Modelling inflation with a power-law approach to the inflationary plateau

A new family of inflationary models is introduced and analyzed. The behavior of the parameters characterizing the models suggest preferred values, which generate the most interesting testable predictions. Results are further improved if late reheating and/or a subsequent period of thermal inflation is taken into account. Specific model realizations consider a sub-Planckian inflaton variation or a potential without fine-tuning of mass scales, based on the Planck and grand unified theory scales. A toy model realization in the context of global and local supersymmetry is examined, and results fitting the Planck observations are determined

The universe during epochs of accelerating expansion

Cosmic inflation, the accelerated expansion of the early Universe, is an accepted pillar in the foundations of modern cosmology. This is due mainly to its success at explaining several anomalies between observations and the existing Hot Big Bang model of the Universe, but a specific model is not agreed upon in the literature. The Universe has also recently been observed to enter another phase of accelerating expansion, driven by an unexplained mechanism called ‘dark energy’. The research presented in this thesis grows organically; starting with an investigation into novel inflationary models and developing into quintessential inflation models. The latter explain both the primordial inflation and dark energy observations using one minimal framework. A new family of inflation models is presented, which excellently match observations for natural parameter values, and a derivation from supergravity is demonstrated. A period of thermal inflation allows the supergravity realisation of hybrid inflation to be realigned with observations. A new approach to inflection-point inflation is developed, which is considerably less fine-tuned and exotic than previous models. Two novel quintessential inflation models are introduced, the first embedded in α-attractors - a compelling framework of inflationary model building and the second in Gauss-Bonnet gravity - an extension to General Relativity. Detailed investigations of reheating after inflation are undertaken, focusing on gravitational reheating and instant preheating, analysing the necessary constraints including those from supergravity. Along the way, there is a brief diversion into primordial black holes, investigating how a slow reheating period affects their formation rates

A systematic review of geographical variation in access to chemotherapy

BACKGROUND: Rising cancer incidence, the cost of cancer pharmaceuticals and the introduction of the Cancer Drugs Fund in England, but not other United Kingdom(UK) countries means evidence of ‘postcode prescribing’ in cancer is important. There have been no systematic reviews considering access to cancer drugs by geographical characteristics in the UK. METHODS: Studies describing receipt of cancer drugs, according to healthcare boundaries (e.g. cancer network [UK]) were identified through a systematic search of electronic databases and grey literature. Due to study heterogeneity a meta-analysis was not possible and a narrative synthesis was performed. RESULTS: 8,780 unique studies were identified and twenty-six included following a systematic search last updated in 2015. The majority of papers demonstrated substantial variability in the likelihood of receiving chemotherapy between hospitals, health authorities, cancer networks and UK countries (England and Wales). After case-mix adjustment, there was up to a 4–5 fold difference in chemotherapy utilisation between the highest and lowest prescribing cancer networks. There was no strong evidence that rurality or distance travelled were associated with the likelihood of receiving chemotherapy and conflicting evidence for an effect of travel time. CONCLUSIONS: Considerable variation in chemotherapy prescribing between healthcare boundaries has been identified. The absence of associations with natural geographical characteristics (e.g. rurality) and receipt of chemotherapy suggests that local treatment habits, capacity and policy are more influential. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-2026-y) contains supplementary material, which is available to authorized users

An investigation into the impact of microvascular leakage on neutrophil transendothelial migration as analysed using murine models of inflammation.

PhD ThesisControlled opening of endothelial-cell (EC) junctions is vital in regulating vascular permeability and neutrophil transendothelial migration (TEM) during acute inflammation. Although both phenomena can occur independently, as supported by distinct molecular pathways, the potential inter-play of these two responses requires further exploration. In this thesis, we investigated the impact of microvascular leakage on neutrophil TEM and the potential downstream pathophysiological consequences. To this aim, as part of this project, a confocal intravital microscopy platform was developed for simultaneous analysis of neutrophil TEM and vascular permeability within the murine cremaster muscle microcirculation. The inflammatory reactions employed were driven by locally administered LTB4, or IL-1β ± vasoactive agents (e.g. histamine/VEGF), or by a model of IR-injury. The findings provide direct evidence for the ability of inflammatory reactions characterised by enhanced microvascular leakage to promote an aberrant mode of neutrophil TEM, known as reverse (r)TEM. This response is characterised by neutrophils that have partially breached the endothelium and move in a retrograde mode, thus returning into the lumen. Interestingly, genetic functional deficiency or pharmacological blockade of VE-cadherin-dependent hyper-permeability reduced the frequency of neutrophil rTEM. Mechanistically, this migration behaviour was driven by excessive diffusion of tissue-derived CXCL1 through EC junctions into the plasma, resulting in a disrupted chemotactic gradient across the endothelium. Development of a novel tracking method allowed us to demonstrate that rTEM neutrophils exhibited a pro-inflammatory phenotype and disseminated into the blood and lung circulation. Presence of these cells in lungs was associated with vascular damage. Finally, we identified distinct roles for TNF-receptors in controlling vascular permeability and neutrophil migration during IR-injury. Collectively, the findings of this thesis provide a causal link between increased local microvascular leakage induction and disrupted localisation of chemotactic directional cues across the endothelial barrier, resulting in aberrant mode of neutrophil migration and subsequent distant organ damage

The benefit of a tough skin: Bullet holes, weathering and the preservation of heritage

