Tesi sul tema "Heart"

Heart failure is a common and serious chronic condition, which can be as ‘malignant’ as most forms of cancer (Stewart, MacIntyre, Hole, Capewell, & McMurray, 2001). Recent estimates are that around 40,000 men and 45,000 women are living with heart failure in Scotland (Stewart, MacIntyre, Capewell, & McMurray, 2003). Heart failure is significantly influenced by socioeconomic factors, with people on lower incomes being more likely to develop, and die faster from, heart failure (McAlister et al, 2004). There is a growing body of research on the experience of living with heart failure, however, none provides serious consideration of the role of socioeconomic factors in impacting the experience of heart failure, and some qualitative research may actually obscure such factors. There were two main aims in this thesis. One was to explore how qualitative research methods can better consider the relationship between experience and broader context, such as the influence of socio-economic factors on health. The other aim was to examine the experiences of people as they live with and die from heart failure in ways that situate their accounts in the broader context of their lives. An initial research study, on which I was the main researcher, focused on the experiences of 30 people living with advanced heart failure. These people, their carers and key health professionals were interviewed, where possible, three times over a six months period. This thesis re-examines that study, focusing on 20 of those participants, for which a total of 122 interviews were conducted. I used a dialogical approach to see whether the socioeconomic context of heart failure for these respondents, could be captured through exploring experiences, performance, relationships, discourses and institutional practices, the social processes that mediate the relationship between socioeconomic disadvantage and chronic diseases were explored. This offers important learning in relation to the experience of living with heart failure, along with the experience of providing care. The findings highlight the need to broaden our view of chronic illness beyond biomedical approaches, and grow our methodological approaches along with that, in order to develop knowledge and practice that has relevance for people who live with and die from heart failure.

Insomnia is one of the most common complaints in medical practice and the sleep disorder of highest prevalence. At least 10% of the worldwide population has chronic insomnia, which has been associated with a range of negative health outcomes. Within the clinical setting, patient subtypes have been defined according to symptomology. More recently insomnia researchers have proposed phenotypes based on total sleep time during overnight polysomnography (PSG). Short-sleeping insomnia patients are purported to be a biologically severe phenotype at higher risk of cardiovascular morbidity, poor mental health, and obesity (compared to healthy controls). Heart rate variability (HRV) is an objective marker that provides insight into autonomic nervous system dynamics. The overarching aim of my research was to explore a large clinical sample of patients with Insomnia Disorder to determine whether differences in HRV exist during sleep in empirically-derived insomnia patient subtypes. The aim of the work presented within Chapter 2 was to identify all previous insomnia-HRV research to determine if HRV was impaired in adult patients with insomnia, and whether treatments altered HRV. A systematic review of five web databases located 22 relevant articles; 17 case-control studies and 5 interventions studies. Results were difficult to synthesise due to incomparable methodology and reporting. There was a high risk of bias in the majority of studies. It was concluded that although HRV impairment in insomnia may be a widely-accepted concept, it is not supported by research nor has it been determined if it varies after treatment or according to patient subtype. The aim of the first empirical study of the thesis (Chapter 3) was to objectively-derive insomnia patient subtypes and evaluate their physiological signals (HRV and electroencephalography [EEG]) during sleep onset. Patients (n = 96) with clinically-diagnosed Insomnia Disorder underwent overnight PSG to determine sleep metrics for cluster analysis using Ward’s method: Total Sleep Time (TST), Wake After Sleep Onset (WASO) and Sleep Onset Latency (SOL). Electrocardiogram (ECG) from the PSG was extracted in the 10 minutes before and after sleep onset. After R-wave detection, the ECG was visually checked and manually corrected as required. Six time and frequency-domain HRV measures were analyzed; heart rate (HR), standard deviation of all N-N intervals (SDNN), root mean square of successive R-R intervals (RMSSD), percentage of successive R-R intervals that differ by > 50 ms (PNN50), high frequency (HF), and low frequency (LF)/HF ratio. Cluster analysis derived two solutions; one comprising two subtypes and another with three subtypes. The two cluster solution consisted of insomnia with short-sleep duration (I-SSD: n = 43) and insomnia with normal objective sleep duration (I-NSD: n = 53). At sleep onset, between-group HRV analysis revealed reduced parasympathetic activity (PNN50 and RMSSD) in the short-sleeping subtype. This was not mirrored by significant increases in HR and/or the LF/HF ratio. These findings suggested that reduced parasympathetic activity during sleep onset might contribute to poor cardiometabolic health outcomes previously reported in short-sleeping insomnia patients. The final component of this thesis was a case-control study (Chapter 4) which examined whether HRV measures differed between insomnia subtypes across the nocturnal period. It was hypothesized that short-sleeping insomnia patients would have impaired HRV compared to normal-sleep duration insomnia patients, consistent with differences observed at sleep onset (Chapter 3). Insomnia patients underwent overnight PSG, which provided sleep metrics for cluster analysis and ECG for HRV analysis. ECG was visually checked for accurate R-wave detection, and manually corrected as required. HRV analysis was performed from lights-off to lights-on (and separately by sleep/wake stage) using time and frequency-domain measures. Differences in HRV measures (HR, SDNN, RMSSD, LF, HF, LF/HF) were tested between the subtypes using General Linear Models controlling for age as a core confounder. Short-sleeping insomnia patients (I-SSD: n = 34; 45.5 ± 10.5 years) and normal-sleep duration insomnia patients (I-NSD: n = 41; 37.6 ± 10.9 years) were included in the HRV analysis. There were no statistically significant nocturnal HRV differences between subtypes after controlling for age. As such, short-sleeping insomnia patients did not have statistically significant reductions in HRV measures representative of parasympathetic activity.«br /» In summary, there was a lack of persistent nocturnal HRV disparities (between empirically-derived insomnia patient subtypes) that extended beyond sleep onset in this large clinical sample of patients with Insomnia Disorder. The central tenet of 24-hour hyperarousal amongst short-sleep duration insomnia patients cannot be supported by the combined findings of these two empirical studies. Post-hoc calculations revealed larger sample sizes would be required to determine a small to medium effect size difference in nocturnal HRV between insomnia patient subtypes. Until this time, the directional relationship between insomnia, heart rate variability, hyperarousal and cardiovascular disease remains unclear in the heterogeneous insomnia population.

Heart transplantation has enjoyed a spectacular success over the past 25 years. Prior to 1980 less than 350 operations were carried out with an overall one year survival of less than 60%. In 1995 more than 3,000 transplants were performed with a one year survival of 83%. However, growth and improved survival have both plateaued over the last few years; the former because of the falling donor supply and the latter, in part, because of the use of less suitable donors in an effort to offset the problem of supply. Much attention has been focused on the drama of the surgery and the intricacies of immunological manipulation whilst little effort has been devoted to the area of donor management, despite the fact that primary graft failure is responsible for as many post transplant deaths as either infection or rejection. Optimum preservation of the donor heart has also provided a difficult challenge, such that, despite a considerable scientific effort little advance has been achieved to extend the 4 hour safe storage limit which has remained in place over the past 20 years. In this dissertation the problem has been approached by combining laboratory based preservation models with an objective regime of donor management. A sensitive isolated small animal working heart model was developed and used to characterise cardioplegic induction. Subsequently, the model was used to examine the interaction of oxygen content with the mode of delivery, during preservation. Finally, a number of representative solutions were combined with the most promising oxygen delivery method. These studies served to illustrate the utility of controlled laboratory studies and offer the prospect of more than doubling post storage function. The development of a rigorous donor management regime was also shown to be capable of reducing the variance in haemodynamic parameters by up to 44% whilst safely increasing the donor pool by approximately 30%. It is the contention of this thesis that the only prospect of improving the current impasse with the supply of donor hearts in sufficient quantity and of acceptable quality, is by the combination of appropriate laboratory models with controlled clinical trials.

Heart failure patients have dysfunction of the cardiac conduction system that contributes to a high burden of arrhythmias including atrial fibrillation and sudden cardiac death. Heart failure has been associated with the inflammatory response, but it is unknown if inflammation is playing a role in the remodelling of the cardiac conduction system in heart failure. Inflammation has been shown to be present in the myocardium from failing hearts and it is known to have detrimental effects on cardiac function, inducing fibrosis, remodelling of ion channels and even arrhythmias. However, the effect of inflammation on the cardiac conduction system has not been investigated. The aims of this study were to determine if there is an increase of pro-inflammatory cytokines and inflammatory cells in the cardiac conduction system in heart failure. In addition, to identify if there is possible inflammation-associated fibrosis and apoptosis in the cardiac conduction system in heart failure. To test these aims, three models of heart failure were used: a rat model of pulmonary arterial hypertension, a rabbit model of congestive heart failure and a rat model of myocardial infarction. In the rat model of pulmonary arterial hypertension there was a bradycardia, a prolongation of the QT interval, and an increase in the atrioventricular and ventricular refractory periods, suggesting electrical remodelling in these animals. The rats with pulmonary arterial hypertension displayed an increase in pro-inflammatory cytokines such as interleukins 1β and TGFβ in the right side of the heart, including the sinoatrial node and right Purkinje fibres of the cardiac conduction system. In addition, in these areas, there was an increase in components of the extracellular matrix, including fibronectin, collagen I and vimentin. Histology revealed regions of non-myocyte nuclei, only in the right ventricle of the rats with pulmonary arterial hypertension. Immunohistochemistry demonstrated patches of CD68 and vimentin expression (markers for macrophages and fibroblasts, respectively) in the right side of the heart in these animals. TUNEL staining also revealed an increase in apoptosis in the right side of the heart. In the rabbit model of congestive heart failure, the region most affected by inflammation was the right atrium, while few changes were measured in the ventricles or cardiac conduction system. Although these results are surprising, it is suggested that the atria could be more sensitive to the physical stretch produced in this model. In the rat model of myocardial infarction, there were regions of non-myocyte nuclei in the border zone. This region also had increases in pro-inflammatory and fibrosis markers. In conclusion, this work has presented the novel finding that there can be inflammation in the cardiac conduction system in heart failure. This could be contributing to the arrhythmias seen in heart failure patients. This could possibly lead the way to anti-inflammatories as a possible novel therapeutic for heart failure patients.

