Improving the Computation of Brier Scores for Evaluating Expert-Elicited Judgements

Structured expert judgement (SEJ) is a suite of techniques used to elicit expert predictions, e.g. probability predictions of the occurrence of events, for situations in which data are too expensive or impossible to obtain. The quality of expert predictions can be assessed using Brier scores and calibration questions. In practice, these scores are computed from data that may have a correlation structure due to sharing the effects of the same levels of grouping factors of the experimental design. For example, asking common questions from experts may result in correlated probability predictions due to sharing common question effects. Furthermore, experts commonly fail to answer all the needed questions. Here, we focus on (i) improving the computation of standard error estimates of expert Brier scores by using mixed-effects models that support design-based correlation structures of observations, and (ii) imputation of missing probability predictions in computing expert Brier scores to enhance the comparability of the prediction accuracy of experts. We show that the accuracy of estimating standard errors of expert Brier scores can be improved by incorporating the within-question correlations due to asking common questions. We recommend the use of multiple imputation to correct for missing data in expert elicitation exercises. We also discuss the implications of adopting a formal experimental design approach for SEJ exercises

Macro level insurance for financing post disaster recovery: The case of National Disaster Insurance Policy in Sri Lanka

This paper evaluates the use of macro-level insurance to finance post-disaster recovery and reinstatement by investigating the case of the National Disaster Insurance policy implemented by Sri Lanka. The national scheme provided cover for all properties in the country against hazards such as flooding and provided compensation for those affected. Analysis of secondary data obtained from the organisations that managed the scheme showed that the scheme has delivered a much higher return compared to the total insurance premium paid, suggesting that the scheme has delivered a net positive benefit compared to the cost of the premium and can be considered a viable option. However, the existing secondary data did not reveal the values of other costs and indirect benefits associated with the scheme to compute a meaningful benefit-to-cost ratio. Further rigorous, evidence-based cost-benefit analysis is required to assess the cost-effectiveness of a scheme of this nature. A cost-benefit analysis approach based on an analytical hierarchy process is proposed as a possible solution to assess the cost-effectiveness of the scheme, which could be used by government organisations as an alternative, where analytical and research resources may be limited, to evaluate a range of disaster recovery financing options using stakeholder opinion

Evaluation and Association Mapping of Resistance to Tan Spot and Stagonospora Nodorum Blotch in Adapted Winter Wheat Germplasm

Tan spot and Stagonospora nodorum blotch (SNB), often occurring together, are two economically significant diseases of wheat in the Northern Great Plains of the United States. They are caused by the fungi Pyrenophora tritici-repentis and Parastagonospora nodorum, respectively, both of which produce multiple necrotrophic effectors (NE) to cause disease. In this work, 120 hard red winter wheat (HRWW) cultivars or elite lines, mostly from the United States, were evaluated in the greenhouse for their reactions to the two diseases as well as NE produced by the two pathogens. One P. nodorum isolate (Sn4) and four Pyrenophora tritici-repentis isolates (Pti2, 331-9, DW5, and AR CrossB10) were used separately in the disease evaluations. NE sensitivity evaluation included ToxA, Ptr ToxB, SnTox1, and SnTox3. The numbers of lines that were rated highly resistant to individual isolates ranged from 11 (9%) to 30 (25%) but only six lines (5%) were highly resistant to all isolates, indicating limited sources of resistance to both diseases in the U.S. adapted HRWW germplasm. Sensitivity to ToxA was identified in 83 (69%) of the lines and significantly correlated with disease caused by Sn4 and Pti2, whereas sensitivity to other NE was present at much lower frequency and had no significant association with disease. As expected, association mapping located ToxA and SnTox3 sensitivity to chromosome arm 5BL and 5BS, respectively. A total of 24 potential quantitative trait loci was identified with −log (P value) \u3e 3.0 on 12 chromosomes, some of which are novel. This work provides valuable information and tools for HRWW production and breeding in the Northern Great Plains

The genotypes and virulence attributes of C. albicans isolates from oral leukoplakia

There is a debate as to whether some types of oral leucoplakias (OL) are caused by Candida species, and whether they contribute to the malignant transformation, associated with a minority of such lesions. As no detailed population analysis of yeast isolates from OL is available, we evaluated the virulence attributes, and genotypes of 35 C. albicans from OL, and compared their genotypes with 18 oral isolates from healthy individuals. The virulence traits evaluated were esterase, phospholipase, proteinase, haemolysin and coagulase production, and phenotypic switching activity, and yeast adherence and biofilm formation. DNA from OL and control yeasts were evaluated for A, B or C genotype status. Phospholipase, proteinase, and coagulase activity and biofilm formation was observed in 80%, 66%, 97 % and 77 % of the isolates, respectively. Phenotypic switching was detected in 8.6%, while heamolytic, and esterase activity and adherence were noted in all isolates. The genotype A was predominant amongst both the OL and control groups. Due to the small sample size of our study a larger investigation to define the role of candidal virulent attributes in the pathogenicity of OL is warranted, and the current data should serve as a basis until then

Copper-Heparin Inhalation Therapy To Repair Emphysema: A Scientific Rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration

Urea-Hydroxyapatite Nanohybrids for Slow Release of Nitrogen

While slow release of chemicals has been widely applied for drug delivery, little work has been done on using this general nanotechnology-based principle for delivering nutrients to crops. In developing countries, the cost of fertilizers can be significant and is often the limiting factor for food supply. Thus, it is important to develop technologies that minimize the cost of fertilizers through efficient and targeted delivery. Urea is a rich source of nitrogen and therefore a commonly used fertilizer. We focus our work on the synthesis of environmentally benign nanoparticles carrying urea as the crop nutrient that can be released in a programmed manner for use as a nanofertilizer. In this study, the high solubility of urea molecules has been reduced by incorporating it into a matrix of hydroxyapatite nanoparticles. Hydroxyapatite nanoparticles have been selected due to their excellent biocompatibility while acting as a rich phosphorus source. In addition, the high surface area offered by nanoparticles allows binding of a large amount of urea molecules. The method reported here is simple and scalable, allowing the synthesis of a urea-modified hydroxyapatite nanohybrid as fertilizer having a ratio of urea to hydroxyapatite of 6:1 by weight. Specifically, a nanohybrid suspension was synthesized by $\textit{in situ}$ coating of hydroxyapatite with urea at the nanoscale. In addition to the stabilization imparted due to the high surface area to volume ratio of the nanoparticles, supplementary stabilization leading to high loading of urea was provided by flash drying the suspension to obtain a solid nanohybrid. This nanohybrid with a nitrogen weight of 40% provides a platform for its slow release. Its potential application in agriculture to maintain yield and reduce the amount of urea used is demonstrated.Authors thank Hayleys Agro Ltd., Sri Lanka for initiating this research programme at SLINTEC and Nagarjuna Fertilizer and Chemical Ltd (NFCL), India for providing further support. Authors acknowledge Mr Sunanda Gunesekara of SLINTEC for assistance with scaling up the production process to enable the field trials. ARK acknowledges the financial support received from ICTPELETTRA Users Program, Trieste, Italy to conduct photoemission experiments at Materials Science beam line (MSB) and ELETTRA SRS on HA and urea coated HA samples. ARK further acknowledges Dr. R.G. Acres of MSB beam line for his extensive support to conduct photoemission experiments. We acknowledge the Department of Agriculture and Rice Research and Development Institute of Sri Lanka, in particular Dr Priyantha Weerasinghe, Mr D Sirisena and Dr Amitha Benthota for the assistance in carrying out pot and farmers filed trials. NFCL and Central Salt & Marine Chemicals Research Institute, Gujarat, India for TEM and BET analysis

Hospitalization in people with dementia with Lewy bodies: Frequency, duration, and cost implications

Introduction: Increased hospitalization is a major component of dementia impact on individuals and cost, but has rarely been studied in dementia with Lewy bodies (DLB). Our aim was to describe the risk and duration of hospital admissions in patients with DLB, and compare these to those in Alzheimer’s disease (AD) and the general population. Methods: A large database of mental health and dementia care in South London was used to assemble a cohort of patients diagnosed with DLB. These were 1:4 matched with patients diagnosed with AD on age, gender, and cognitive status. Results: Rates of hospital admissions in the year after dementia diagnosis were significantly higher in 194 patients with DLB than in 776 patients with AD (crude incidence rate ratio 1.50; 95% confidence interval: 1.28–1.75) or the catchment population (indirectly standardized hospitalization rate 1.22; 95% confidence interval: 1.06–1.39). Patients with DLB had on average almost four additional hospital days per person-year than patients with AD. Multivariate Poisson regression models indicated poorer physical health early in the disease course as the main driver of this increased rate of hospitalization, whereby neuropsychiatric symptoms additionally explained the higher number of hospital days. Discussion: Patients with DLB are more frequently admitted to general hospitals and utilize inpatient care to a substantially higher degree than patients with AD or the general elderly population. These data highlight an opportunity to reduce hospital days by identifying DLB earlier and providing more targeted care focused on the specific triggers for hospitalization and associations of prolonged stay

A Novel Statistic for Genome-Wide Interaction Analysis

Although great progress in genome-wide association studies (GWAS) has been made, the significant SNP associations identified by GWAS account for only a few percent of the genetic variance, leading many to question where and how we can find the missing heritability. There is increasing interest in genome-wide interaction analysis as a possible source of finding heritability unexplained by current GWAS. However, the existing statistics for testing interaction have low power for genome-wide interaction analysis. To meet challenges raised by genome-wide interactional analysis, we have developed a novel statistic for testing interaction between two loci (either linked or unlinked). The null distribution and the type I error rates of the new statistic for testing interaction are validated using simulations. Extensive power studies show that the developed statistic has much higher power to detect interaction than classical logistic regression. The results identified 44 and 211 pairs of SNPs showing significant evidence of interactions with FDR<0.001 and 0.001<FDR<0.003, respectively, which were seen in two independent studies of psoriasis. These included five interacting pairs of SNPs in genes LST1/NCR3, CXCR5/BCL9L, and GLS2, some of which were located in the target sites of miR-324-3p, miR-433, and miR-382, as well as 15 pairs of interacting SNPs that had nonsynonymous substitutions. Our results demonstrated that genome-wide interaction analysis is a valuable tool for finding remaining missing heritability unexplained by the current GWAS, and the developed novel statistic is able to search significant interaction between SNPs across the genome. Real data analysis showed that the results of genome-wide interaction analysis can be replicated in two independent studies