Iterative synthetic aperture radar imaging algorithms

Synthetic aperture radar is an important tool in a wide range of civilian and military imaging applications. This is primarily due to its ability to image in all weather conditions, during both the day and the night, unlike optical imaging systems. A synthetic aperture radar system contains a step which is not present in an optical imaging system, this is image formation. This is required because the acquired data from the radar sensor does not directly correspond to the image. Instead, to form an image, the system must solve an inverse problem. In conventional scenarios, this inverse problem is relatively straight forward and a matched lter based algorithm produces an image of suitable image quality. However, there are a number of interesting scenarios where this is not the case. Scenarios where standard image formation algorithms are unsuitable include systems with data undersampling, errors in the system observation model and data that is corrupted by radio frequency interference. Image formation in these scenarios will form the topics of this thesis and a number of iterative algorithms are proposed to achieve image formation. The motivation for these proposed algorithms is primarily from the eld of compressed sensing, which considers the recovery of signals with a low-dimensional structure. The rst contribution of this thesis is the development of fast algorithms for the system observation model and its adjoint. These algorithms are required by large-scale gradient based iterative algorithms for image formation. The proposed algorithms are based on existing fast back-projection algorithms, however, a new decimation strategy is proposed which is more suitable for some applications. The second contribution is the development of a framework for iterative near- eld image formation, which uses the proposed fast algorithms. It is shown that the framework can be used, in some scenarios, to improve the visual quality of images formed from fully sampled data and undersampled data, when compared to images formed using matched lter based algorithms. The third contribution concerns errors in the system observation model. Algorithms that correct these errors are commonly referred to as autofocus algorithms. It is shown that conventional autofocus algorithms, which work as a post-processor on the formed image, are unsuitable for undersampled data. Instead an autofocus algorithm is proposed which corrects errors within the iterative image formation procedure. The proposed algorithm is provably stable and convergent with a faster convergence rate than previous approaches. The nal contribution is an algorithm for ultra-wideband synthetic aperture radar image formation. Due to the large spectrum over which the ultra-wideband signal is transmitted, there is likely to be many other users operating within the same spectrum. These users can produce signi cant radio frequency interference which will corrupt the received data. The proposed algorithm uses knowledge of the RFI spectrum to minimise the e ect of the RFI on the formed image

Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis

Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and assessed clonal structure using whole-genome sequencing and amplicon resequencing of 112 EACs. We next screened a cohort of 109 biopsies from 2 key transition points in the development of malignancy: benign metaplastic never-dysplastic Barrett's esophagus (NDBE; n = 66) and high-grade dysplasia (HGD; n = 43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 mutations occurred in a stage-specific manner, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett's esophagus in a new non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies

Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma

The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett's esophagus and EAC samples, together with one in-depth Barrett's esophagus case study sampled over time and space, we have provided the following new insights: (i) Barrett's esophagus is polyclonal and highly mutated even in the absence of dysplasia; (ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett's esophagus; and (iii) despite differences in specific coding mutations, the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett's epithelium, and a molecular Cytosponge technique overcomes sampling bias and has the capacity to reflect the entire clonal architecture.</p

Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Background: Respiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity. Methods: PRISM was an open-label, randomised, phase 3 trial done at 70 hospitals across six countries. Patients aged 50 years or older who were undergoing elective major open abdominal surgery were randomly assigned (1:1) to receive CPAP within 4 h of the end of surgery or usual postoperative care. Patients were randomly assigned using a computer-generated minimisation algorithm with inbuilt concealment. The primary outcome was a composite of pneumonia, endotracheal re-intubation, or death within 30 days after randomisation, assessed in the intention-to-treat population. Safety was assessed in all patients who received CPAP. The trial is registered with the ISRCTN registry, ISRCTN56012545. Findings: Between Feb 8, 2016, and Nov 11, 2019, 4806 patients were randomly assigned (2405 to the CPAP group and 2401 to the usual care group), of whom 4793 were included in the primary analysis (2396 in the CPAP group and 2397 in the usual care group). 195 (8\ub71%) of 2396 patients in the CPAP group and 197 (8\ub72%) of 2397 patients in the usual care group met the composite primary outcome (adjusted odds ratio 1\ub701 [95% CI 0\ub781-1\ub724]; p=0\ub795). 200 (8\ub79%) of 2241 patients in the CPAP group had adverse events. The most common adverse events were claustrophobia (78 [3\ub75%] of 2241 patients), oronasal dryness (43 [1\ub79%]), excessive air leak (36 [1\ub76%]), vomiting (26 [1\ub72%]), and pain (24 [1\ub71%]). There were two serious adverse events: one patient had significant hearing loss and one patient had obstruction of their venous catheter caused by a CPAP hood, which resulted in transient haemodynamic instability. Interpretation: In this large clinical effectiveness trial, CPAP did not reduce the incidence of pneumonia, endotracheal re-intubation, or death after major abdominal surgery. Although CPAP has an important role in the treatment of respiratory failure after surgery, routine use of prophylactic post-operative CPAP is not recommended