Sensitivity Analysis of Electrocardiogram Features to Computational Model Input Parameters

Cardiac models of electrophysiology capable of generating simulated electrocardiogram (ECG) signals are an increasingly valuable tool for both personalised medicine and understanding cardiac pathologies. Sensitivity analysis (SA) can provide crucial insight into how simulation parameters affect ECG morphology. We use two SA methods, direct numerical evaluation of integrals and polynomial chaos expansion, to calculate main and total effects for ECG features extracted from QRS complexes generated by a cardiac ventricular model. The importance of stimulation site parameters on output ECG features is evaluated. SA methods can highlight and quantify important input parameters for different ECG morphology features, which in some cases can be linked to physiological explanations. For example R peak amplitude in lead II depends on apicobasal location of stimulation sites in the left ventricle. Furthermore, different SA methods have different strengths and weaknesses. Insight into parameter importance supports model development and allows for more nuanced and patient-specific simulation changes

Methods of enhancing the sustainability and scale of community based disaster risk management

Disasters are always local in their impact, and therefore approaches towards their alleviation need to be designed and implemented based on this certainty. So this research is designed to investigate methods of enhancing the development, sustainability and scale of community based disaster risk management (CBDRM). This is undertaken with a special focus upon community risk assessment (CRA) and its relationship with disaster risk reduction (DRR). Action Research (AR) is the methodological approach adopted to investigate three primary research objectives: • To investigate the link between community risk assessment (CRA) and community based disaster risk management (CBDRM). • To identify key issues when addressing the underlying causes of vulnerability within community based disaster risk management (CBDRM). • To identify challenges in enhancing the sustainability and scale of community based disaster risk management (CBDRM) through stakeholder partnership. The AR carried out has three main components: 1. The development and testing of a CRA methodology. 2. The identification of good practice CBDRM. 3. Supplementary semi-structured interviews. Perspectives on the research objectives are collated from a broad array of international experiences, but with the primary location of fieldwork in Bihar, India. Conclusions to the research demonstrate the importance of linking government policy and practice on DRR with CBDRM, and addressing the underlying causes of vulnerability. While important in their own right, these subjects have also been considered in terms of their inter-connectedness with one another. Indeed they are shown to be mutually reinforcing. However, even more pivotal is the emphasis on their relationship with CRA. Furthermore, contrary to much practice CRA, engaging government officials from the outset and incorporating an investigation into the underlying causes of vulnerability, must not be segregated from action planning but must be fully synchronised with a CBDRM process.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The contribution of ecosystem services to human resilience: a rapid review

Frameworks that link ecosystems services (ES) and human resilience are still nascent. The links between ES and human wellbeing are still not well understood, and links to resilience even less so. The debate around human resilience in itself is still ongoing in the literature. However, there has been a growth in interdisciplinary science around ES and there is growing evidence that ES support human resilience

High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial.

BACKGROUND: Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent. METHODS: We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3). This trial is registered with ClinicalTrials.gov number NCT00419068. FINDINGS: 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90-2·16; p=0.14). TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (p(interaction)=0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36-48·01; p=0·02). FokI genotype did not modify the effect of vitamin D supplementation (p(interaction)=0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6-88·2; p<0·0001). INTERPRETATION: Administration of four doses of 2·5 mg vitamin D(3) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism. FUNDING: British Lung Foundation