Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Stochastic agent-based modelling for reality

This D.Phil. thesis develops a new agent-based simulation model to improve the results of analysis, which solely uses discrete choice modelling, as well as to analyse the effects of a road user charging scheme for the Upper Derwent Valley in the Peak District National Park. The advantages of discrete choice analysis are well known. However, results with these conventional conventional approaches, which conduct analysis solely with discrete choice models, can be biased if interaction and learning effects are significant. The Minority Game, in which agents try to choose the option of the minority side, is an appropriate tool to deal with these problems. The situation in the Upper Derwent Valley can be explained with economic game theories and the Minority Game. The two approaches mutually help to analyse the situation in the Upper Derwent Valley leading to the development of a stochastic Minority Game. The stochastic Minority Game was tested with an online game (questionnaire), which was played 3,886 times by response in all around the world. The practical part of this thesis examines the components of the stochastic Minority Game with the data collected around the Upper Derwent Valley. The main data was collected using a stated preference survey. Overall, 700 questionnaires were distributed and 323 of them were returned (i.e. a return rate of 46.1 %). In the practical part, the agent-based model has four sub modules: 1) Multinomial mixed logit model for mode choice, 2) Binary logit model for parking location choice, 3) Markov queue model for parking network, and 4) the Minority Game for parking congestion and learning. This simulation model produces comprehensive outputs including mode choices, congestion levels, and user utilities. The results show that the road user charging scheme reduces car demand in the Upper Derwent Valley and ensures a reduction in congestion at the parking areas. The model also shows that an exemption will increase the utilities of elderly visitors without substantially sacrificing those of younger visitors. In conclusion, the simulation model demonstrated that oversimplification in conventional approaches solely using discrete choice models gave significant biases when real world problems were analysed

Issues in the implementation of road user charging in UK national parks: the case of Upper Derwent Valley in the Peak District National Park

This paper describes how road user charging is considered as a transport management tool for various urban areas worldwide. However, rural or protected areas might also be affected by such policies. This paper focuses on the implications of the proposed road user charging scheme in an area of the Peak District National Park in the UK. By applying both qualitative and quantitative methods it highlights the importance of issues such as scheme acceptability, funding and timing of implementation of the scheme, as well as the obvious differences compared with similar schemes for urban areas

Forecasting the effects of road user charge by stochastic agent-based modelling

This paper develops a new agent-based simulation model to improve discrete choice analysis as well as to analyse the effects of a road user charging scheme for the Upper Derwent Valley in the Peak District National Park. The advantages of discrete choice analysis are well known. However, results with these conventional methods can be biased if interaction effects are significant. The combined approach of the Minority Game, in which agents try to choose the option of the minority side, and discrete choice analysis is appropriate to deal with the problem.The main data was collected by stated preference survey. The agent-based model has four sub-modules: (1) multinomial mixed logit model for mode choice, (2) binary logit model for parking location choice, (3) Markov queue model for parking network, and (4) the Minority Game for parking congestion and learning.The results show that the road user charging scheme reduces car demand in the Upper Derwent Valley. The model also shows that an exemption will increase the utility of elderly visitors. In conclusion, the simulation model demonstrated that oversimplification in conventional discrete choice analysis gave significant biases when real world problems were analysed

Stochastic agent-based modelling for reality : dynamic discrete choice analysis with interaction

This D.Phil. thesis develops a new agent-based simulation model to improve the results of analysis, which solely uses discrete choice modelling, as well as to analyse the effects of a road user charging scheme for the Upper Derwent Valley in the Peak District National Park. The advantages of discrete choice analysis are well known. However, results with these conventional conventional approaches, which conduct analysis solely with discrete choice models, can be biased if interaction and learning effects are significant. The Minority Game, in which agents try to choose the option of the minority side, is an appropriate tool to deal with these problems. The situation in the Upper Derwent Valley can be explained with economic game theories and the Minority Game. The two approaches mutually help to analyse the situation in the Upper Derwent Valley leading to the development of a stochastic Minority Game. The stochastic Minority Game was tested with an online game (questionnaire), which was played 3,886 times by response in all around the world. The practical part of this thesis examines the components of the stochastic Minority Game with the data collected around the Upper Derwent Valley. The main data was collected using a stated preference survey. Overall, 700 questionnaires were distributed and 323 of them were returned (i.e. a return rate of 46.1 %). In the practical part, the agent-based model has four sub modules: 1) Multinomial mixed logit model for mode choice, 2) Binary logit model for parking location choice, 3) Markov queue model for parking network, and 4) the Minority Game for parking congestion and learning. This simulation model produces comprehensive outputs including mode choices, congestion levels, and user utilities. The results show that the road user charging scheme reduces car demand in the Upper Derwent Valley and ensures a reduction in congestion at the parking areas. The model also shows that an exemption will increase the utilities of elderly visitors without substantially sacrificing those of younger visitors. In conclusion, the simulation model demonstrated that oversimplification in conventional approaches solely using discrete choice models gave significant biases when real world problems were analysed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

