Cardiovascular risk prediction in the Netherlands

Background: In clinical practice, Systematic COronary Risk Evaluation (SCORE) risk prediction functions and charts are used to identify persons at high risk for cardiovascular diseases (CVD), who are considered eligible for drug treatment of elevated blood pressure and serum cholesterol. These functions use classical risk factors (age, gender, smoking, blood pressure and the ratio of total-to-HDL-cholesterol) to predict absolute 10-year risk of CVD mortality rather than total (fatal plus nonfatal) CVD. The aim of this thesis was to improve cardiovascular risk prediction in the Netherlands and to correctly classify high-risk persons. Methods: We primarily used data from the Monitoring Project on Chronic Disease Risk Factors (MORGEN project) of the National Institute for Public Health and the Environment (RIVM). Risk factor data of more than 20,000 men and women aged 20-65 years were collected between 1993 and 1997. Ten-year follow up data on CVD mortality and morbidity were obtained from Statistics Netherlands and the National Hospital Discharge Register, respectively. Risk functions were developed using multivariable Cox proportional hazard models. Results: The SCORE risk function for low-risk countries was the best predictor of CVD mortality in the Netherlands. Total CVD was approximately four times higher than CVD mortality. Obesity (BMI ≥30 kg/m2) and parental history of myocardial infarction before age 70 were independent predictors of total CVD. Risk functions predicting risk of CVD mortality and total CVD, and their ability to discriminate between future cases and non-cases, did not differ. Of the high-risk persons with a CVD mortality risk of at least 5%, approximately 20% developed a nonfatal or fatal CVD event during 10 years of follow-up. When a cut-off point of 2% CVD mortality was used, approximately 10% of the high-risk persons developed a CVD event. When obesity and parental history of MI were added to the classical risk factor function, correct risk classification improved by 5%. This improvement in risk prediction was mainly due to obesity. Conclusions: Discrimination between future cases and non-cases did not improve by expanding the endpoint of risk prediction from fatal CVD to total CVD. Adding obesity and parental history to the classical risk factor functions slightly increased the number of correctly classified persons. </p

The role of inclusions in ALS pathogenesis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that primarily afflicts motor neurons, leading to paralysis and death within 3 to 5 years after diagnosis. Genetic studies have uncovered multiple genetic defects causing familial forms of ALS and mutations occurring in proteins with a variety of functions, including RNA metabolism (TDP43, FUS) and oxygen free radical homeostasis (SOD1). A commonality among all ALS forms is the presence of intracellular inclusions that primarily consist of insoluble protein aggregates. These inclusions indicate that protein aggregation is a central pathogenic event shared by multiple ALS forms. The research of the present thesis focuses on the role of protein aggregation and inclusion formation in two types of ALS: 1) ALS caused by mutations in the superoxide dismutase 1 (SOD1) gene (ALS1); and 2) ALS caused by mutations in the vesicle-associated membrane protein (VAMP)-associated protein B (VAPB) gene (ALS8)

Анализ влияния теории информационных каскадов и стадного поведения агентов на формирование финансовых пузырей

Розглянуто питання формування фінансових бульбашок на основі ірраціональної поведінки економічних агентів та теорії інформаційних каскадів. Наведено базову модель інформаційних каскадів, характеристику та етапи утворення фінансових бульбашок. Ключові слова: прийняття рішень, стадна поведінка, фінансові ринки, інформаційний каскад, фінансові бульбашки.Рассмотрены вопросы формирования финансовых пузырей на основе иррациональных подходов стадного поведения экономических агентов и теории информационных каскадов. Приведена базовая модель информационных каскадов, характеристика и этапы образования финансовых пузырей. Ключевые слова: принятие решений, стадное поведение, финансовые рынки, информационный каскад, финансовые пузыри.The paper deals with formation of bubbles on the basis of irrational approaches of herd behaviour of the economic agents and the theory of information cascades. A basic model of information cascades is presented, as well as characteristics and stages in formation of financial bubbles. Keywords: decision making, herd bahaviour, financial markets, information cascade, financial bubbles

Stir in stillness : a study in the foundations of equilibrium statistical mechanics

The goal of this dissertation has been to investigate whether and how SM is (or can be made) a satisfactory theory for thermal phenomena of systems in equilibrium. This central research question splits into two separate parts: Can SM reproduce the empirically successful predictions of TD? And can it do so in a conceptually satisfactory way, i.e. by giving explanations in micromechanical terms? Now it is time to review whether this goal has been achieved. In the different parts of this dissertation I have treated different kinds of thermal phenomena, i.e. different parts of TD that SM has to reproduce. Part III dealt with the question why the phase averaging method is successful. This question addresses a very central feature of the statistical mechanical method, because it affects the relation between thermal obervables and ensemble theory. With respect to this topic only the second of the above questions had to be addressed, since the way in which thermodynamic results can be reproduced is undisputed here. With respect to the topics of Part II and Part IV also the question of how SM can reproduce thermodynamic predictions had to be addressed. The thermal phenomena at issue in these Parts are those connected to the notion of entropy, and the approach to equilibrium

Does an unconditioned stimulus memory devaluation procedure decrease disgust memories and conditioned disgust?:Results of two laboratory studies

Research has demonstrated that disgust can be installed through classical conditioning by pairing neutral conditioned stimuli (CSs) with disgusting unconditioned stimuli (USs). Disgust has been argued to play an important role in maintaining fear-related disorders. This maintaining role may be explained by conditioned disgust being less sensitive to extinction (i.e., experiencing the CS in the absence of the US). Promising alternatives to extinction training are procedures that focus on the devaluation of US memory representations. In the current study, we investigated whether such devaluation procedures can be successful to counter conditioned disgust. We conducted two laboratory studies (N = 120 and N = 51) in which disgust was conditioned using audio-visual USs. Memory representations of the USs were devalued by having participants recall these USs while they performed a taxing eye-movement task or executed one of several control tasks. The results showed successful conditioned disgust acquisition. However, no strong evidence was obtained that an US memory devaluation procedure modulates disgust memory and diminishes conditioned disgust as indicated by subjective, behavioral, or psychophysiological measures. We discuss the relevance of our results for methodological improvements regarding US memory devaluation procedures and disgust conditioning