Ultra-relativistic thermal production of electrons and positrons

This thesis investigates ultra-relativistic processes of thermal production of electrons and positrons, and the theories involved in their description. It first focuses on collisional ionisation and excitation rates in a partially-ionised plasma, presenting correction factors to them that account for special relativity in the free electron motion as a function of temperature and the threshold energy. These results are extended to de-excitation and three body recombination using detailed balance. It then turns to the production of electron-positron pairs from Breit-Wheeler two-photon collision in the black-body field, and presents an analytic expression for the high-temperature limit of the total rate. It then examines the same physical process using the formalism of "external fields", in which the black-body is treated as as a thermal ensemble of classical field profiles. It presents a novel formal scheme for this calculation, and then presents the results of a numerical scheme that approximates this field ensemble by 1D spatial "Sauter pulses". It is found that pair-production calculated by this means exceeds that calculated by Breit-Wheeler by a large factor, and the energy spectrum of produced particles is presented. Then, work comparing different theoretical formalisms of vacuum-destabilising background fields in QED is presented. It is first shown how solving the Dirac equation with peculiar boundary conditions can give probability amplitudes for fermion scattering and pair creation/annihilation. It is then demonstrated for a broad class of external fields that four fermion propagators used in the literature are equivalent: Schwinger’s "proper-time” propagator; the "causal propagator” used in the "Bogoliubov transformation” method; and two defined using analytic continuation. To do so, we re-derive Schwinger’s proper-time expression for the propagator as a statement relating solutions of the inhomogeneous Dirac equation to those of the inhomogeneous "proper-time Dirac equation”. We then show that all four propagators return solutions of the inhomogeneous Dirac equation that satisfy the same boundary condition.Open Acces

Multiple imputation of missing covariates for the Cox proportional hazards cure model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134146/1/sim7048_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134146/2/sim7048.pd

SNPs in lncRNA regions and breast cancer risk

Peer reviewe

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Càncer de mama; Genètica del càncer; Factors de riscCáncer de mama; Genética del cáncer; Factores de riesgoBreast cancer; Cancer genetics; Risk factorsBreast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

&lt;b&gt;Objective&lt;/b&gt; &lt;i&gt;ABCB1&lt;/i&gt; encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; The best candidates from fine-mapping analysis of 21 &lt;i&gt;ABCB1&lt;/i&gt; SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt; Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, &lt;i&gt;ABCB1&lt;/i&gt; expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; Our study represents the largest analysis of &lt;i&gt;ABCB1&lt;/i&gt; SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.&lt;p&gt;&lt;/p&gt