches have the potential to reduce child MHP at population level, and to reduce but not eliminate inequalities, with important implications for future policy and practice

Antioxidant, Anticancer and Antimicrobial, Effects of Rubia cordifolia Aqueous Root Extract

Received 15th October 2015 Accepted 29th October 2015 Published 10th November 2015Aims: To evaluate the total antioxidant capacity (TAC) of Rubia cordifolia root extracts, to test anticancer activity against MDA-MB-231 breast cancer cell lines, and to evaluate antimicrobial activity of the same extract versus six Gram-positive and negative bacteria. Study Design: In vitro. Place of Study and Duration: School of Biomedical Sciences, Ulster University, July 2014-Sept 2015. Methodology: TAC was tested using ABTS, DPPH, FRAP and Folin assays and values were expressed as mg-gallic acid equivalents per 100 g (GAE/100 g) of sample. Anticancer properties were examined against MDA-MB-231 breast cancer cell lines using Sulforhodamine B assay. Antimicrobial activity was examined using a disk diffusion assay with three Gram-positive (Staphylococcus epidermidis, Staphylococcus aureus and Bacillus cereus) and three Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi) bacteria. Results: TAC of dry extracts of Rubia cordifolia ranged from 523±43 to 4513±208 (mg GAE mg/100 g) depending on the method of analysis, ABTS> FRAP> Folin > DPPH methods. R. cordifolia dry extract showed cytotoxicity against MDA-MB-231 with IC50 = 44 µg/ml or 5.1µM GAE. No antimicrobial activity was observed against the three Gram-positive, or three Gram-negative bacterial species using the water extract or R. cordifolia. Conclusion: R. cordifolia aqueous extract possess high total antioxidant capacity but values depend on the method of analysis. R. cordifolia extract inhibits MDA-MB-231 breast cancer cells proliferation but nil anti-bacterial activity was observed for three Gram-positive and three Gram-negative bacterial strains tested

Murine factor H co-produced in yeast with protein disulfide isomerase ameliorated C3 dysregulation in factor H-Deficient mice

Recombinant human factor H (hFH) has potential for treating diseases linked to aberrant complement regulation including C3 glomerulopathy (C3G) and dry age-related macular degeneration. Murine FH (mFH), produced in the same host, is useful for pre-clinical investigations in mouse models of disease. An abundance of FH in plasma suggests high doses, and hence microbial production, will be needed. Previously, Pichia pastoris produced useful but modest quantities of hFH. Herein, a similar strategy yielded miniscule quantities of mFH. Since FH has 40 disulfide bonds, we created a P. pastoris strain containing a methanol-inducible codon-modified gene for protein-disulfide isomerase (PDI) and transformed this with codon-modified DNA encoding mFH under the same promoter. What had been barely detectable yields of mFH became multiple 10s of mg/L. Our PDI-overexpressing strain also boosted hFH overproduction, by about tenfold. These enhancements exceeded PDI-related production gains reported for other proteins, all of which contain fewer disulfide-stabilized domains. We optimized fermentation conditions, purified recombinant mFH, enzymatically trimmed down its (non-human) N-glycans, characterised its functions in vitro and administered it to mice. In FH-knockout mice, our de-glycosylated recombinant mFH had a shorter half-life and induced more anti-mFH antibodies than mouse serum-derived, natively glycosylated, mFH. Even sequential daily injections of recombinant mFH failed to restore wild-type levels of FH and C3 in mouse plasma beyond 24 hours after the first injection. Nevertheless, mFH functionality appeared to persist in the glomerular basement membrane because C3-fragment deposition here, a hallmark of C3G, remained significantly reduced throughout and beyond the ten-day dosing regimen