An analysis of road user charging and road pricing at the upper Derwent Valley, UK

This paper discusses the effect of the road user charging scheme at the Peak District National Park, UK. The analysis was carried out with stated preference survey techniques and using a multinomial mixed logit model as well as conventional statistic and regression models. The analysis focused on not only the congestion level and environmental impact, but also equity issues associated with the road user charging scheme. From the estimation results, the scheme has great potential to reduce congestion in this area of natural beauty. However, the potential monetary policy tool also presents an equity problem, because elderly visitors will be more willing to pay the toll and the fee to park at the Information Centre. In other words, elderly visitors are more disadvantaged than other visitors. This example shows how a monetary policy tool causes an uneven effect.</p

Role of microfinance to support agricultural climate change adaptations in Indonesia : Encouraging private sector participation in climate finance

The demands of mitigation and adaptation policies are important to understanding a country's climate change preparation by providing microfinance in the agricultural sector. This could be seen as a strategy to fight against the challenges of future food security. In 2014, Indonesia established climate change adaptation policies. This legislation aims to pave the way for making actions on climate change adaptation mainstream in national and local development planning. Public and private finance have supported the implementation of the climate actions. However, most funding is still used for mitigation. Adaptation finance needs support, especially in agriculture. This research paper studies opportunities for microfinance to play a role together with existing resources in supporting climate change adaptation in Indonesia. The data was acquired and analysed through a literature review, analysis of case studies and interviews with stakeholders in the climate change-related financial sector. The central findings regarding the opportunity for microfinance to contribute to the existing schemes in Indonesian climate change adaptation finance for agriculture are worthy of the result. This study found that adaptation finance is mostly used for indirect activities. Meanwhile, local communities, and farmers in particular, need directly targeted measures to adapt to climate change. An alternative approach is providing microfinance, insurance and capacity development for farmers to produce high quality agricultural products. This would contribute to optimizing the agri-food value chain, which supports socio-economic development of stakeholders, especially farmers. Hence, microfinance appears to be one potential solution to support direct climate change adaptation actions for the agricultural sector. However, this may not be strong enough to finance the entire needs for agricultural climate actions. Adaptation is contextual, so it has to be grounded in the needs of local communities. Microfinance needs public sectors support as well as other resources from the private sector. In the case of rapid response to disasters, which often destroy the agricultural sector, microfinance should be advantageous in supporting adaptation. However, in reality, it does not work, as it is prevented by regulations. So, this can be an area the public sector can support as a risk-taker as well as by providing initial funds and resources for scaling up efforts

Comparative Study on Agriculture and Forestry Climate Change Adaptation Projects in Mongolia, the Philippines, and Timor Leste

The impacts of climate change, such as increasing temperature, erratic rainfall pattern, sea level rise, etc., are being increasingly reported. These impacts are destructive for human activities and thus the development and improvement of mitigation and adaptation strategies is a priority globally. In the least developed and developing countries, adequate adaptive capacities are required so to boost the resilience of communities towards the projected climate change projected. Moreover, activities of climate change adaptation not only provide solutions and strategies to deal with climate change, but also encourage sustainable development. This comparative study evaluates projects in three countries: Mongolia, The Philippines, and Timor Leste, by mapping and contrasting the factors that contribute to adaptive capacity and support sustainable development. A heuristic matrix was used to articulate the capacities that influenced the desired outcomes of each project. Some key components of adaptive capacity were identified in each context. The interaction of those components improved the generic and specific capacity at individual and system level then ultimately improved resilience towards climate change