Comparing multiple simulators using Bayesian emulators

Bayesian emulation has proved to be a useful tool for working with complicated, high dimensional simulators, approximating the simulator's behaviour in a probabilistic way, enabling operations such as prediction or calibration, and therefore providing an ecient approximation to the simulator's representation of the system. Complex systems, however, are often modelled by several different simulators, each with dierent strengths and weaknesses. Combining them to better understand the system, or comparing their behaviour as functions, is very dicult. This is largely because their input spaces cannot be directly linked. In this thesis, we present two methods for using emulation to jointly model two simulators, allowing them to be compared. We also introduce two simulators of the ocean carbon cycle, OG99NPZD and HadOCC. The ocean carbon cycle is of interest largely because it concerns the biological processes by which some carbon is stored in the deep ocean. These simulators have dierent input spaces and model the system dierently, and standard emulation proves to be unable to compare them. The first method for two simulators, hierarchical emulation, works with pairs of simulators for which one is an extension of the other, and therefore whose input spaces are mostly similar. This uses the relationship between the simulators to emulate the more complex as a sum of the simpler simulator and some newly created functions. Validation studies using hierarchical emulators to model two versions of HadOCC show that the hierarchical emulator outperforms the standard methods in modelling both the extended simulator and the dierence between the two. The second, intermediate variable emulation, makes no constraint on the relationship between the simulators, instead making connections using sub-processes represented in both. This allows the representations of a system by two simulators to be directly compared; the contributions of the dierent sub-processes can be contrasted, and the sub-processes themselves can be used to gain better understanding of the relationship between the two input spaces. Intermediate variable emulators are used to compare OG99NPZD and HadOCC. Finally, to enable an ecient and robust implementation of these methods, as well as of the standard emulation method, an object-oriented framework for emulation is presented

Tuberculosis and Poverty: Why Are the Poor at Greater Risk in India?

Background: Although poverty is widely recognized as an important risk factor for tuberculosis (TB) disease, the specific proximal risk factors that mediate this association are less clear. The objective of our study was to investigate the mechanisms by which poverty increases the risk of TB. Methods: Using individual level data from 198,754 people from the 2006 Demographic Health Survey (DHS) for India, we assessed self-reported TB status, TB determinants and household socioeconomic status. We used these data to calculate the population attributable fractions (PAF) for each key TB risk factor based on the prevalence of determinants and estimates of the effect of these risk factors derived from published sources. We conducted a mediation analysis using principal components analysis (PCA) and regression to demonstrate how the association between poverty and TB prevalence is mediated. Results: The prevalence of self-reported TB in the 2006 DHS for India was 545 per 100,000 and ranged from 201 in the highest quintile to 1100 in the lowest quintile. Among those in the poorest population, the PAFs for low body mass index (BMI) and indoor air pollution were 34.2% and 28.5% respectively. The PCA analysis also showed that low BMI had the strongest mediating effect on the association between poverty and prevalent TB (12%, p = 0.019). Conclusion: TB control strategies should be targeted to the poorest populations that are most at risk, and should address the most important determinants of disease—specifically low BMI and indoor air pollution

How Methodologic Differences Affect Results of Economic Analyses: A Systematic Review of Interferon Gamma Release Assays for the Diagnosis of LTBI

Introduction: Cost effectiveness analyses (CEA) can provide useful information on how to invest limited funds, however they are less useful if different analysis of the same intervention provide unclear or contradictory results. The objective of our study was to conduct a systematic review of methodologic aspects of CEA that evaluate Interferon Gamma Release Assays (IGRA) for the detection of Latent Tuberculosis Infection (LTBI), in order to understand how differences affect study results. Methods: A systematic review of studies was conducted with particular focus on study quality and the variability in inputs used in models used to assess cost-effectiveness. A common decision analysis model of the IGRA versus Tuberculin Skin Test (TST) screening strategy was developed and used to quantify the impact on predicted results of observed differences of model inputs taken from the studies identified. Results: Thirteen studies were ultimately included in the review. Several specific methodologic issues were identified across studies, including how study inputs were selected, inconsistencies in the costing approach, the utility of the QALY (Quality Adjusted Life Year) as the effectiveness outcome, and how authors choose to present and interpret study results. When the IGRA versus TST test strategies were compared using our common decision analysis model predicted effectiveness largely overlapped. Implications: Many methodologic issues that contribute to inconsistent results and reduced study quality were identified in studies that assessed the cost-effectiveness of the IGRA test. More specific and relevant guidelines are needed in order to help authors standardize modelling approaches, inputs, assumptions and how results are presented and interpreted

High-frequency forcing of a turbulent axisymmetric wake

A high-frequency periodic jet, issuing immediately below the point of separation, is used to force the turbulent wake of a bluff axisymmetric body, its axis aligned with the free stream. It is shown that the base pressure may be varied more or less at will: at forcing frequencies several times that of the shear layer frequency, the time-averaged area-weighted base pressure increases by as much as 35 %. An investigation of the effects of forcing is made using random and phase-locked two-component particle image velocimetry (PIV), and modal decomposition of pressure fluctuations on the base of the model. The forcing does not target specific local or global wake instabilities: rather, the high-frequency jet creates a row of closely spaced vortex rings, immediately adjacent to which are regions of large shear on each side. These shear layers are associated with large dissipation and inhibit the entrainment of fluid. The resulting pressure recovery is proportional to the strength of the vortices and is accompanied by a broadband suppression of base pressure fluctuations associated with all modes. The optimum forcing frequency, at which amplification of the shear layer mode approaches unity gain, is roughly five times the shear layer frequency

Tuberculosis in pregnancy: an estimate of the global burden of disease

Background The estimated number of maternal deaths in 2013 worldwide was 289 000, a 45% reduction from 1990. Non-obstetric causes such as infectious diseases including tuberculosis now account for 28% of maternal deaths. In 2013, 3·3 million cases of tuberculosis were estimated to occur in women globally. During pregnancy, tuberculosis is associated with poor outcomes, including increased mortality in both the neonate and the pregnant woman. The aim of our study was to estimate the burden of tuberculosis disease among pregnant women, and to describe how maternal care services could be used as a platform to improve case detection. Methods We used publicly accessible country-level estimates of the total population, distribution of the total population by age and sex, crude birth rate, estimated prevalence of active tuberculosis, and case notifi cation data by age and sex to estimate the number of pregnant women with active tuberculosis for 217 countries. We then used indicators of health system access and tuberculosis diagnostic test performance obtained from published literature to determine how many of these cases could ultimately be detected. Findings We estimated that 216 500 (95% uncertainty range 192 100–247 000) active tuberculosis cases existed in pregnant women globally in 2011. The greatest burdens were in the WHO African region with 89 400 cases and the WHO South East Asian region with 67 500 cases in pregnant women. Chest radiography or Xpert RIF/MTB, delivered through maternal care services, were estimated to detect as many as 114 100 and 120 300 tuberculosis cases, respectively. Interpretation The burden of tuberculosis disease in pregnant women is substantial. Maternal care services could provide an important platform for tuberculosis detection, treatment initiation, and subsequent follow-up. Funding United States Agency for International Development

Does ethnicity, gender or age of physiotherapy students affect performance in the final clinical placements? An exploratory study

This is the post-print version of the final paper published in Physiotherapy. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 Elsevier B.V.Objectives - To explore demographic differences in awarded marks of the final clinical placement in a physiotherapy undergraduate programme. Design - Retrospective analysis of clinical placement assessment marks. Setting - A London university offering clinical placements throughout South East England. Participants - 333 physiotherapy students entering physiotherapy training between 2005 to 2009. Main outcome measures Marks awarded following assessment using a clinical placement assessment form. Results - The mean mark (SD) for age were standard entry 71 (7.4) vs. mature entry 72 (7.99) (ns); for gender male 72 (8.45) vs. female 71 (7.21) (ns); and ethnicity White British 72 (7.71) vs. ethnic minority 70 (7.01) (p = 0.023). No interaction effects were observed between the independent variables and only ethnicity demonstrated a statistically significant effect (mean difference (MD) 2.4% 95%CI 0.5 to 4.3, F = 5.24, p = 0.023). This difference was maintained in most subcategories. Significant differences were observed for the interpersonal section (MD 2.21% 95%CI 0.14 to 4.28, F = 4.409, p = 0.03), the clinical reasoning section (MD 2.39% 95%CI 0.53 to 4.25, F = 6.37, p = 0.012) and the treatment section (MD 2.93 95%CI 1.10 to 4.83, F = 9.198, p = 0.003). Conclusions - Physiotherapy students from minority ethnic backgrounds were awarded a significantly lower mark than their white majority peers in final clinical placements, although the difference was small. Potential reasons are considered, with the strongest recommendation being for further enquiry into the potential relationship between ethnicity and success in undergraduate physiotherapy education

Japanese Prime Ministerial Visits to Yasukuni Shrine in Sino-Japanese Relations

Prime Ministerial visits to Yasukuni Shrine is a pertinent issue and is critical in understanding the dynamics of Sino-Japanese relations. The casual mechanisms between Prime Ministerial visits to Yasukuni Shrine and the quality of Sino-Japanese relations is taken for granted and understudied in the literature. This study investigates the sensitivity interpretation casual mechanism through the hypothesis that Japanese Prime Ministerial visits (no visit) to Yasukuni Shrine is interpreted by China as insensitive (sensitive) about the past, which deteriorates (improves) Sino-Japanese relations. It engages in a comparative study between the Koizumi administration (2001-2006) and the Abe administration (2012-2020) to test this hypothesis, using primarily symbolic indicators including government statements, high-level meetings, and public opinion polls. The results demonstrate that the Chinese government interprets Prime Ministerial visits to Yasukuni Shrine as insensitive which deteriorates Sino-Japanese relations. However, the Chinese government appears to project this interpretation on the Chinese public. No visits by Japanese Prime Ministers to Yasukuni Shrine are interpreted by China as less insensitive, which is a strong necessary condition for the improvement of Sino-Japanese relations. These findings contribute to a deeper understanding of Sino-Japanese relations and can assist in the improvement of relations and building peace between China and Japan

Framework for the evaluation of new tests for tuberculosis infection

The scale-up of tuberculosis (TB) preventive treatment (TPT) must be accelerated to achieve the targets set by the United Nations High-level Meeting on TB and the End TB Strategy. The scale-up of effective TPT is hampered by concerns about operational challenges to implement the existing tests for TB infection. New simpler tests could facilitate the scale-up of testing for TB infection. We present a framework for evaluation of new immunodiagnostic tests for the detection of TB infection, with an aim to facilitate their standardised evaluation and accelerate adoption into global and national policies and subsequent scale-up. The framework describes the principles to be considered when evaluating new tests for TB infection and provides guidance to manufacturers, researchers, regulators and other users on study designs, populations, reference standards, sample size calculation and data analysis and it is also aligned with the Global Strategy for TB Research and Innovation adopted by the World Health Assembly in 2020. We also briefly describe technical issues that should be considered when evaluating new tests, including the safety for skin tests, costs incurred by patients and the health system patient, and operational characteristics

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority