Characterisation of silicon carbide CMOS devices for high temperature applications

PhD ThesisIn recent years it has become increasingly apparent that there is a large demand for resilient electronics that can operate within environments that standard silicon electronics cease to function such as high power and high voltage applications, high temperatures, corrosive atmospheres and environments exposed to radiation. This has become even more essential due to increased demands for sustainable energy production and the reduction in carbon emissions worldwide, which has put a large burden on a wide range of industrial sectors who now have a significant demand for electronics to meet these needs including; military, space, aerospace, automotive, energy and nuclear. In extreme environments, where ambient temperatures may well exceed the physical limit of silicon-based technologies, SiC based technology offers a lower cost and a smaller footprint solution for operation in such environments due to its advantageous electrical properties such as a high breakdown electric field, high thermal conductivity and large saturation velocity. High quality material on large area wafers (150 mm) is now commercially available, allowing the fabrication of reliable high temperature, high frequency and high current power electronic devices, improving the already optimised silicon based structures. An important advantage of SiC is that it is the only wide band gap compound semiconductor that can be thermally oxidised to grow insulating, high quality SiO2 layers, which makes it an ideal candidate to replace silicon technologies for metal-oxide-semiconductor applications, which is the main focus of this research. Although the technology has made a number of major steps forward over recent years and the commercial manufacturing process has advanced significantly, there still remains a number of issues that need to be overcome in order to fully realise the potential of the material for electronic applications. This thesis describes the characterisation of 4H-SiC CMOS structures that were designed for high temperature applications and fabricated with varying gate dielectric treatments and process steps. The influence of process techniques on the characteristics of metal-oxide-semiconductor (MOS) devices has been investigated by means of electrical characterisation and the results have been compared to theoretical models. The C-V and I-V characteristics of both MOS capacitor and MOSFET structures with varying gate dielectrics on both n-type and p-type 4H-SiC have been analysed to explore the benefits of the varying process techniques that have been employed in the design of the devices. The results show that the field effect mobility characteristic of 4H-SiC MOSFETs are dominated at low perpendicular electric fields by Coulomb scattering and at high electric fields by low surface roughness mobility, which is due to the rough SiC-SiO2 interface. The findings also show that a thermally grown SiO2 layer at the semiconductor-dielectric interface is a beneficial process step that enhances the interfacial characteristics and increases the channel mobility of the MOSFETs. In addition to this it is also found that this technique provides the most beneficial characteristics on both n-type and p-type 4H-SiC, which suggests that it would be the most suitable treatment for a monolithic CMOS process. The impact of threshold voltage adjust ion implantation on both the MIS capacitor and MOSFET structures is also presented and shows that the increasing doses of nitrogen that are implanted to adjust the threshold voltage act to improve the device performance by acting to modify the charge at the interface or within the gate oxide and therefore increase the field effect mobility of the studied devices.Engineering and Physical Sciences Research Council (EPSRC) and Raytheon U

Globally, functional traits are weak predictors of juvenile tree growth, and we do not know why

1. Plant functional traits, in particular specific leaf area (SLA), wood density and seed mass, are often good predictors of individual tree growth rates within communities. Individuals and species with high SLA, low wood density and small seeds tend to have faster growth rates. 2. If community-level relationships between traits and growth have general predictive value, then similar relationships should also be observed in analyses that integrate across taxa, biogeographic regions and environments. Such global consistency would imply that traits could serve as valuable proxies for the complex suite of factors that determine growth rate, and, therefore, could underpin a new generation of robust dynamic vegetation models. Alternatively, growth rates may depend more strongly on the local environment or growth-trait relationships may vary along environmental gradients. 3. We tested these alternative hypotheses using data on 27352 juvenile trees, representing 278 species from 27 sites on all forested continents, and extensive functional trait data, 38% of which were obtained at the same sites at which growth was assessed. Data on potential evapotranspiration (PET), which summarizes the joint ecological effects of temperature and precipitation, were obtained from a global data base. 4. We estimated size-standardized relative height growth rates (SGR) for all species, then related them to functional traits and PET using mixed-effect models for the fastest growing species and for all species together. 5. Both the mean and 95th percentile SGR were more strongly associated with functional traits than with PET. PET was unrelated to SGR at the global scale. SGR increased with increasing SLA and decreased with increasing wood density and seed mass, but these traits explained only 3.1% of the variation in SGR. SGR-trait relationships were consistently weak across families and biogeographic zones, and over a range of tree statures. Thus, the most widely studied functional traits in plant ecology were poor predictors of tree growth over large scales. 6. Synthesis. We conclude that these functional traits alone may be unsuitable for predicting growth of trees over broad scales. Determining the functional traits that predict vital rates under specific environmental conditions may generate more insight than a monolithic global relationship can offer.Additional co-authors: Hervé Jactel, Xuefei Li, Kaoru Kitajima, Julia Koricheva, Cristina Martínez-Garza, Christian Messier, Alain Paquette, Christopher Philipson, Daniel Piotto, Lourens Poorter, Juan M. Posada, Catherine Potvin, Kalle Rainio, Sabrina E. Russo, Mariacarmen Ruiz-Jaen, Michael Scherer-Lorenzen, Campbell O. Webb, S. Joseph Wright, Rakan A. Zahawi, and Andy Hecto