Pediatric congenital heart defects primarily occur during fetal heart embryological development. This purpose of this thesis was to provide a comprehensive review of the basic cardiovascular physiology, focusing on three separate components - the heart, the blood vessels, and the blood - and a current look at three common occurring conditions. The congenital heart defects are reviewed with an anatomical overview of the condition, patient presentation, current surgical repairs, and life expectancies following successful repair. Repairs of tetralogy of fallot report mortality rates below 3%, compared to a 50% mortality rate prior to development of surgical repairs (Apitz). Transposition of the great arteries repaired with the relatively new Nikaidoh procedure show 95% late survivability rates (Martins). For truncus arteriosus, currently 83% of patients survive past 15 years (Soriano). Continuing research and refinement of existing surgical techniques are expected to increase survivorship from this congenital heart defects. To help families and patients understand that congenital condition their loved one may have, a very easy to understand picture book was created. This can hopefully inspire further improvements in family resources to aid in comprehension of congenital heart diseases.

Hospital administrators strive to reduce readmission and over use of the acute care setting for chronic health conditions. Historically hospitals have focused on readmission prevention strategies to improve the transition of patients from the hospital to the community and although the causes of a hospital readmission may span multiple providers along the continuum of care, the hospital is currently the only provider being penalized. The project facility implemented a readmission reduction strategy, Re-Engineered Discharge (Project RED), as a means to reduce readmissions and yet continued to have high readmission rates for heart failure (HF) patients. The continued high rate of readmissions led to the practice focused question, which examined the process of developing a discharge phone call script specific for HF patients as a way to reduce readmissions for HF patients. Kristin Swanson's structure of caring model provided the nursing framework for this project with a purpose to plan a telephone call follow up program for HF patients after hospital discharge. The project planning was accomplished in conjunction with the facility's readmission reduction team/LEAN team, resulting in a script about the most prevalent issues among HF patients. Kotter's 8 step change model will be used as a guide for the implementation of the telephone call follow up program at a later date. Readmission rates for HF patients will be monitored monthly as an outcome evaluation measure. Project team members provided evaluation of the project which demonstrated satisfaction and success of the planning process. The results of this project will bring about social change by providing access to healthcare providers regardless the socioeconomic status of the patient and by decreasing the use of acute care setting unnecessarily for chronic conditions.

An artificial heart is a device that replaces the heart. Artificial hearts are typically used to bridge the time to heart transplantation, or to permanently replace the heart in case heart transplantation is impossible. Although other similar inventions preceded it are going back to the late 1940s, the first artificial heart to be successfully implanted in a human was the Jarvik-7, designed by Robert Jarvik and implemented in 1982. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/35027

Shark Heart is a manuscript of poems that maneuver between fearlessness and tenderness at the drop of a dime. In the same way that many sharks need to survive by constantly swimming in order to extract oxygen from the water streaming between their gills, the heart muscle needs to constantly pump blood throughout a body to sustain life: there is no rest for either fish or organ until death. These poems, too, keep pushing forward; they are not afraid to explore the small beats of childhood and hidden desire, or the larger mysteries of illness and death.
Master of Fine Arts

Basement Heart is a collection of short stories with a goal of documenting the manifestations of rage and how it evolves throughout a woman’s life. In these stories, femininity is explored through the aesthetics of the grotesque. Female protagonists seek to inhabit new definitions of female sexuality that combat tired expectations made by society’s misogynistic and objectifying culture. Often, their feelings of unprovoked grief manifest themselves as pursuits of the flesh, which becomes the underlying heartbeat of each story; themes revolve around sex and obsession and explore what happens when sexual fantasies are realized and lived out in the real world. When characters inhabit their bodies in ways that American culture tells women not to, they become viscerally self-aware and better their understanding of what they want. And doing what they want is all these women care about. The characters in Basement Heart are angry, restless, and at times driven mad by their own lust for control.

Thesis (Ph. D.)--University of Florida, 2001.
Title from first page of PDF file. Document formatted into pages; contains x, 99 p.; also contains graphics. Vita. Includes bibliographical references (p. 73-87).

Thesis (Ph.D.)--Oregon Health & Science University, 2005.
Includes bibliographical references (leaves 170-198). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.
Includes bibliographical references (leaves 69-71).
Heart rate variability (HRV), the beat-to-beat fluctuation of the heart rate, is a non-invasive test that measures the autonomic regulation of the heart. Assessment of HRV has been shown to predict the risk of mortality in patients after an acute myocardial infarction. Recently, the Krieger lab at MIT developed genetically engineered double knockout (dKO) mice that develop coronary artery disease accompanied by spontaneous myocardial infarctions and die at a very young age. This thesis investigated whether HRV could function as a prognostic indicator in the dKO mouse. A novel method for estimating physiological state of the mouse from the electrocardiogram using an innovative activity index was developed in order to compare HRV variables at different times while controlling for physiologic state. Traditional time and frequency domain variables were used to assess the prognostic power of HRV. Results have shown that none of the HRV variables were helpful in predicting mortality in the dKO mice. Mean heart rate showed some prognostic power, but it was not consistent in all the dKO mice. Finally, the activity index developed in this thesis provided a reliable metric for activity in mice as validated by a camera with motion detection.
by Laurence Zapanta.
S.M.

The aims of this study are to reveal the ‘method’ and ‘content’ of Ratzinger’s spiritual Christology, demonstrate how he applies method to content, and assess the validity and integrity of the resulting Christology. Chapter One offers an account of the various current critiques of Ratzinger’s Christology, which show that little attention has been paid to his spiritual Christology...

This thesis examined thermoregulatory responses in heart failure (HF) patients during exercise at a fixed relative intensity, and at an intensity that elicited a fixed rate of metabolic heat production (Hprod) in a warm environment (30°C). Additionally, the efficacy of a chronic, high-dose (5mg/d for 6wk) pharmacological intervention (folic acid supplementation) as a strategy for improving skin blood flow (SkBF) responses and thus, thermoregulatory control in these patients during exercise was assessed. The findings of three experiments conducted to achieve these aims are presented in this thesis. Experiment #1 was designed to compare thermoregulatory responses in HF and controls (CON) during exercise in the heat. Ten HF (New York Heart Association [NYHA] class I-II), and eight CON were included in the study. Core temperature (Tc), skin temperature (Tsk), and cutaneous vascular conductance (CVC – and index of SkBF) were assessed at rest and during one hour of cycling exercise at 60% of maximal oxygen uptake. Hprod and the evaporative requirements for heat balance (Ereq) were also calculated. Whole-body sweat rate (WBSR) was determined from pre-post nude body mass corrected for fluid intake. While Hprod (HF: 3.9 ± 0.9; CON: 6.4 ± 1.5 W/kg) and Ereq (HF: 3.3 ± 0.9; CON: 5.6 ± 1.4 W/kg) were lower (p < 0.01) for HF compared to CON, both groups demonstrated a similar rise in Tc (HF: 0.9 ± 0.4; CON: 1.0 ± 0.3°C). Despite this similar rise in Tc, Tsk (HF: 1.6 ± 0.7; CON: 2.7 ± 1.2°C), and the elevation in CVC (HF: 1.4 ± 1.0; CON: 3.0 ± 1.2 au/mmHg) were lower (p < 0.05) in HF compared to CON. Additionally, WBSR (HF: 0.36 ± 0.15; CON: 0.81 ± 0.39 L/h) was lower (p = 0.02) in HF compared to CON; however, was similar when corrected for differences in Ereq (p = 0.83). Collectively, these data suggest that patients with HF maybe limited in their ability to manage a thermal load and distribute heat content to the body surface (i.e., skin), secondary to impaired circulation to the periphery. Experiment #2 was designed to examine thermoregulatory responses in HF and CON during exercise at a fixed rate of Hprod, and therefore Ereq, in a 30°C environment. A total of 20 men; 10 HF and 10 CON similar in body size, were included in the study. Rectal temperature (Trec), local sweat rate (LSR), and CVC were measured throughout 60-min of cycle ergometry. WBSR was estimated from pre-post nude body weight corrected for fluid intake. Despite exercising at the same rate of Hprod (HF: 338 ± 43; CON: 323 ± 31 W, p = 0.25), the rise in Trec was greater (p < 0.01) in HF (0.81 ± 0.16°C) than CON (0.49 ± 0.27°C). In keeping with a similar Ereq (HF: 285 ± 40; CON: 274 ± 28 W, p = 0.35), no differences in WBSR (HF: 0.45 ± 0.11; CON: 0.41 ± 0.07 L/h, p = 0.38) or LSR (HF: 0.96 ± 0.17; CON: 0.79 ± 0.15 mg/cm2 /min, p = 0.50) were observed between groups. However, the rise in CVC was lower in HF than CON (HF: 0.83 ± 0.42; CON: 2.10 ± 0.79 au/mmHg, p < 0.01). Additionally, the cumulative body heat storage estimated from partitional calorimetry was similar between groups (HF: 154 ± 106; CON: 196 ± 174 kJ, p = 0.44). Collectively, these findings demonstrate that HF patients exhibit a blunted SkBF response, but no differences in sweating. Given that HF had similar body heat storage to controls at the same Hprod, their greater rise in core temperature can be attributed to a less uniform internal distribution of heat between the body core and periphery. In light of the findings of Experiments #1 and #2, Experiment #3 was subsequently designed to examined the effect of folic acid supplementation (5mg/d for 6wk) on vascular function (brachial artery flow-mediated dilation [FMD]), and SkBF responses (CVC) during 60-min of exercise at a fixed Hprod (300 W) in a 30°C environment in 10 HF (NYHA class I-II) patients and 10 CON. Serum folic acid concentration increased in HF (pre-intervention: 1.4 ± 0.2; post-intervention: 8.9 ± 6.7 ng/ml, p = 0.01) and CON (pre-intervention: 1.3 ± 0.6; post-intervention: 5.2 ± 4.9 ng/ml, p = 0.03). FMD improved by 2.1 ± 1.3% in HF (p < 0.01), but no change was observed in CON postintervention (p = 0.20). During exercise, the external workload performed on the cycle ergometer to attain the fixed level of Hprod for exercise was similar between groups (HF: 60 ± 13; CON: 65 ± 20 W, p = 0.52). Increases in CVC during exercise were similar in HF (pre: 0.89 ± 0.43; post: 0.83 ± 0.45 au/mmHg, p = 0.80) and CON (pre: 2.01 ± 0.79; post: 2.03 ± 0.72 au/mmHg, p = 0.73), although the values were consistently lower in HF for both pre- and post-intervention measurement intervals (p < 0.05). Furthermore, mean arterial pressure was similar in HF (pre: 98 ± 5; post: 94 ± 5 mmHg, p = 0.53) and CON (pre: 102 ± 3; post: 100 ± 3 mmHg, p = 0.65), and no differences were observed between groups during both exercise trials (all p > 0.05). These findings demonstrate that folic acid improves vascular endothelial function in patients with HF, but does not enhance SkBF during exercise at a fixed Hprod in a warm environment. The work presented in this thesis serves to expand our current understanding of the mechanisms responsible for impaired thermoregulatory control, particularly during exercise in the heat, in patients with HF. Furthermore, whilst folic acid did not serve to improve thermoregulatory SkBF during exercise in HF, folic acid improved vascular endothelial function to a greater extent in HF than CON. These data indicate that while folic acid does not alleviate the development of thermal strain during exercise in HF, its utility as a viable treatment option for reducing and/or preventing disease-related changes in vascular endothelial function in these patients warrants further investigation.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School Allied Health Sciences
Griffith Health
Full Text

Ein gesunder Herzschlag zeichnet sich nicht dadurch aus, dass er besonders regelmäßig ist. Vielmehr sollte ein gesunder Herzschlag, selbst in Phasen augenscheinlicher körperlicher Inaktivität, variabel sein (z.B. Appelhans & Luecken, 2006; Berntson et al., 1997; Shaffer, McCraty, & Zerr, 2014). Historisch gesehen ist dies keine völlig neue Erkenntnis – bereits in der frühen chinesischen und griechischen Medizin konnte dieses Phänomen beobachtet werden (einen schönen Überblick hierzu gibt Billman, 2011). Das Zusammenwirken der sympathischen und parasympathischen Bestandteile des autonomen Nervensystems, welches sich unter anderem in der Herzratenvariabilität (HRV) widerspiegelt, erlaubt uns nicht nur Einblicke in die physiologische Adaptionsfähigkeit, sondern auch in die psychische Flexibilität und Regulationsfähigkeit des Menschen, um so auf sich ständig ändernde Umweltanforderungen angemessen reagieren zu können (z.B. Appelhans & Luecken, 2006; Beauchaine, 2001; ChuDuc, NguyenPhan, & NguyenViet, 2013; Porges, 1995b; Quintana & Heathers, 2014; Riganello, Garbarino, & Sannita, 2012; Shaffer et al., 2014; Stein & Kleiger, 1999; Thayer & Lane, 2000). Mit ganz einfachen Worten: Die Variabilität unseres Herzschlages stellt eine Art Interface dar, welches Auskunft über das Zusammenspiel physiologischer und psychologischer Prozesse gibt. In der vorliegenden Monografie beschäftige ich mich intensiv mit dem Thema HRV, insbesondere mit der Anwendung und Durchführung von HRV-Kurzzeitmessungen (meistens fünf Minuten) im Kontext (bio-) psychologischer Forschung. Während ich im Rahmen des ersten Kapitels eine komprimierte Einführung in die Thematik und einen Überblick über die nachfolgenden Kapitel gebe, beschäftigt sich Kapitel II mit der Frage, welche methodischen Standards für HRV-Kurzzeitmessungen derzeit vorliegen. Ausgangspunkt hierfür sind vereinzelte Hinweise (z.B. im Rahmen meta-analytischer Bestrebungen) darauf, dass die Erfassung, Darstellung und Interpretation von HRV-Messungen durch ein nicht unerhebliches Maß an Diversität gekennzeichnet ist (z.B. de Vries, 2013; Ellis, Zhu, Koenig, Thayer, & Wang, 2015; Quintana & Heathers, 2014; Tak et al., 2009; Zahn et al., 2016). Ferner fehlen bis heute belastbare Normwerte für die gängigsten HRV-Parameter, die typischerweise in Kurzzeitmessungen berechnet werden können (vgl. Nunan, Sandercock, & Brodie, 2010). Ausgehend von diesen Beobachtungen stellen wir ein systematisches Literaturreview vor. In einem ersten Schritt haben wir aktuelle Standards zur Erhebung und Auswertung von HRV-Messungen identifiziert, auf deren Basis wir ein Klassifikationssystem zur Beurteilung von HRV-Studien erstellt haben. Nachfolgend wurden zwischen 2000 und 2013 publizierte Artikel (N = 457), im Hinblick auf die extrahierten methodischen Standards, überprüft. Unsere Ergebnisse legen das Vorhandensein einer beträchtlichen methodischen Heterogenität und einen Mangel an wichtigen Informationen nahe (z.B. in Bezug auf die Erhebung essentieller Kontrollvariablen oder das Berichten von HRV-Parametern), einhergehend mit der Tatsache, dass sich gängige Empfehlungen und Richtlinien (z.B. Task Force, 1996) nur partiell in der empirischen Praxis wiederfinden. Auf der Grundlage unserer Ergebnisse leiten wir Empfehlungen für weitere Forschung in diesem Bereich ab, wobei sich unsere „Checkliste“ besonders an forschende Psychologen richtet. Abschließend diskutieren wir die Einschränkungen unseres Reviews und unterbreiten Vorschläge, wie sich diese - bisweilen unbefriedigende - Situation verbessern lässt. Während unserer umfangreichen Literaturrecherche ist uns sehr schnell aufgefallen, dass HRV-Kurzzeitmessungen auf ein breites wissenschaftliches Interesse stoßen, wobei verschiedenste Konzepte und Forschungsfragen mit spezifischen HRV-Mustern in Verbindung gebracht werden (vgl. Beauchaine, 2001; Dong, 2016; Francesco et al., 2012; Makivić, Nikić, & Willis, 2013; Nunan et al., 2010; Pinna et al., 2007; Quintana & Heathers, 2014; Sammito et al., 2015; Sandercock, 2007). Darunter befinden sich sowohl eher eigenschaftsähnliche (z.B. Trait-Angst; Miu, Heilman, & Miclea, 2009; Watkins, Grossman, Krishnan, & Sherwood, 1998) als auch stark situationsabhängige Konstrukte (z.B. akute emotionale Erregung; Lackner, Weiss, Hinghofer-Szalkay, & Papousek, 2013; Papousek, Schulter, & Premsberger, 2002). Während die beiden einflussreichsten Theorien zur HRV, die Polyvagal-Theorie (Porges, 1995b, 2001, 2007) und das Modell der neuroviszeralen Integration (Thayer & Lane, 2000, 2009), einen dispositionellen Charakter der HRV nahelegen, sind zahlreiche Einflussfaktoren bekannt, die unmittelbare Auswirkungen auf das autonome Nervensystem haben (Fatisson, Oswald, & Lalonde, 2016; Valentini & Parati, 2009). Demzufolge haben wir uns die Frage gestellt, wie zeitlich stabil individuelle HRV-Messungen sind (siehe Kapitel III). Da die existierende Literatur hierzu ambivalente Ergebnisse bereithält (Sandercock, 2007; Sandercock, Bromley, & Brodie, 2005) und die zeitliche Stabilität von HRV-Messungen bisher vornehmlich über sehr kurze Zeiträume mit wenigen Messzeitpunkten untersucht wurde (z.B. Cipryan & Litschmannova, 2013; Maestri et al., 2009; Pinna et al., 2007), haben wir eine längsschnittliche Studie mit fünf Messzeitpunkten, verteilt auf ein Jahr, konstruiert (N = 103 Studierende). In Abhängigkeit von der Körperhaltung der Probanden während der Messung (liegend, sitzend, stehend), haben wir nachfolgend die Retest-Reliabilität (absolute und relative Reliabilität; siehe Atkinson & Nevill, 1998; Baumgartner, 1989; Weir, 2005) der gängigsten HRV-Parameter ermittelt. Unsere Ergebnisse deuten auf ein beachtliches Ausmaß an Zufallsschwankungen der HRV-Parameter hin, welches weitgehend unabhängig von der Körperhaltung der Probanden und dem zeitlichen Abstand der Messzeitpunkte ist. Da diese Ergebnisse weitreichende Folgen suggerieren, diskutieren wir diese, unter Berücksichtigung vorhandener Einschränkungen, ausführlich. Während in Kapitel II und III vornehmlich methodische Fragen im Fokus stehen, stelle ich in Kapitel IV dieser Monografie eine Feldstudie vor. Im Rahmen dieser Studie haben wir die Zusammenhänge zwischen subjektivem Stress, Coping-Strategien, HRV und Schulleistung untersucht. Sowohl die bereits erwähnten Theorien (Porges, 1995b, 2001, 2007, Thayer & Lane, 2000, 2009), als auch eine beträchtliche Anzahl an Forschung, lassen Zusammenhänge zwischen HRV und Stress (z.B. Berntson & Cacioppo, 2004; Chandola, Heraclides, & Kumari, 2010; Krohne, 2017; Michels, Sioen, et al., 2013; Oken, Chamine, & Wakeland, 2015; Porges, 1995a; Pumprla, Howorka, Groves, Chester, & Nolan, 2002) sowie HRV und kognitiver Leistung vermuten (z.B. Duschek, Muckenthaler, Werner, & Reyes del Paso, 2009; Hansen, Johnsen, & Thayer, 2003; Luque-Casado, Perales, Cárdenas, & Sanabria, 2016; Shah et al., 2011). Allerdings fehlt es bislang an Studien, welche die komplexeren Zusammenhänge zwischen all den genannten Konstrukten untersuchen. Dies gilt insbesondere für die Untersuchung von Kindern und Jugendlichen. Um zur Schließung dieser Wissenslücke beizutragen, haben wir Gymnasiasten (N = 72, zwischen zehn und 15 Jahren alt) im Rahmen eine Querschnittstudie zu deren Stresserleben und Bewältigungsstrategien (mittels SSKJ 3-8; Lohaus, Eschenbeck, Kohlmann, & Klein-Heßling, 2006) befragt. Außerdem wurden bei all diesen Schülern HRV und Zeugnisdurchschnittsnoten erhoben. Unsere Ergebnisse unterstreichen die Bedeutung konstruktiver Coping-Strategien zur Vermeidung von physischen und psychischen Stresssymptomen, welche ihrerseits negative Auswirkungen auf die Schulleistung haben. Demgegenüber lassen sich die erwarteten Zusammenhänge zwischen HRV und Stress/Coping (Berntson & Cacioppo, 2004; Dishman et al., 2000; Fabes & Eisenberg, 1997; Lucini, Di Fede, Parati, & Pagani, 2005; Michels, Sioen, et al., 2013; O’Connor, Allen, & Kaszniak, 2002; Porges, 1995a) sowie HRV und kognitiver Leistung (Hansen et al., 2003; Suess, Porges, & Plude, 1994; Thayer, Hansen, Saus-Rose, & Johnsen, 2009) anhand unserer Daten nicht bestätigen. Mögliche Gründe für dieses Befundmuster sowie Anforderungen an zukünftige Studien dieser Art werden abschließend diskutiert. Schlussendlich (a) fasse ich alle gesammelten Erkenntnisse prägnant zusammen, (b) diskutiere deren Implikationen, (c) stelle deren Beitrag zum wissenschaftlichen Forschungsstand heraus, und (d) gebe einen kurzen Einblick in die jüngsten Entwicklungen der HRV-Forschung (Kapitel V). Außerdem, und damit schließe ich den inhaltlichen Part dieser Monografie ab, möchte ich den Leser an meinen zehn wichtigsten Lernerfahrungen teilhaben lassen.