© 2017 The Authors. Projectile damage to building stone is a widespread phenomenon. Sites damaged 100 years ago during the First World War still see daily use, while in a more contemporary setting numerous reports show the damage to buildings in Babylon, Mosul and Palmyra. While research has been carried out on the long-term effects of conflict such as fire damage, little is known about the protracted damage sustained through the impact of bullets, shrapnel and other metal projectiles outside of the field of engineering focused on ceramics and metals. To investigate alterations to mineral structure caused by projectile damage, impacts were created in medium-grained, well-compacted, mesoporous sandstone samples using 0.22 calibre lead bullets shot at a distance of 20 m. Half these samples were treated with a surface consolidant (Wacker OH 100), to mimic natural cementation of the rock surface. These samples were then tested for changes to surface hardness and moisture movement during temperature cycles of 15–65°C. Petrographic thin section analysis was carried out to investigate the micro-scale deformation associated with high-speed impact. The results surprisingly show that stress build-up behind pre-existing cementation of the surface, as found in heritage sites that have been exposed to moisture and temperature fluctuations for longer periods of time, can be alleviated with a bullet impact

Using DNA Metabarcoding to Characterize the Prey Spectrum of Two Co-Occurring Themisto Amphipods in the Rapidly Changing Atlantic-Arctic Gateway Fram Strait

The two congeneric hyperiids Themisto libellula and T. abyssorum provide an important trophic link between lower and higher trophic levels in the rapidly changing Arctic marine ecosystem. These amphipods are characterized by distinct hydrographic affinities and are hence anticipated to be impacted differently by environmental changes, with major consequences for the Arctic food web. In this study, we applied DNA metabarcoding to the stomach contents of these Themisto species, to comprehensively reveal their prey spectra at an unprecedented-high-taxonomic-resolution and assess the regional variation in their diet across the Fram Strait. Both species feed on a wide variety of prey but their diet strongly differed in the investigated summer season, showing overlap for only a few prey taxa, such as calanoid copepods. The spatially structured prey field of T. libellula clearly differentiated it from T. abyssorum, of which the diet was mainly dominated by chaetognaths. Our approach also allowed the detection of previously overlooked prey in the diet of T. libellula, such as fish species and gelatinous zooplankton. We discuss the reasons for the differences in prey spectra and which consequences these may have in the light of ongoing environmental changes

Quintessential inflation with a trap and axionic dark matter

We study a new model of quintessential inflation which is inspired by supergravity and string theory. The model features a kinetic pole, which gives rise to the inflationary plateau, and a runaway quintessential tail. We envisage a coupling between the inflaton and the Peccei-Quinn (PQ) field which terminates the roll of the runaway inflaton and traps the latter at an enhanced symmetry point (ESP), thereby breaking the PQ symmetry. The kinetic density of the inflaton is transferred to the newly created thermal bath of the hot big bang due to the decay of PQ particles. The model successfully accounts for the observations of inflation and dark energy with natural values of the model parameters, while also resolving the strong CP problem of QCD and generating axionic dark matter, without isocurvature perturbations. Trapping the inflaton at the ESP ensures that the model does not suffer from the infamous 5th force problem, which typically plagues quintessence

Loop inflection-point inflation

A novel inflection-point inflation model is analysed. The model considers a massless scalar field, whose self-coupling’s running is stabilised by a non-renormalisable operator. The running is controlled by a fermion loop. We find that successful inflation is possible for a natural value of the Yukawa coupling y≃4×10^{−4}. The necessary fine-tuning is only ∼10^{−6}, which improves on the typical tuning of inflection-point inflation models, such as MSSM inflation. The model predicts a spectral index within the 1-σ bound of the latest CMB observations, with a very small negative running, and negligible tensors (r∼10^{−(9−10)}). These results are largely independent of the order of the stabilising non-renormalisable operator

Equity of access to treatment on the Cancer Drugs Fund:A missed opportunity for cancer research?

AbstractUsing mixed-methods, we investigated the CDF in the South West of England (3193 cancer patients treated through the CDF, April 1st 2011–March 31st 2013) for evidence of: (1) equitable access across socioeconomic groups, age groups, sex, and Cancer Network; (2) time-to-treatment by socioeconomic group; and (3) the perception of the CDF as fair, using semi-structured interviews with oncology consultants.There was no evidence of inequitable access to anti-cancer therapy for those in more deprived areas. For all cancer types, there was a lower proportion of women in the CDF cohort than in the Cancer Registry reference population (e.g., melanoma, CDF 36.8% female, reference population 48.7%; difference 11.9%, 95% CI 3.1–20.7%). There was a lower proportion of older patients in the CDF compared with the reference population (e.g., colorectal cancer, CDF 6.9% ≥80 years, reference population 30.1%; difference 23.2%, 95% CI 20.2–26.2%). Interviewed oncologists felt differences in performance status, not age, influenced referral to the CDF, with neither deprivation, nor gender contributing.Our study suggests that the CDF has differential access by age and sex, but not by deprivation. The absence of high quality CDF data represents a missed opportunity to fully evaluate equity of access and the real-world costs and outcomes of novel anti-cancer drugs

Instant preheating in quintessential inflation with α-attractors

We investigate a compelling model of quintessential inflation in the context of α-attractors, which naturally result in a scalar potential featuring two flat regions; the inflationary plateau and the quintessential tail. The “asymptotic freedom” of α-attractors, near the kinetic poles, suppresses radiative corrections and interactions, which would otherwise threaten to lift the flatness of the quintessential tail and cause a 5th force problem respectively. Since this is a nonoscillatory inflation model, we reheat the Universe through instant preheating. The parameter space is constrained by both inflation and dark energy requirements. We find an excellent correlation between the inflationary observables and model predictions, in agreement with the α-attractors setup. We also obtain successful quintessence for natural values of the parameters. Our model predicts potentially sizeable tensor perturbations (at the level of 1%) and a slightly varying equation of state for dark energy, to be probed in the near future