Linking biodiversity with environmental drivers and pressures in Great Britain

This thesis describes the original and significant development of a hierarchical statistical framework in order to realign fine-scale spatial covariate data. An example of the utilisation of this framework is given within the context of biodiversity modelling. Biodiversity is of utmost importance to the correct functioning of ecosystems and the provision of services vital to humanity. Understanding of the impacts on biodiversity by environmental drivers and pressures can help appropriate responses to be taken, to mitigate, halt or reverse damage to habitats. Therefore, linking biodiversity measures with explanatory covariates in statistical models can help understand these relationships and the extent to which certain drivers and pressures are responsible for environmental change. When modelling biodiversity, the scale at which the variables are measured should be considered. Where data are measured at different scales, a situation of misalignment arises. Misaligned data may be subject to measurement error, which can influence the resultant model, if the data are not realigned. In order to realign covariate data, two transformation approaches can be implemented. The first method is to aggregate the response data to the level of the explanatory covariates. The second method is to downscale the covariate data to the response locations. This realignment process is more complex than aggregation of the response, since it requires the uncertainty estimation of the downscaled covariate predictions. The developed framework has possible further applications in fine-scale uncertainty estimation of model covariates, where the scale at which the covariates are given is coarser than that at which the response data are available. Chapter 1 provides an introduction to the main issues and challenges in the thesis: biodiversity, data measurement, modelling techniques, scale and data realignment. The three case studies used in the development of the hierarchical framework are also introduced. Data from Loch Leven on underwater plants are analysed in chapter 2. Carabid data from ten rural locations are considered in chapter 3. In the final case study in chapter 4, coverage abundance data from sites the Countryside Survey across Great Britain are modelled. In chapter 5 the data from chapter 4 are used as the impetus; a hierarchical framework for realigning covariate data is developed and a simulation is created in order to assess its performance relative to the non-realigned model. Chapter 6 provides a summary of the case studies as well as discussion of the main issues and proposals for additional development

Collective Animal Behavior from Bayesian Estimation and Probability Matching

Animals living in groups make movement decisions that depend, among other factors, on social interactions with other group members. Our present understanding of social rules in animal collectives is based on empirical fits to observations and we lack first-principles approaches that allow their derivation. Here we show that patterns of collective decisions can be derived from the basic ability of animals to make probabilistic estimations in the presence of uncertainty. We build a decision-making model with two stages: Bayesian estimation and probabilistic matching.
In the first stage, each animal makes a Bayesian estimation of which behavior is best to perform taking into account personal information about the environment and social information collected by observing the behaviors of other animals. In the probability matching stage, each animal chooses a behavior with a probability given by the Bayesian estimation that this behavior is the most appropriate one. This model derives very simple rules of interaction in animal collectives that depend only on two types of reliability parameters, one that each animal assigns to the other animals and another given by the quality of the non-social information. We test our model by obtaining theoretically a rich set of observed collective patterns of decisions in three-spined sticklebacks, Gasterosteus aculeatus, a shoaling fish species. The quantitative link shown between probabilistic estimation and collective rules of behavior allows a better contact with other fields such as foraging, mate selection, neurobiology and psychology, and gives predictions for experiments directly testing the relationship between estimation and collective behavior

One, two, three: portable sample size in agricultural research

Determination of sample size (the number of replications) is a key step in the design of an observational study or randomized experiment. Statistical procedures for this purpose are readily available. Their treatment in textbooks is often somewhat marginal, however, and frequently the focus is on just one particular method of inference (significance test, confidence interval). Here, we provide a unified review of approaches and explain their close interrelationships, emphasizing that all approaches rely on the standard error of the quantity of interest, most often a pairwise difference of two means. The focus is on methods that are easy to compute, even without a computer. Our main recommendation based on standard errors is summarized as what we call the 1-2-3 rule for a difference of two treatment means

Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators

BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) medication is the greatest patient-enabled predictor of treatment success and mortality for those who have access to drugs. We systematically reviewed the literature to determine patient-reported barriers and facilitators to adhering to antiretroviral therapy. METHODS AND FINDINGS: We examined both developed and developing nations. We searched the following databases: AMED (inception to June 2005), Campbell Collaboration (inception to June 2005), CinAhl (inception to June 2005), Cochrane Library (inception to June 2005), Embase (inception to June 2005), ERIC (inception to June 2005), MedLine (inception to June 2005), and NHS EED (inception to June 2005). We retrieved studies conducted in both developed and developing nation settings that examined barriers and facilitators addressing adherence. Both qualitative and quantitative studies were included. We independently, in duplicate, extracted data reported in qualitative studies addressing adherence. We then examined all quantitative studies addressing barriers and facilitators noted from the qualitative studies. In order to place the findings of the qualitative studies in a generalizable context, we meta-analyzed the surveys to determine a best estimate of the overall prevalence of issues. We included 37 qualitative studies and 47 studies using a quantitative methodology (surveys). Seventy-two studies (35 qualitative) were conducted in developed nations, while the remaining 12 (two qualitative) were conducted in developing nations. Important barriers reported in both economic settings included fear of disclosure, concomitant substance abuse, forgetfulness, suspicions of treatment, regimens that are too complicated, number of pills required, decreased quality of life, work and family responsibilities, falling asleep, and access to medication. Important facilitators reported by patients in developed nation settings included having a sense of self-worth, seeing positive effects of antiretrovirals, accepting their seropositivity, understanding the need for strict adherence, making use of reminder tools, and having a simple regimen. Among 37 separate meta-analyses examining the generalizability of these findings, we found large heterogeneity. CONCLUSIONS: We found that important barriers to adherence are consistent across multiple settings and countries. Research is urgently needed to determine patient-important factors for adherence in developing world settings. Clinicians should use this information to engage in open discussion with patients to promote adherence and identify barriers and facilitators within their own populations

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction

Introduction Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups

National prospective cohort study of the burden of acute small bowel obstruction

Background Small bowel obstruction is a common surgical emergency, and is associated with high levels of morbidity and mortality across the world. The literature provides little information on the conservatively managed group. The aim of this study was to describe the burden of small bowel obstruction in the UK. Methods This prospective cohort study was conducted in 131 acute hospitals in the UK between January and April 2017, delivered by trainee research collaboratives. Adult patients with a diagnosis of mechanical small bowel obstruction were included. The primary outcome was in‐hospital mortality. Secondary outcomes included complications, unplanned intensive care admission and readmission within 30 days of discharge. Practice measures, including use of radiological investigations, water soluble contrast, operative and nutritional interventions, were collected. Results Of 2341 patients identified, 693 (29·6 per cent) underwent immediate surgery (within 24 h of admission), 500 (21·4 per cent) had delayed surgery after initial conservative management, and 1148 (49·0 per cent) were managed non‐operatively. The mortality rate was 6·6 per cent (6·4 per cent for non‐operative management, 6·8 per cent for immediate surgery, 6·8 per cent for delayed surgery; P = 0·911). The major complication rate was 14·4 per cent overall, affecting 19·0 per cent in the immediate surgery, 23·6 per cent in the delayed surgery and 7·7 per cent in the non‐operative management groups (P < 0·001). Cox regression found hernia or malignant aetiology and malnutrition to be associated with higher rates of death. Malignant aetiology, operative intervention, acute kidney injury and malnutrition were associated with increased risk of major complication. Conclusion Small bowel obstruction represents a significant healthcare burden. Patient‐level factors such as timing of surgery, acute kidney injury and nutritional status are factors that might be modified to improve outcomes

ADVISES Project: Scenario-based Requirements Analysis for e-Science Applications

We describe the requirements analysis method for e-Science which is being developed in the ADVISES project. The procedure and techniques of the method are illustrated by application to two cases studies in epidemiological bio-health informatics. Lessons learned in applying the scenario based analysis method which also embeds Human Computer Interaction principles for design and sub language analysis are discussed, in the context of data intensive e-Science research where exploratory data analysis complements more traditional hypotheses driven experimental research. 1

Midazolam does not inhibit association formation, just its storage and strengthening

Rationale Although there have been many studies examining the effects of benzodiazepines on memory performance, their effects on working memory are equivocal and little is known about whether they affect the efficacy of practice of already learned material. Objectives The objectives in two experiments were to examine (a) whether midazolam impairs performance on a working memory task designed to minimize mnemonic strategies such as rehearsal or chunking of information to be recalled and (b) the effect of midazolam on repeated practice of paired associates that were learned before drug administration. Materials and methods Both experiments involved subcutaneous administration of 0.03 mg of saline or midazolam per kilogram of bodyweight in within-subject, placebo-controlled designs, involving 23 subjects in (a) and 31 in (b). Results The drug had no effect on the ability to recall the digits in serial order even though the encoding task prevented the digits from being rehearsed or maintained in an articulatory buffer. Paired associates that were learned before the injection showed a benefit of subsequent practice under saline but not under midazolam. Conclusions The results suggest that (a) midazolam does not affect the formation of new associations in short-term memory provided that the presentation rate is not too fast to form these associations when sedated, despite the evidence that the drug blocks long-term memory (LTM) retention of associations; and (b) the potential for over-learning with practice of learned associations in LTM is adversely affected by midazolam such that repeated exposures do not strengthen new learning.</p