An account of epistemic democracy: ignorant majorities and the better decision

This thesis analyses traditional and contemporary democratic theory from an epistemic, instrumental angle. It argues that these theories depend too heavily on intrinsic values, such as equality of participation, which then sacrifice good decision outcomes. Using a reverse-contractarian tool, where social contracts can be prospective rather than retrospective, it is possible to argue that a free public would form government on the basis of services it provides and ergo, instrumental reasons. As such, legitimate decisions are those that are based upon an evidential diagnosis of a problem, and use evidence to help bring about the good provision of such problem-solving services. It uses the observation of topic-specific ignorant majorities, defined as being where each citizen has both areas of expertise and areas of ignorance, to criticise both fair-proceduralist accounts and non-democratic technocratic accounts. The former overstates the contribution that every citizen can have when designing and managing those services, whereas the latter understates the broader contribution knowledgeable minorities can have in governance. Overall, a tailored democracy is called for using the name service democracy, which is a theoretical response to the above observations. It concludes by offering epistemic policy proposals that could be implemented within the current governmental institutions and policy processes. It calls for state-funding of political parties to avoid undue influence over policy, committee oversight of ministerial appointments so that competence can be assessed and finally academic and professional crowd-sourcing to allow the wider knowledgeable minority in a given area to contribute to policy creation and development

An account of epistemic democracy: ignorant majorities and the better decision

This thesis analyses traditional and contemporary democratic theory from an epistemic, instrumental angle. It argues that these theories depend too heavily on intrinsic values, such as equality of participation, which then sacrifice good decision outcomes. Using a reverse-contractarian tool, where social contracts can be prospective rather than retrospective, it is possible to argue that a free public would form government on the basis of services it provides and ergo, instrumental reasons. As such, legitimate decisions are those that are based upon an evidential diagnosis of a problem, and use evidence to help bring about the good provision of such problem-solving services. It uses the observation of topic-specific ignorant majorities, defined as being where each citizen has both areas of expertise and areas of ignorance, to criticise both fair-proceduralist accounts and non-democratic technocratic accounts. The former overstates the contribution that every citizen can have when designing and managing those services, whereas the latter understates the broader contribution knowledgeable minorities can have in governance. Overall, a tailored democracy is called for using the name service democracy, which is a theoretical response to the above observations. It concludes by offering epistemic policy proposals that could be implemented within the current governmental institutions and policy processes. It calls for state-funding of political parties to avoid undue influence over policy, committee oversight of ministerial appointments so that competence can be assessed and finally academic and professional crowd-sourcing to allow the wider knowledgeable minority in a given area to contribute to policy creation and development

Radiotherapy for Soft Tissue Sarcoma of the Proximal Lower Extremity

Soft-tissue sarcoma (STS) is a histopathologically diverse group of tumors accounting for approximately 10,000 new malignancies in the US each year. The proximal lower extremity is the most common site for STS, accounting for approximately one-third of all cases. Coordinated multimodality management in the form of surgery and radiation is often critical to local control, limb preservation, and functional outcome. Based on a review of currently available Medline literature and professional experience, this paper provides an overview of the treatment of STS of the lower extremity with a particular focus on the modern role of radiotherapy

Parallelized Hybrid Monte Carlo Simulation of Stress-Induced Texture Evolution

A parallelized hybrid Monte Carlo (HMC) methodology is devised to quantify the microstructural evolution of polycrystalline material under elastic loading. The approach combines a time explicit material point method (MPM) for the mechanical stresses with a calibrated Monte Carlo (cMC) model for grain boundary kinetics. The computed elastic stress generates an additional driving force for grain boundary migration. The paradigm is developed, tested, and subsequently used to quantify the effect of elastic stress on the evolution of texture in nickel polycrystals. As expected, elastic loading favors grains which appear softer with respect to the loading direction. The rate of texture evolution is also quantified, and an internal variable rate equation is constructed which predicts the time evolution of the distribution of orientations.Comment: 20 pages, 8 figure

Molecular signatures of differential responses to exercise trainings during rehabilitation.

The loss and recovery of muscle mass and function following injury and during rehabilitation varies among individuals. While recent expression profiling studies have illustrated transcriptomic responses to muscle disuse and remodeling, how these changes contribute to the physiological responses are not clear. In this study, we quantified the effects of immobilization and subsequent rehabilitation training on muscle size and identified molecular pathways associated with muscle responsiveness in an orthopaedic patient cohort study. The injured leg of 16 individuals with ankle injury was immobilized for a minimum of 4 weeks, followed by a 6-week rehabilitation program. The maximal cross-sectional area (CSA) of the medial gastrocnemius muscle of the immobilized and control legs were determined by T1-weighted axial MRI images. Genome-wide mRNA profiling data were used to identify molecular signatures that distinguish the patients who responded to immobilization and rehabilitation and those who were considered minimal responders. RESULTS: Using 6% change as the threshold to define responsiveness, a greater degree of changes in muscle size was noted in high responders (−14.9 ± 3.6%) compared to low responders (0.1 ± 0.0%) during immobilization. In addition, a greater degree of changes in muscle size was observed in high responders (20.5 ± 3.2%) compared to low responders (2.5 ± 0.9%) at 6-week rehabilitation. Microarray analysis showed a higher number of genes differentially expressed in the responders compared to low responders in general; with more expression changes observed at the acute stage of rehabilitation in both groups. Pathways analysis revealed top molecular pathways differentially affected in the groups, including genes involved in mitochondrial function, protein turn over, integrin signaling and inflammation. This study confirmed the extent of muscle atrophy due to immobilization and recovery by exercise training is associated with distinct remodeling signature, which can potentially be used for evaluating and predicting clinical outcomes

How different data sources and definitions of neighbourhood influence the association between food outlet availability and body mass index: a cross-sectional study.

