Four pieces of music with critical commentary

This thesis was submitted for the degree of Master of Philosophy and awarded by Brunel University.The commentaries contained in this volume supplement the four pieces of chamber music I composed in my research toward the Master of Philosophy degree. Those pieces, in chronological order of completion, are It Plays You for saxophone quartet, I Am the Rose of Sharon for six voices and string trio, The Opposite of the World for eleven instruments, and Trying to get the feeling back that I had in 1972 for solo viola. The commentaries aim to establish the cultural suppositions on whose basis these pieces were conceived, the technical and aesthetic considerations that informed their composition, and the strategies by which they advance the author's critical project

Short runs of atrial arrhythmia and stroke risk: a European-wide online survey among stroke physicians and cardiologists

Methods: An online survey of cardiologists and stroke physicians was carried out to assess current management of patients with short runs of atrial arrhythmia within Europe. Results: Respondents included 311 clinicians from 32 countries. To diagnose atrial fibrillation, 80% accepted a single 12-lead ECG and 36% accepted a single run of < 30 seconds on ambulatory monitoring. Stroke physicians were twice as likely to accept < 30 seconds of arrhythmia as being diagnostic of atrial fibrillation (OR 2.43, 95% CI 1.19–4.98). They were also more likely to advocate anticoagulation for hypothetical patients with lower risk; OR 1.9 (95% CI 1.0–3.5) for a patient with CHA2DS2-VASc = 2. Conclusion: Short runs of atrial fibrillation create a dilemma for physicians across Europe. Stroke physicians and cardiologists differ in their diagnosis and management of these patients

Risk Stratification in Post-MI Patients Based on Left Ventricular Ejection Fraction and Heart-Rate Turbulence

Objectives: Development of risk stratification criteria for predicting mortality in post-infarction patients taking into account LVEF and heart-rate turbulence (HRT). Methods: Based on previous results the two parameters LVEF (continuously) and turbulence slope (TS) as an indicator of the HRT were combined for risk stratification. The method has been applied within two independent data sets (the MPIP-trial and the EMIAT-study). Results: The criteria were defined in order to match the outcome of applying LVEF ( 30 % in sensitivity. In the MPIP trial the optimal criteria selected are TS normal and LVEF ( 21 % or TS abnormal and LVEF ( 40 %. Within the placebo group of the EMIAT-study the corresponding criteria are: TS normal and LVEF ( 23 % or TS abnormal and LVEF ( 40 %. Combining both studies the following criteria could be obtained: TS normal and LVEF ( 20 % or TS abnormal and LVEF ( 40 %. In the MPIP study 83 out of the 581 patients (= 14.3 %) are fulfilling these criteria. Within this group 30 patients have died during the follow-up. In the EMIAT-trial 218 out of the 591 patients (= 37.9 %) are classified as high risk patients with 53 deaths. Combining both studies the high risk group contains 301 patients with 83 deaths (ppv = 27.7 %). Using the MADIT-criterion as classification rule (LVEF ( 30 %) a sample of 375 patients with 85 deaths (ppv = 24 %) can be selected. Conclusions: The stratification rule based on LVEF and TS is able to select high risk patients suitable for implanting an ICD. The rule performs better than the classical one with LVEF alone. The high risk group applying the new criteria is smaller with about the same number of deaths and therefor with a higher positive predictive value. The classification criteria have been validated within a bootstrap study with 100 replications. In all samples the rule based on TS and LVEF (= NEW) was superior to LVEV alone, the high risk group has been smaller (( s: 301 ( 14.5 (NEW) vs. 375 ( 14.5 (LVEF)) and the positive predictive value was larger (( s: 27.2 ( 2.6 % (NEW) vs. 23.3 ( 2.2 % (LVEF)). The new criteria are less expensive due to a reduced number of high risk patients selected

Detection of temporal-lobe epilepsy with the physiological responses to fear and anxiety

Epilepsy is a neurological disease caused by an abnormal neuronal activity on a region of the brain, which provokes seizures and the loss of consciousness to its patients. Epilepsy can be very disabling, since patients do not know when crisis or seizures are going to occur. The epilepsy we will focus on is "temporal lobe epilepsy", which is caused because of an abnormal neuronal activity on the temporal lobe. Before the development of an onset, the brain's temporal lobe -and consequently, the amygdala- are activated. Once having assured the relationship between the amygdala and an onset, the project will analyse the relationship between high levels of fear and anxiety -related with amygdala functions- and the development of a seizure. After determining what the relationship between fear and anxiety and the start of the seizure is, the project aims to develop a device that can do that by itself. The device will detect the patients' heart rate -since it is the main reaction to fear- and, when the heart rate is high enough to develop into a seizure, it will warn the patient. Thanks to that, epilepsy patients will live less anxious, since they will know when a seizure is going to happen and they will be able prevent themselves from the damages which might occur

Prevalence of and Risk Factors for Paroxysmal Atrial Fibrillation in Patients with Cardiovascular Disease but without diagnosed Atrial Fibrillation

学位記番号：医博甲172

Modifiable predictors of ventricular ectopy in the community

Background Premature ventricular contractions (PVCs) predict heart failure and death. Data regarding modifiable risk factors for PVCs are scarce. Methods and Results We studied 1424 Cardiovascular Health Study participants randomly assigned to 24-hour Holter monitoring. Demographics, comorbidities, habits, and echocardiographic measurements were examined as predictors of PVC frequency and, among 845 participants, change in PVC frequency 5 years later. Participants exhibited a median of 0.6 (interquartile range, 0.1-7.1) PVCs per hour. Of the more directly modifiable characteristics and after multivariable adjustment, every SD increase in systolic blood pressure was associated with 9% more PVCs (95% confidence interval [CI], 2%-17%; P=0.01), regularly performing no or low-intensity exercise compared with more physical activity was associated with ≈15% more PVCs (95% CI, 3-25%; P=0.02), and those with a history of smoking exhibited an average of 18% more PVCs (95% CI, 3-36%; P=0.02) than did never smokers. After 5 years, PVC frequency increased from a median of 0.5 (IQR, 0.1-4.7) to 1.2 (IQR, 0.1-13.8) per hour ( P<0.0001). Directly modifiable predictors of 5-year increase in PVCs, described as the odds per each quintile increase in PVCs, included increased diastolic blood pressure (odds ratio per SD increase, 1.16; 95% CI, 1.02-1.31; P=0.02) and a history of smoking (OR, 1.31; 95% CI, 1.02-1.68; P=0.04). Conclusions Enhancing physical activity, smoking cessation, and aggressive control of blood pressure may represent fruitful strategies to mitigate PVC frequency and PVC-associated adverse outcomes

Clinical and molecular characterization of a cardiac ryanodine receptor founder mutation causing catecholaminergic polymorphic ventricular tachycardia

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth. Objectives We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation. Methods Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with β-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload–induced calcium release activity of the mutant channel in HEK293 cells. Results We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload–induced calcium release activity under conditions that mimic catecholaminergic stress. Conclusion Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on β-adrenergic stimulation

Cost-effectiveness of 7-day-Holter monitoring alone or in combination with transthoracic echocardiography in patients with cerebral ischemia

Background and purpose Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis. Methods: Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198). Results: Predicted lifelong discounted costs were 33,837 € for patients diagnosed by the 7-d-Holter and 33,852 € by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 €/QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness. Conclusions: A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness