Estimation of Parameters in DNA Mixture Analysis

In Cowell et al. (2007), a Bayesian network for analysis of mixed traces of DNA was presented using gamma distributions for modelling peak sizes in the electropherogram. It was demonstrated that the analysis was sensitive to the choice of a variance factor and hence this should be adapted to any new trace analysed. In the present paper we discuss how the variance parameter can be estimated by maximum likelihood to achieve this. The unknown proportions of DNA from each contributor can similarly be estimated by maximum likelihood jointly with the variance parameter. Furthermore we discuss how to incorporate prior knowledge about the parameters in a Bayesian analysis. The proposed estimation methods are illustrated through a few examples of applications for calculating evidential value in casework and for mixture deconvolution

Resonances in a spring-pendulum: algorithms for equivariant singularity theory

A spring-pendulum in resonance is a time-independent Hamiltonian model system for formal reduction to one degree of freedom, where some symmetry (reversibility) is maintained. The reduction is handled by equivariant singularity theory with a distinguished parameter, yielding an integrable approximation of the Poincaré map. This makes a concise description of certain bifurcations possible. The computation of reparametrizations from normal form to the actual system is performed by Gröbner basis techniques.

Modelling with non-stratified chain event graphs

© 2019, Springer Nature Switzerland AG. Chain Event Graphs (CEGs) are recent probabilistic graphical modelling tools that have proved successful in modelling scenarios with context-specific independencies. Although the theory underlying CEGs supports appropriate representation of structural zeroes, the literature so far does not provide an adaptation of the vanilla CEG methods for a real-world application presenting structural zeroes also known as the non-stratified CEG class. To illustrate these methods, we present a non-stratified CEG representing a public health intervention designed to reduce the risk and rate of falling in the elderly. We then compare the CEG model to the more conventional Bayesian Network model when applied to this setting

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

Oral capecitabine (Xeloda<sup>®</sup>) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK

Quenching of Weak Interactions in Nucleon Matter

We have calculated the one-body Fermi and Gamow-Teller charge-current, and vector and axial-vector neutral-current nuclear matrix elements in nucleon matter at densities of 0.08, 0.16 and 0.24 fm$^{-3}$ and proton fractions ranging from 0.2 to 0.5. The correlated states for nucleon matter are obtained by operating on Fermi-gas states by a symmetrized product of pair correlation operators determined from variational calculations with the Argonne v18 and Urbana IX two- and three-nucleon interactions. The squares of the charge current matrix elements are found to be quenched by 20 to 25 % by the short-range correlations in nucleon matter. Most of the quenching is due to spin-isospin correlations induced by the pion exchange interactions which change the isospins and spins of the nucleons. A large part of it can be related to the probability for a spin up proton quasi-particle to be a bare spin up/down proton/neutron. We also calculate the matrix elements of the nuclear Hamiltonian in the same correlated basis. These provide relatively mild effective interactions which give the variational energies in the Hartree-Fock approximation. The calculated two-nucleon effective interaction describes the spin-isospin susceptibilities of nuclear and neutron matter fairly accurately. However $\geq$ 3-body terms are necessary to reproduce the compressibility. All presented results use the simple 2-body cluster approximation to calculate the correlated basis matrix elements.Comment: submitted to PR

Understanding and reducing sexual prejudice in Jamaica: Theoretical and practical insights from a severely anti-gay society

Jamaica has earned an international reputation for severe sexual prejudice: perhaps disproportionately so compared to other severely anti-LGBT societies. Until recently, however, no quantitative empirical research had investigated Jamaica’s sexual prejudice, leaving the prejudice poorly understood and methods of reducing it unclear. This article reviews the past 15 years of empirical research on Jamaican anti-LGBT prejudice. It situates Jamaica within the global context, explains the current understanding of the severity and nature of the problem, evaluates solutions currently being explored and suggests promising strategies based on available evidence. Importantly, this article also reflects on lessons learned from Jamaica that are relevant for other severely anti-LGBT societies

Cold Bose gases with large scattering lengths

We calculate the energy and condensate fraction for a dense system of bosons interacting through an attractive short range interaction with positive s-wave scattering length $a$. At high densities, $n>>a^{-3}$, the energy per particle, chemical potential, and square of the sound speed are independent of the scattering length and proportional to $n^{2/3}$, as in Fermi systems.Comment: 4 pages, 3 figure

Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York

High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35–134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer