University of Bristol

There are now a wide range of antidepressants used to treat depression in primary care, but the two main types influence the neurotransmitters serotonin (5HT) or noradrenaline. We plan to investigate whether there are genetic, clinical or hormonal predictors of response to these two main types of antidepressant. We plan to carry out a clinical trial that will randomise people with depression to either of the two antidepressants. The antidepressants are equally effective overall, but it seems that some patients get better on one type and some on the other. If we can find out what predicts response it will help to target treatment and also understand more about how these tablets work. It might also help to provide a classification of different types of depression.

tbc

When a piece of chalk is dragged across a blackboard, it is a matter of common, and usually unpleasant, experience that the chalk can judder and sometimes emit a high-pitched squeal. Such behaviour is related to the Painlevé paradox (Painlevé 1905). Physically, the frictional torque at the point of contact is high enough to overcome the resistance of the rigid surface, implying that the chalk should enter the blackboard. Since this cannot happen, the chalk jumps.The recent discovery that the paradox can occur in robotic manipulators, where it effects controllability, together with some excellent experimental evidence (Zhao et al. 2008), have provoked strong modern interest in this old problem.This project aims to deal with some outstanding issues relating to the Painlevé paradox. For a slender rod slipping on a rough surface, indeterminacy or inconsistency in the rigid body equations represent failures in modelling. The assumed rigidity must be relaxed. It has been shown by Hogan & Kristiansen (2016) that behaviour like that seen physically (e.g. instantaneous jumping of the chalk away from the board) arises when there is some compliance at the point of contact. This compliance (or regularization) is extremely small, and the resulting equations lead to a slow-fast system for which there is a wealth of existing mathematical theory. However, to capture the piecewise-smooth (PWS) limit of the rigid body, we need geometric singular perturbation theory, in which there have been many advances. The recently developed "blowup method" (Krupa & Szmolyan 2001) enables the identification of scales associated with the regularization, in a framework amendable to classical reduction methods in dynamical system theory. One outstanding problem that this project will aim to resolve was posed by Dupont & Yamajako (1997) of a rod between two rough surfaces. The aim is to build upon the framework in Hogan & Kristiansen (2016), where the underlying modelling assumptions of rigid body dynamics are relaxed and the PWS system is replaced by a smooth one through regularization. Then blowup will be used in the analysis of the problem.

In Malaysia the prevalence of obesity among adolescents is increasing and non-communicable diseases, like type 2 diabetes and cardiovascular disease, account for two out of three deaths. While research in European and US-based populations has found that particular lifestyle factors might cause adolescents to be fatter and less fit we do not have a complete picture of what causes these problems in Malaysia. In this study we are going to look at how different lifestyle factors, like foods eaten, timing or frequency of eating, physical activity, sedentary behaviours and their timing or location, combine together to create an overall behavioural pattern score that indicates whether adolescents have good health. We've previously found that a combination of factors is more important for health compared with single factors alone. Initial analysis of health outcomes will focus on obesity, blood pressure, and how much LDL cholesterol, fats and glucose are in blood samples. We also plan to use a new, reproducible laboratory technique, known as metabolomics, to measure 233 different components of blood that indicate a range of metabolic processes. This will help us find out in much more detail than ever before how behaviour leads to better cardiovascular health via metabolic pathways. When we know more about the pathway that leads from lifestyle to disease we will be better able to predict who will stay healthy and who will not. In this study, one of our aims is to find the main behaviours related to keeping a healthy metabolism and reducing the risk of cardiovascular disease in the future. We'll then work out how these behaviours can changed by an intervention. This research is possible because of a large study of over 1361 adolescents, called MyHeARTs. The aim of MyHeARTs was to identify which factors best predict health to enable the early detection and prevention of type 2 diabetes and cardiovascular disease. MyHeARTs started in 2012, collecting information on the behaviour and health of 1361 adolescents from 15 urban and rural schools in 3 regions of Malaysia and has just completed a third follow-up in 2016. The participants have provided detailed reports of their diet, activity, and other health behaviours as well as measurements of body composition, physical fitness and blood samples at age 13, 15 and 17, which we will use for this study. We are interested to see whether combinations of lifestyle behaviours can accurately predict changes in the blood chemical profile of participants as they progress through adolescence before they develop clear symptoms of cardiovascular disease or diabetes. Finally, within this project we lay the foundations for improving adolescents' metabolic health. We will talk to adolescents and school staff about how they could adopt the behaviours we found were important for health in MyHeART. We will then use their views paired with known methods of behaviour change to encourage a healthy lifestyle and prevent disease that will work in countries, like Malaysia, where resources are limited.

TBC- CDT student in first year. Will be updated when abstract written (Summer 2022) Prelimary / outline description: Indoor aerosols may contribute to negative health effects. This project will measure the physical and chemical nature of indoor aerosol pollutants produced within the home. Placements to conduct an epidemiological literature review and investigate the health effects of these aerosol will enable a risk analysis of the measured aerosol. Theme: Atmospheric and environmental aerosol