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT):Study protocol for a randomised controlled feasibility trial

Background: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The ‘Prostate Cancer: Evidence of Exercise and Nutrition Trial’ investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. Methods/design: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). Discussion: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.10 page(s

A Global Model for Iodine Speciation in the Upper Ocean

An ocean iodine cycling model is presented, which predicts upper ocean iodine speciation. The model comprises a three-layer advective and diffusive ocean circulation model of the upper ocean and an iodine cycling model embedded within this circulation. The two primary reservoirs of iodine are represented, iodide and iodate. Iodate is reduced to iodide in the mixed layer in association with primary production, linked by an iodine to carbon (I:C) ratio. A satisfactory model fit with observations cannot be obtained with a globally constant I:C ratio, and the best fit is obtained when the I:C ratio is dependent on sea surface temperature, increasing at low temperatures. Comparisons with observed iodide distributions show that the best model fit is obtained when oxidation of iodide back to iodate is associated with mixed layer nitrification. Sensitivity tests, where model parameters and processes are perturbed, reveal that primary productivity, mixed layer depth, oxidation, advection, surface freshwater flux, and the I:C ratio all have a role in determining surface iodide concentrations, and the timescale of iodide in the mixed layer is sufficiently long for nonlocal processes to be important. Comparisons of the modeled iodide surface field with parameterizations by other authors show good agreement in regions where observations exist but significant differences in regions without observations. This raises the question of whether the existing parameterizations are capturing the full range of processes involved in determining surface iodide and shows the urgent need for observations in regions where there are currently none

Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial.

BACKGROUND: Circulating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile of advanced cancer, without the need to repeat tumour biopsy. We aimed to assess the accuracy of ctDNA testing in advanced breast cancer and the ability of ctDNA testing to select patients for mutation-directed therapy. METHODS: We did an open-label, multicohort, phase 2a, platform trial of ctDNA testing in 18 UK hospitals. Participants were women (aged ≥18 years) with histologically confirmed advanced breast cancer and an Eastern Cooperative Oncology Group performance status 0-2. Patients had completed at least one previous line of treatment for advanced breast cancer or relapsed within 12 months of neoadjuvant or adjuvant chemotherapy. Patients were recruited into four parallel treatment cohorts matched to mutations identified in ctDNA: cohort A comprised patients with ESR1 mutations (treated with intramuscular extended-dose fulvestrant 500 mg); cohort B comprised patients with HER2 mutations (treated with oral neratinib 240 mg, and if oestrogen receptor-positive with intramuscular standard-dose fulvestrant); cohort C comprised patients with AKT1 mutations and oestrogen receptor-positive cancer (treated with oral capivasertib 400 mg plus intramuscular standard-dose fulvestrant); and cohort D comprised patients with AKT1 mutations and oestrogen receptor-negative cancer or PTEN mutation (treated with oral capivasertib 480 mg). Each cohort had a primary endpoint of confirmed objective response rate. For cohort A, 13 or more responses among 78 evaluable patients were required to infer activity and three or more among 16 were required for cohorts B, C, and D. Recruitment to all cohorts is complete and long-term follow-up is ongoing. This trial is registered with ClinicalTrials.gov, NCT03182634; the European Clinical Trials database, EudraCT2015-003735-36; and the ISRCTN registry, ISRCTN16945804. FINDINGS: Between Dec 21, 2016, and April 26, 2019, 1051 patients registered for the study, with ctDNA results available for 1034 patients. Agreement between ctDNA digital PCR and targeted sequencing was 96-99% (n=800, kappa 0·89-0·93). Sensitivity of digital PCR ctDNA testing for mutations identified in tissue sequencing was 93% (95% CI 83-98) overall and 98% (87-100) with contemporaneous biopsies. In all cohorts, combined median follow-up was 14·4 months (IQR 7·0-23·7). Cohorts B and C met or exceeded the target number of responses, with five (25% [95% CI 9-49]) of 20 patients in cohort B and four (22% [6-48]) of 18 patients in cohort C having a response. Cohorts A and D did not reach the target number of responses, with six (8% [95% CI 3-17]) of 74 in cohort A and two (11% [1-33]) of 19 patients in cohort D having a response. The most common grade 3-4 adverse events were raised gamma-glutamyltransferase (13 [16%] of 80 patients; cohort A); diarrhoea (four [25%] of 20; cohort B); fatigue (four [22%] of 18; cohort C); and rash (five [26%] of 19; cohort D). 17 serious adverse reactions occurred in 11 patients, and there was one treatment-related death caused by grade 4 dyspnoea (in cohort C). INTERPRETATION: ctDNA testing offers accurate, rapid genotyping that enables the selection of mutation-directed therapies for patients with breast cancer, with sufficient clinical validity for adoption into routine clinical practice. Our results demonstrate clinically relevant activity of targeted therapies against rare HER2 and AKT1 mutations, confirming these mutations could be targetable for breast cancer treatment. FUNDING: Cancer Research UK, AstraZeneca, and Puma Biotechnology

The importance of different frailty domains in a population based sample in England

Background: The aim was to estimate the prevalence of frailty and relative contribution of physical/balance, nutritive, cognitive and sensory frailty to important adverse health states (falls, physical activity levels, outdoor mobility, problems in self-care or usual activities, and lack of energy or accomplishment) in an English cohort by age and sex. Methods: Analysis of baseline data from a cohort of 9803 community-dwelling participants in a clinical trial. The sample was drawn from a random selection of all people aged 70 or more registered with 63 general practices across England. Data were collected by postal questionnaire. Frailty was measured with the Strawbridge questionnaire. We used cross sectional, multivariate logistic regression to estimate the association between frailty domains and known correlates and adjusted for age. Some models were stratified by sex. Results: Mean age of participants was 78 years (sd 5.7), range 70 to 101 and 47.5% (4653/9803) were men. The prevalence of overall frailty was 20.7% (2005/9671) and there was no difference in prevalence by sex (Odds Ratio 0.98; 95% Confidence Interval 0.89 to 1.08). Sensory frailty was the most common and this was reported by more men (1823/4586) than women (1469/5056; Odds Ratio for sensory frailty 0.62, 95% Confidence Interval 0.57 to 0.68). Men were less likely than women to have physical or nutritive frailty. Physical frailty had the strongest independent associations with adverse health states. However, sensory frailty was independently associated with falls, less frequent walking, problems in self-care and usual activities, lack of energy and accomplishment. Conclusions: Physical frailty was more strongly associated with adverse health states, but sensory frailty was much more common. The health gain from intervention for sensory frailty in England is likely to be substantial, particularly for older men. Sensory frailty should be explored further as an important target of intervention to improve health outcomes for older people both at clinical and population level.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.08/14/41/DH_/Department of Health/United Kingdom Project number 08/14/41/Health Technology Assessment Programmepre-print, post-print, publisher's version/PD

Marine iodine emissions in a changing world

Iodine is a critical trace element involved in many diverse and important processes in the Earth system. The importance of iodine for human health has been known for over a century, with low iodine in the diet being linked to goitre, cretinism and neonatal death. Research over the last few decades has shown that iodine has significant impacts on tropospheric photochemistry, ultimately impacting climate by reducing the radiative forcing of ozone (O 3) and air quality by reducing extreme O 3 concentrations in polluted regions. Iodine is naturally present in the ocean, predominantly as aqueous iodide and iodate. The rapid reaction of sea-surface iodide with O 3 is believed to be the largest single source of gaseous iodine to the atmosphere. Due to increased anthropogenic O 3, this release of iodine is believed to have increased dramatically over the twentieth century, by as much as a factor of 3. Uncertainties in the marine iodine distribution and global cycle are, however, major constraints in the effective prediction of how the emissions of iodine and its biogeochemical cycle may change in the future or have changed in the past. Here, we present a synthesis of recent results by our team and others which bring a fresh perspective to understanding the global iodine biogeochemical cycle. In particular, we suggest that future climate-induced oceanographic changes could result in a significant change in aqueous iodide concentrations in the surface ocean, with implications for atmospheric air quality and climate

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy