A case of large bowel obstruction secondary to twin pregnancy

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Long-term follow-up of patients undergoing resection of tnm stage i colorectal cancer: an analysis of tumour and host determinants of outcome

Background Screening for colorectal cancer improves cancer-specific survival (CSS) through the detection of early-stage disease; however, its impact on overall survival (OS) is unclear. The present study examined tumour and host determinants of outcome in TNM Stage I disease. Methods All patients with pathologically confirmed TNM Stage I disease across 4 hospitals in the North of Glasgow between 2000 and 2008 were included. The preoperative modified Glasgow Prognostic Score (mGPS) was used as a marker of the host systemic inflammatory response (SIR). Results There were 191 patients identified, 105 (55 %) were males, 91 (48 %) were over the age of 75 years and 7 (4 %) patients underwent an emergency operation. In those with a preoperative CRP result (n = 150), 35 (24 %) patients had evidence of an elevated mGPS. Median follow-up of survivors was 116 months (minimum 72 months) during which 88 (46 %) patients died; 7 (8 %) had postoperative deaths, 15 (17 %) had cancer-related deaths and 66 (75 %) had non-cancer-related deaths. 5-year CSS was 95 % and OS was 76 %. On univariate analysis, advancing age (p < 0.001), emergency presentation (p = 0.008), and an elevated mGPS (p = 0.012) were associated with reduced OS. On multivariate analysis, only age (HR = 3.611, 95 % CI 2.049–6.365, p < 0.001) and the presence of an elevated mGPS (HR = 2.173, 95 % CI 1.204–3.921, p = 0.010) retained significance. Conclusions In patients undergoing resection for TNM Stage I colorectal cancer, an elevated mGPS was an objective independent marker of poorer OS. These patients may benefit from a targeted intervention

Augmenting NF-kappaB in poor-risk CLL: A general paradigm for other cancers?

Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder of B lymphocytes. It has an extremely variable clinical course. Some patients have a rather indolent course, whereas others are known to have a rapidly progressive disease. Most patients die from causes related to CLL that can be due to bone marrow failure, infection, or transformation to a high-grade lymphoma. Clinical stratification of CLL has revealed that a subset of patients with poor prognosis harbor cytogenetic alterations and lack mutations at the immunoglobulin locus. Therefore, the development of additional molecular biomarkers for patients at high risk for early lethality from CLL could help direct their care toward enrollment in clinical trials of promising experimental approaches such as inhibitors of BCL2 or BCR signaling or CD19 chimeric antigen receptor T cells (which have been shown to eradicate CLL in patients who have failed other approaches). In this issue, Mansouri et al. report that somatic mutations in the NFKBIE gene occur in 7% of poor prognosis patients, and this may be a common mechanism contributing to disease progression by sustaining the survival of malignant CLL cells

Factors associated with the efficacy of polyp detection during routine flexible sigmoidoscopy

Objective: Flexible sigmoidoscopy reduces the incidence of colonic cancer through the detection and removal of premalignant adenomas. However, the efficacy of the procedure is variable. The aim of the present study was to examine factors associated with the efficacy of detecting polyps during flexible sigmoidoscopy. Design and patients: Retrospective observational cohort study of all individuals undergoing routine flexible sigmoidoscopy in NHS Greater Glasgow and Clyde from January 2013 to January 2016. Results: A total of 7713 patients were included. Median age was 52 years and 50% were male. Polyps were detected in 1172 (13%) patients. On multivariate analysis, increasing age (OR 1.020 (1.016–1.023) p<0.001), male sex (OR 1.23 (1.10–1.38) p<0.001) and the use of any bowel preparation (OR 3.55 (1.47–8.57) p<0.001) were associated with increasing numbers of polyps being detected. There was no significant difference in the number of polyps found in patients who had received an oral laxative preparation compared with an enema (OR 3.81 (1.57–9.22) vs 3.45 (1.43–8.34)), or in those who received sedation versus those who had not (OR 1.00 vs 1.04 (0.91–1.17) p=0.591). Furthermore, the highest number of polyps was found when the sigmoidoscope was inserted to the descending colon (OR 1.30 (1.04–1.63)). Conclusions: Increasing age, male sex and the utilisation of any bowel preparation were associated with an increased polyp detection rate. However, the use of sedation or oral laxative preparation appears to confer no additional benefit. In addition, the results indicate that insertion to the descending colon optimises the efficacy of flexible sigmoidoscopy polyp detection

