The optimization of image guided radiotherapy in lung cancer

The hypothesis of this work was whether IGRT could be safely implemented for clinical use in a busy oncology centre. I aimed to study a number of questions that remain unresolved in the current literature regarding safe and optimised implementation of IGRT techniques. The first study undertaken was the calculation of a local set up margin using two widely recognised margin recipes. This involved the assessment and analysis of multiple images belonging to 100 patients. This allowed progression onto the next project which was assessment of the optimal safe method of delineation of 4DCT. The most efficient method was compared to gold standard. At this point a different aspect of the radiation process was assessed, namely verification. A feasibility study of a simple, efficient form of imaging for use in review of a particular error was performed. This also involved the use of a novel tool which required independent assessment. This progressed into a further study of a larger number of patients using this tool and the images assessed previously to verify a novel form of radiation delivery. Lastly a planning study was performed to quantify the clinical benefit of another delivery system. This involved the delineation and planning of a large number of radical lung patients with standard radiation treatment and the novel radiation treatment and an assessment of the potential clinical benefits. The work presented in this thesis has answered some specific questions in IGRT in lung cancer, and contributed both locally and in the wider lung cancer community to increasing the use of IGRT in lung cancer

Modeling early haematologic adverse events in conformal and intensity-modulated pelvic radiotherapy in anal cancer

AbstractBackground and purposeTo determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+).Methods and materialsTwo groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats).Percent volume of PBM and sub structures receiving 5–25Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed.ResultsPMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p<0.05).ConclusionWhilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling

Attaining Doppler Precision of 10 cm s^(-1) with a Lock-in Amplified Spectrometer

We explore the radial velocity performance benefits of coupling starlight to a fast-scanning interferometer and a fast-readout spectrometer with zero readout noise. By rapidly scanning an interferometer, we can decouple wavelength calibration errors from precise radial velocity measurements, exploiting the advantages of lock-in amplification. In a Bayesian framework, we investigate the correlation between wavelength calibration errors and resulting radial velocity errors. We construct an end-to-end simulation of this approach to address the feasibility of achieving 10 cm s^(-1) radial velocity precision on a typical Sun-like star using existing, 5 m-class telescopes. We find that such a precision can be reached in a single night, opening up possibilities for ground-based detections of Earth-Sun analog systems

Niche specialization of reef-building corals in the mesophotic zone: metabolic trade-offs between divergent Symbiodinium types

The photobiology of two reef corals and the distribution of associated symbiont types were investigated over a depth gradient of 0–60 m at Scott Reef, Western Australia. Pachyseris speciosa hosted mainly the same Symbiodinium C type similar to C3 irrespective of sampling depth. By contrast, Seriatopora hystrix hosted predominantly Symbiodinium type D1a or D1a-like at shallow depths while those in deeper water were dominated by a Symbiodinium C type closely related to C1. The photosynthesis/respiration (P/R) ratio increased consistently with depth at the two sampling times (November 2008 and April 2009) for P. speciosa and in November 2008 only for S. hystrix, suggesting a reduction in metabolic energy expended for every unit of energy obtained from photosynthesis. However, in April 2009, shallow colonies of S. hystrix exhibited decreased P/R ratios down to depths of approximately 23 m, below which the ratio increased towards the maximum depth sampled. This pattern was mirrored by changes in tissue biomass determined as total protein content. The depth of change in the direction of the P/R ratio correlated with a shift from Symbiodinium D to C-dominated colonies. We conclude that while photobiological flexibility is vital for persistence in contrasting light regimes, a shift in Symbiodinium type may also confer a functional advantage albeit at a metabolic cost with increased depth

Falkland Island peatland development processes and the pervasive presence of fire

Acknowledgments RJP secured funding for this research from the Quaternary Research Association, University of York and the Russian Science Foundation (19-14-00102). We thank Paul Brickle and other members of the South Atlantic Environmental Research Institute for their help with logistics, David Large for valuable discussions about Falkland Islands peat and all landowners for access permission. This work is dedicated to Richard J. Payne who was tragically killed while climbing Peak 6477, a previously unclimbed subsidiary peak of Nanda Devi (Garhwal Himalayas) in May 2019. CRediT authorship contribution statement Dmitri Mauquoy: Conceptualization, Investigation, Writing - original draft, Writing - review & editing. Richard J. Payne: Conceptualization, Investigation. Kirill V. Babeshko: Investigation, Writing - original draft, Writing - review & editing. Rebecca Bartlett: Investigation, Writing - original draft, Writing - review & editing. Ian Boomer: Investigation. Hannah Bowey: Investigation. Chris D. Evans: Conceptualization, Writing - original draft, Writing - review & editing. Fin Ring-Hrubesh: Investigation. David Muirhead: Methodology, Investigation, Writing - original draft, Writing - review & editing. Matthew O’Callaghan: Investigation. Natalia Piotrowska: Investigation. Graham Rush: Investigation. Thomas Sloan: Investigation. Craig Smeaton: Methodology, Investigation, Writing - original draft. Andrey N. Tsyganov: Investigation, Writing - original draft, Writing - review & editing. Yuri A. Mazei: Investigation, Writing - original draft, Writing - review & editing.Peer reviewedPostprin

High-resolution genomic analysis to investigate the impact of the invasive brushtail possum (Trichosurus vulpecula) and other wildlife on microbial water quality assessments.

Escherichia coli are routine indicators of fecal contamination in water quality assessments. Contrary to livestock and human activities, brushtail possums (Trichosurus vulpecula), common invasive marsupials in Aotearoa/New Zealand, have not been thoroughly studied as a source of fecal contamination in freshwater. To investigate their potential role, Escherichia spp. isolates (n = 420) were recovered from possum gut contents and feces and were compared to those from water, soil, sediment, and periphyton samples, and from birds and other introduced mammals collected within the Mākirikiri Reserve, Dannevirke. Isolates were characterized using E. coli-specific real-time PCR targeting the uidA gene, Sanger sequencing of a partial gnd PCR product to generate a gnd sequence type (gST), and for 101 isolates, whole genome sequencing. Escherichia populations from 106 animal and environmental sample enrichments were analyzed using gnd metabarcoding. The alpha diversity of Escherichia gSTs was significantly lower in possums and animals compared with aquatic environmental samples, and some gSTs were shared between sample types, e.g., gST535 (in 85% of samples) and gST258 (71%). Forty percent of isolates gnd-typed and 75% of reads obtained by metabarcoding had gSTs shared between possums, other animals, and the environment. Core-genome single nucleotide polymorphism (SNP) analysis showed limited variation between several animal and environmental isolates (<10 SNPs). Our data show at an unprecedented scale that Escherichia clones are shared between possums, other wildlife, water, and the wider environment. These findings support the potential role of possums as contributors to fecal contamination in Aotearoa/New Zealand freshwater. Our study deepens the current knowledge of Escherichia populations in under-sampled wildlife. It presents a successful application of high-resolution genomic methods for fecal source tracking, thereby broadening the analytical toolbox available to water quality managers. Phylogenetic analysis of isolates and profiling of Escherichia populations provided useful information on the source(s) of fecal contamination and suggest that comprehensive invasive species management strategies may assist in restoring not only ecosystem health but also water health where microbial water quality is compromised