Inconsistencies in methodologies continue to inhibit understanding of the impact of the environment on body mass index (BMI). To estimate the effect of these differences, we assessed the impact of using different definitions of neighbourhood and data sets on associations between food outlet availability within the environment and BMI. Previous research has not extended this to show any differences in the strength of associations between food outlet availability and BMI across both different definitions of neighbourhood and data sets. Descriptive statistics showed differences in the number of food outlets, particularly other food retail outlets between different data sets and definitions of neighbourhood. Despite these differences, our key finding was that across both different definitions of neighbourhood and data sets, there was very little difference in size of associations between food outlets and BMI. Researchers should consider and transparently report the impact of methodological choices such as the definition of neighbourhood and acknowledge any differences in associations between the food environment and BMI

A pilot randomised controlled trial of personalised care for depressed patients with symptomatic coronary heart disease in South London general practices: the UPBEAT-UK RCT protocol and recruitment.

ABSTRACT: Background: Community studies reveal people with coronary heart disease (CHD) are twice as likely to be depressed as the general population and that this co-morbidity negatively affects the course and outcome of both conditions. There is evidence for the efficacy of collaborative care and case management for depression treatment, and whilst NICE guidelines recommend these approaches only where depression has not responded to psychological, pharmacological, or combined treatments, these care approaches may be particularly relevant to the needs of people with CHD and depression in the earlier stages of stepped care in primary care settings. Methods: This pilot randomised controlled trial will evaluate whether a simple intervention involving a personalised care plan, elements of case management and regular telephone review is a feasible and acceptable intervention that leads to better mental and physical health outcomes for these patients. The comparator group will be usual general practitioner (GP) care. 81 participants have been recruited from CHD registers of 15 South London general practices. Eligible participants have probable major depression identified by a score of ≥8 on the Hospital Anxiety and Depression Scale depression subscale (HADS-D) together with symptomatic CHD identified using the Modified Rose Angina Questionnaire. Consenting participants are randomly allocated to usual care or the personalised care intervention which involves a comprehensive assessment of each participant’s physical and mental health needs which are documented in a care plan, followed by regular telephone reviews by the case manager over a 6-month period. At each review, the intervention participant’s mood, function and identified problems are reviewed and the case manager uses evidence based behaviour change techniques to facilitate achievement of goals specified by the patient with the aim of increasing the patient’s self efficacy to solve their problems. Depressive symptoms measured by HADS score will be collected at baseline and 1, 6- and 12 months post randomisation. Other outcomes include CHD symptoms, quality of life, wellbeing and health service utilisation. Discussion: This practical and patient-focused intervention is potentially an effective and accessible approach to the health and social care needs of people with depression and CHD in primary care. Trial registration: ISRCTN21615909

Progress Toward a Human CD4/CCR5 Transgenic Rat Model for De Novo Infection by Human Immunodeficiency Virus Type 1

The development of a permissive small animal model for the study of human immunodeficiency virus type (HIV)-1 pathogenesis and the testing of antiviral strategies has been hampered by the inability of HIV-1 to infect primary rodent cells productively. In this study, we explored transgenic rats expressing the HIV-1 receptor complex as a susceptible host. Rats transgenic for human CD4 (hCD4) and the human chemokine receptor CCR5 (hCCR5) were generated that express the transgenes in CD4+ T lymphocytes, macrophages, and microglia. In ex vivo cultures, CD4+ T lymphocytes, macrophages, and microglia from hCD4/hCCR5 transgenic rats were highly susceptible to infection by HIV-1 R5 viruses leading to expression of abundant levels of early HIV-1 gene products comparable to those found in human reference cultures. Primary rat macrophages and microglia, but not lymphocytes, from double-transgenic rats could be productively infected by various recombinant and primary R5 strains of HIV-1. Moreover, after systemic challenge with HIV-1, lymphatic organs from hCD4/hCCR5 transgenic rats contained episomal 2–long terminal repeat (LTR) circles, integrated provirus, and early viral gene products, demonstrating susceptibility to HIV-1 in vivo. Transgenic rats also displayed a low-level plasma viremia early in infection. Thus, transgenic rats expressing the appropriate human receptor complex are promising candidates for a small animal model of HIV-1 infection

Estimating the Cost-Effectiveness of Implementation : Is Sufficient Evidence Available?

BACKGROUND: Timely implementation of recommended interventions can provide health benefits to patients and cost savings to the health service provider. Effective approaches to increase the implementation of guidance are needed. Since investment in activities that improve implementation competes for funding against other health generating interventions, it should be assessed in term of its costs and benefits. OBJECTIVE: In 2010, the National Institute for Health and Care Excellence released a clinical guideline recommending natriuretic peptide (NP) testing in patients with suspected heart failure. However, its implementation in practice was variable across the National Health Service in England. This study demonstrates the use of multi-period analysis together with diffusion curves to estimate the value of investing in implementation activities to increase uptake of NP testing. METHODS: Diffusion curves were estimated based on historic data to produce predictions of future utilization. The value of an implementation activity (given its expected costs and effectiveness) was estimated. Both a static population and a multi-period analysis were undertaken. RESULTS: The value of implementation interventions encouraging the utilization of NP testing is shown to decrease over time as natural diffusion occurs. Sensitivity analyses indicated that the value of the implementation activity depends on its efficacy and on the population size. CONCLUSIONS: Value of implementation can help inform policy decisions of how to invest in implementation activities even in situations in which data are sparse. Multi-period analysis is essential to accurately quantify the time profile of the value of implementation given the natural diffusion of the intervention and the incidence of the disease