An investigation into the impact of screening on tumour and host determinants of outcome in colorectal cancer

Colorectal cancer is the third most common cancer and the second most common cause of cancer death in the UK. Outcome is directly related to stage at diagnosis with over 90% of patients with Stage I disease surviving their disease to 5 years compared to less than 10% of those with Stage IV disease. Symptoms for colorectal cancer can be non-specific, particularly when the disease is at its early stage, and hence screening has been introduced. Population screening in the UK, using faecal occult blood testing (FOBt) has been introduced over the past 10 years following several major randomized control trials and a Cochrane review that has shown improved cancer specific mortality in the region of 15% in those individuals invited. This has been attributed to the detection of early stage disease with around 50% of all tumours detected through screening being Stage I. However, it has previously been shown that there are additional tumour and host prognostic factors outside of stage that can determine outcome. For example, the presence of venous invasion and the presence of an elevated host systemic inflammatory response have been associated with poorer cancer specific survival. These additional factors have not previously been studied within the context of a population screening programme or indeed within early stage disease. Moreover, the FOBt screening programme itself is not without its pitfalls. Uptake of the test is below that of other established cancer screening programmes and it is recognised that repeated screening rounds are required to achieve an acceptable sensitivity of the test. This thesis sought to examine the first round of the Scottish Bowel Screening Programme within the West of Scotland and assess its effect on tumour and host determinants of outcome. In Chapter 1 an overview of colorectal cancer and current determinants of outcome is provided. In addition, colorectal cancer screening is explored in detail including the evidence behind the current screening programme. Chapter 2 presents original data, utilising population databases, examining the changes in mode, site and stage of presentation across the West of Scotland that have accompanied the introduction of the national screening programme. It identifies that within non-metastatic disease there has been a shift towards a higher proportion of Stage I disease being present following screening introduction. Chapter 3 presents a detailed examination of the first round of screening in NHS Greater Glasgow & Clyde (NHS GG&C) emphasising the importance of the impact of deprivation throughout the screening programme. For example, deprived patients were less likely to take part, more likely to test positive, less likely to proceed to colonscopy following a positive test and less likely to have cancer detected at colonoscopy following a positive test. Chapters 4, 5 and 6 utilise an original dataset of over 4000 patients who underwent colonoscopy following a positive test in the first round of screening in NHS GG&C generated through work from Chapter 3. Firstly, in Chapter 4, a theoretical model proposing a flexible sigmoidoscopy as a first line test, rather than a colonoscopy, is examined. It found a missed cancer rate of 17% and that around a third would require a completion colonoscopy, concluding that this would not be a desirable change to the current screening algorithm. Chapter 5 then examines the importance of potentially chemopreventative medications such as statins and aspirin, on the risk of neoplasia at colonoscopy, determining that patients on such medications did indeed have lower rates of neoplasia, significant neoplasia and cancer than those not on them. Chapter 6 then looks at symptoms in this population, identifying that around 40% had at least one bowel symptom however that these correlated poorly with the risk of significant neoplasia at colonoscopy. Chapter 7 explores outcomes in those who were invited but did not have a screen-detected cancer in order to examine the incidence of interval cancers (colorectal cancer within 2 years of a negative FOBt) and cancers in non-responders. Overall it identified a 30% interval cancer rate. The chapter then explores differences in tumour and host factors between screen-detected and non screen-detected disease reporting that stage for stage, patients with non screen-detected disease had higher rates of systemic inflammation. Furthermore it characterises the similarity between interval and non-responder tumours suggesting that rather than representing biologically more aggressive tumours, interval cancers arise due to limitations of the test itself. Chapter 8 presents long-term outcomes in patients who have undergone a resection for Stage I disease prior to the introduction of screening. The results report an excellent 5-year cancer specific survival of 95% however an overall survival of 76%. It identifies the presence of an elevated pre-operative host inflammatory response as being associated with a worse overall outcome. Tissue work exploring the local immune-cell microenvironment of both early stage and pre-malignant disease is the focus for Chapters 9 and 10. This characterisation of immune cell infiltrate identifies similar rates of peritumoural inflammation between T1 and T2 disease and validates a previously published automated scoring system. When exploring local inflammation within premalignant polyps there appears to be a change from low-grade to high-grade dysplasia signifying a specific response to early disease progression suggesting host immunosurveillance. Chapter 11 summarises the main findings of the thesis and presents future directions

The Hamiltonian Cycle and Travelling Salesperson problems with traversal-dependent edge deletion

Variants of the well-known Hamiltonian Cycle and Travelling Salesperson problems have been studied for decades. Existing formulations assume either a static graph or a temporal graph in which edges are available based on some function of time. In this paper, we introduce a new variant of these problems inspired by applications such as open-pit mining, harvesting and painting, in which some edges become deleted or untraversable depending on the vertices that are visited. We formally define these problems and provide both a theoretical and experimental analysis of them in comparison with the conventional versions. We also propose two solvers, based on an exact backward search and a meta-heuristic solver, and provide an extensive experimental evaluation

Managing Vulnerabilities of Tactical Wireless RF Network Systems: A Case Study

Organisations and individuals benefit when wireless networks are protected. After assessing the risks associated with wireless technologies, organisations can reduce the risks by applying countermeasures to address specific threats and vulnerabilities. These countermeasures include management, operational and technical controls. While these countermeasures will not prevent all penetrations and adverse events, they can be effective in reducing many of the common risks associated with wireless RF networks. Among engineers dealing with different scaled and interconnected engineering systems, such as tactical wireless RF communication systems, there is a growing need for a means of analysing complex adaptive systems. We propose a methodology based on the systematic resolution of complex issues to manage the vulnerabilities of tactical wireless RF systems. There are is a need to assemble and balance the results of any successful measure, showing how well each solution meets the system’s objectives. The uncertain arguments used and other test results are combined using a form of mathematical theory for their analysis. Systems engineering thinking supports design decisions and enables decision‐makers to manage and assess the support for each solution. In these circumstances, complexity management arises from the many interacting and conflicting requirements of an increasing range of possible parameters. There may not be a single ‘right’ solution, only a satisfactory set of resolutions which this system helps to facilitate. Smart and innovative performance matrixes are introduced using a mathematical Bayesian network to manage, model, calculate and analyse all the potential vulnerability paths in wireless RF networks

Mental healthcare in Kenya:exploring optimal conditions for capacity building

The global burden of disease related to mental disorders is on the increase, with the World Health Organization (WHO) estimating that over 450 million people are affected worldwide. The Mental Health Global Action Program (mhGAP) was launched by the WHO in 2002 in order to address the widening gap in access to mental healthcare in low-income countries. Despite these efforts, access to mental healthcare in low-income countries remains poor and is often described as inadequate, inefficient and inequitable, with an 85% estimated treatment gap in low-income countries, as compared with 35% to 50% in high-income countries.In this article, the authors argue that integrating mental health services into primary healthcare settings through capacity building is vital with regard to achieving mhGAP goals. The article explores the challenges to and potential enablers for the improvement of the delivery of broad-based mental healthcare services in Kenya. The authors propose the integration of the conceptual dimensions of both the cosmopolitanism and capabilities approaches as a combined strategy for dealing with capacity building in heterogeneous settings such as Kenya

Distributed System Contract Monitoring

The use of behavioural contracts, to specify, regulate and verify systems, is particularly relevant to runtime monitoring of distributed systems. System distribution poses major challenges to contract monitoring, from monitoring-induced information leaks to computation load balancing, communication overheads and fault-tolerance. We present mDPi, a location-aware process calculus, for reasoning about monitoring of distributed systems. We define a family of Labelled Transition Systems for this calculus, which allow formal reasoning about different monitoring strategies at different levels of abstractions. We also illustrate the expressivity of the calculus by showing how contracts in a simple contract language can be synthesised into different mDPi monitors.Comment: In Proceedings FLACOS 2011, arXiv:1109.239