The dynamics of dwarf spheroidal galaxies

Digitisation of this thesis was sponsored by Arcadia Fund, a charitable fund of Lisbet Rausing and Peter Baldwin

Does increased provider effort improve quality of care? Evidence from a standardised patient study on correct and unnecessary treatment

BACKGROUND: Poor quality of care, including overprovision (unnecessary care) is a global health concern. Greater provider effort has been shown to increase the likelihood of correct treatment, but its relationship with overprovision is less clear. Providers who make more effort may give more treatment overall, both correct and unnecessary, or may have lower rates of overprovision; we test which is true in the Tanzanian private health sector. METHODS: Standardised patients visited 227 private-for-profit and faith-based facilities in Tanzania, presenting with symptoms of asthma and TB. They recorded history questions asked and physical examinations carried out by the provider, as well as laboratory tests ordered, treatments prescribed, and fees paid. A measure of provider effort was constructed on the basis of a checklist of recommended history taking questions and physical exams. RESULTS: 15% of SPs received the correct care for their condition and 74% received unnecessary care. Increased provider effort was associated with increased likelihood of correct care, and decreased likelihood of giving unnecessary care. Providers who made more effort charged higher fees, through the mechanism of higher consultation fees, rather than increased fees for lab tests and drugs. CONCLUSION: Providers who made more effort were more likely to treat patients correctly. A novel finding of this study is that they were also less likely to provide unnecessary care, suggesting it is not simply a case of some providers doing "more of everything", but that those who do more in the consultation give more targeted care

A Bayesian framework for emergent constraints: case studies of climate sensitivity with PMIP

In this paper we introduce a Bayesian framework, which is explicit about prior assumptions, for using model ensembles and observations together to constrain future climate change. The emergent constraint approach has seen broad application in recent years, including studies constraining the equilibrium climate sensitivity (ECS) using the Last Glacial Maximum (LGM) and the mid-Pliocene Warm Period (mPWP). Most of these studies were based on ordinary least squares (OLS) fits between a variable of the climate state, such as tropical temperature, and climate sensitivity. Using our Bayesian method, and considering the LGM and mPWP separately, we obtain values of ECS of 2.7 K (0.6–5.2, 5th–95th percentiles) using the PMIP2, PMIP3, and PMIP4 datasets for the LGM and 2.3 K (0.5–4.4) with the PlioMIP1 and PlioMIP2 datasets for the mPWP. Restricting the ensembles to include only the most recent version of each model, we obtain 2.7 K (0.7–5.2) using the LGM and 2.3 K (0.4–4.5) using the mPWP. An advantage of the Bayesian framework is that it is possible to combine the two periods assuming they are independent, whereby we obtain a tighter constraint of 2.5 K (0.8–4.0) using the restricted ensemble. We have explored the sensitivity to our assumptions in the method, including considering structural uncertainty, and in the choice of models, and this leads to 95 % probability of climate sensitivity mostly below 5 K and only exceeding 6 K in a single and most uncertain case assuming a large structural uncertainty. The approach is compared with other approaches based on OLS, a Kalman filter method, and an alternative Bayesian method. An interesting implication of this work is that OLS-based emergent constraints on ECS generate tighter uncertainty estimates, in particular at the lower end, an artefact due to a flatter regression line in the case of lack of correlation. Although some fundamental challenges related to the use of emergent constraints remain, this paper provides a step towards a better foundation for their potential use in future probabilistic estimations of climate sensitivity

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label,parallel-group, multicentre trial

Background The benefi t of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not been systematically studied. We aimed to assess the eff ect of CTCA on the diagnosis, management, and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. Methods In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18–75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed in the group they were allocated to, irrespective of compliance with scanning. This study is registered with ClinicalTrials.gov, number NCT01149590. Findings Between Nov 18, 2010, and Sept 24, 2014, we randomly assigned 4146 (42%) of 9849 patients who had been referred for assessment of suspected angina due to coronary heart disease. 47% of participants had a baseline clinic diagnosis of coronary heart disease and 36% had angina due to coronary heart disease. At 6 weeks, CTCA reclassifi ed the diagnosis of coronary heart disease in 558 (27%) patients and the diagnosis of angina due to coronary heart disease in 481 (23%) patients (standard care 22 [1%] and 23 [1%]; p<0·0001). Although both the certainty (relative risk [RR] 2·56, 95% CI 2·33–2·79; p<0·0001) and frequency of coronary heart disease increased (1·09, 1·02–1·17; p=0·0172), the certainty increased (1·79, 1·62–1·96; p<0·0001) and frequency seemed to decrease (0·93, 0·85–1·02; p=0·1289) for the diagnosis of angina due to coronary heart disease. This changed planned investigations (15% vs 1%; p<0·0001) and treatments (23% vs 5%; p<0·0001) but did not aff ect 6-week symptom severity or subsequent admittances to hospital for chest pain. After 1·7 years, CTCA was associated with a 38% reduction in fatal and nonfatal myocardial infarction (26 vs 42, HR 0·62, 95% CI 0·38–1·01; p=0·0527), but this was not signifi cant. Interpretation In patients with suspected angina due to coronary heart disease, CTCA clarifi es the diagnosis, enables targeting of interventions, and might reduce the future risk of myocardial infarction. Funding The Chief Scientist Offi ce of the Scottish Government Health and Social Care Directorates funded the trial with supplementary awards from Edinburgh and Lothian’s Health Foundation Trust and the Heart Diseases Research Fund