A young American woman goes to China looking for quiet and respite from campus activism but finds herself drawn into a love triangle with two Chinese dissidents. Through these relationships she becomes involved in the explosive demonstrations at Tiananmen Square and her life will never be the same.

Proefschrift Rijksuniversiteit Groningen.
Auteursnaam op omslag: Freddy van der Veen. Kop titelpagina vermeldt: Rijksuniversiteit Groningen. Datum laatste controle: 02-07-1997. Met lit. opg. - Met een samenvatting in het Nederlands.

Thesis (S.M. in Science Writing)--Massachusetts Institute of Technology, Dept. of Humanities, Graduate Program in Science Writing, 2010.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 22-31).
A few decades ago, black holes were a theoretical quirk. Highly probable on paper, they were doubted more than touted; many scientists didn't believe they even existed. Today, however, black holes appear to be everywhere, from behemoths in the cores of almost every galaxy to more modest, stellar-mass objects spattering the Milky Way's arms. Astronomers suspect that super massive black holes like Sagittarius A* (the compact dark object at the center of our galaxy) may be a cosmic mafia manipulating the galaxies that house them, possibly even controlling galaxy growth. If this suspicion turns out to be true, black holes may have had more influence on cosmic structure than any other object. This thesis explores how black holes became science from pseudoscience, focusing on three shifts in astronomy: detailed proper motion measurements of stars zooming around the galactic center, the discovery of the apparent relationship between galaxies and their central super massive black holes, and the development of working numerical simulations of black hole mergers. These three steps have led up to the Event Horizon Telescope, a project which will combine radio telescopes around the world to peer into the innermost spacetime warps surrounding Sagittarius A*. If all goes well, astronomers may finally glimpse the "silhouette" of the Milky Way's central super massive black hole within the next decade, directly testing whether Einstein's theory of general relativity is right.
by Camille M. Carlisle.
S.M.in Science Writing

In the past two years my paintings have fluctuated from figuration to abstraction. Dense surfaces, physical weight, and sense of touch have been dominant characteristics of my work. I have tried to animate oil paint by pushing it to the outer edges of the painting support and by using it to perform unorthodox tasks. I have stretched the limits of oil paint, creating works that reference flesh and the figure even while the forms remain amorphous and minimal. My work is a way for me to question the meaning of material and spiritual transformation.

It is my discovery of the mandala that has had the most significant influence on me as an artist. The mandala, Sanskrit word for circle or center, is found in a majority of my pieces, either literally or symbolically. My interest in and subsequent use of the mandala began twenty years ago and continues to this day. The mandala is a primordial image found in the macrocosm of the universe, the microcosm of nature, and in the psyche of man. The circle has been used throughout the world in image and architecture as a sacred symbol since the beginning of time.

Thesis (M.M.)--Conservatory of Music and Dance. University of Missouri--Kansas City, 2008.
For alto saxophone and string quartet. "A thesis in music composition." Advisor: Chen Yi. Typescript. Duration: 15:00. Vita. Title from "catalog record" of the print edition Description based on contents viewed Apr. 14, 2009. Online version of the print edition.

Healthcare practices are changing as focus shifts fromtreating acute illnesses to chronic diseases. Theresponsibility of managing the treatment has shifted fromhealthcare providers to the individual in a higher degree. Toachieve good treatment the patients need to be empoweredso that they understand their condition and can makeinformed choices throughout their self-care. A researchthrough design approach was used to investigate how todesign a personalized empowering application for heartfailure patients. Aside from information relating to thecondition, the themes of physical activity, dieting and socialconnectedness were identified as central to address for theempowerment of this group. Patients, partners andhealthcare providers contributed with different perspectivesthroughout the design process. As a result five personas,representing potential users, were developed. Based on thepersonas and knowledge of the domain, user scenarios incurrent- and preferred state were constructed in order toguide the design of the empowering application called ‘TheHeart Companion’. It is a tablet application catering to thedifferent needs of the personas that also addresses the threethemes relevant for empowerment. The purpose of theapplication is to facilitate better understanding, a feeling ofsafety and a more active empowered life for the patient.The application enables personalization of the content byproviding bookmarking and addresses empowerment ofphysical activity by enabling various guided exercisesessions, personalized feedback, the possibility of reflectionand construction of personalized exercise sessions.
Sjukvårdens praxis förändras i takt med att fokus skiftar från behandling av akuta sjukdomar till kroniska sjukdomar. Ansvaret för behandling av kroniska sjukdomar har överförts från vårdgivare till att inbegripa individen till en högre grad. För att uppnå god behandling måste patienterna stärkas så att de förstår sitt tillstånd och kan fatta välgrundade beslut i sin egenvård. ’Research through design’ användes som metod för att undersöka hur en personifierad stärkande applikation för hjärtsviktspatienter kan utformas. Bortsett från information om tillståndet så identifierades fysisk aktivitet, kosthållning och social samhörighet som centrala teman att adressera för att stärka denna grupp. Patienter, partners och vårdgivare bidrog med olika perspektiv under designprocessen. Som ett resultat utav detta utvecklades fem personas för att representera potentiella användare. Baserat på personorna och kunskap om domänen så konstruerades användarscenarion i det nuvarande- samt det föredragna tillståndet för att vägleda designen av den stärkande applikationen som kallas Hjärtkompanjonen. Hjärtkompanjonen är en tablet-applikation som tillmötesgår de olika personornas behov och som även tar upp de tre teman som är relevanta att införliva för att stärka hjärtsviktspatienter. Syftet med applikationen är att åstadkomma bättre förståelse, en känsla av säkerhet och ett mer aktivt stärkt liv för patienten. Applikationen möjliggör personalisering av innehållet genom att tillhandahålla bokmärkning och adresserar hur en patient kan stärkas vid fysisk aktivitet genom att öppna upp för olika guidade träningspass, personlig feedback, möjligheter till reflektion samt konstruktion av personliga träningspass.

Imaging modalities such as CT, MRI, and SPECT have had a tremendous impact on diagnosis and treatment planning. These imaging techniques have given doctors the capability to visualize 3D anatomy structures of human body and soft tissues while being non-invasive. Unfortunately, the 3D images produced by these modalities often have boundaries between the organs and soft tissues that are difficult to delineate due to low signal to noise ratios and other factors. Image segmentation is employed as a method for differentiating Regions of Interest in these images by creating artificial contours or boundaries in the images. There are many different techniques for performing segmentation and automating these methods is an active area of research, but currently there are no generalized methods for automatic segmentation due to the complexity of the problem. Therefore hand-segmentation is still widely used in the medical community and is the €œGold standard€� by which all other segmentation methods are measured. However, existing manual segmentation techniques have several drawbacks such as being time consuming, introduce slice interpolation errors when segmenting slice-by-slice, and are generally not reproducible. In this thesis, we present a novel semi-automated method for 3D hand-segmentation that uses mesh extraction and surface parameterization to project several 3D meshes to 2D plane . We hypothesize that allowing the user to better view the relationships between neighboring voxels will aid in delineating Regions of Interest resulting in reduced segmentation time, alleviating slice interpolation artifacts, and be more reproducible.

An early detection of heart disease can save lives, caution individuals and also help to determine the type of treatment to be given to the patients. The first test of diagnosing a heart disease is through auscultation - listening to the heart sounds. The interpretation of heart sounds is subjective and requires a professional skill to identify the abnormalities in these sounds. A medical practitioner uses a stethoscope to perform an initial screening by listening for irregular sounds from the patient's chest. Later, echocardiography and electrocardiography tests are taken for further diagnosis. However, these tests are expensive and require specialized technicians to operate. A simple and economical way is vital for monitoring in homecare or rural hospitals and urban clinics. This dissertation is focused on developing a patient-centered device for initial screening of the heart sounds that is both low cost and can be used by the users on themselves, and later share the readings with the healthcare providers. An innovative mobile health service platform is created for analyzing and classifying heart sounds. Certain properties of heart sounds have to be evaluated to identify the irregularities such as the number of heart beats and gallops, intensity, frequency, and duration. Since heart sounds are generated in low frequencies, human ears tend to miss certain sounds as the high frequency sounds mask the lower ones. Therefore, this dissertation provides a solution to process the heart sounds using several signal processing techniques, identifies the features in the heart sounds and finally classifies them. This dissertation enables remote patient monitoring through the integration of advanced wireless communications and a customized low-cost stethoscope. It also permits remote management of patients' cardiac status while maximizing patient mobility. The smartphone application facilities recording, processing, visualizing, listening, and classifying heart sounds. The application also generates an electronic medical record, which is encrypted using the efficient elliptic curve cryptography and sent to the cloud, facilitating access to physicians for further analysis. Thus, this dissertation results in a patient-centered device that is essential for initial screening of the heart sounds, and could be shared for further diagnosis with the medical care practitioners.

The optimal therapy for atrial fibrillation (AF) associated with heart failure (HF) is unclear. Drug-based rhythm control has not proved clinically beneficial. Catheter ablation-based rhythm control improves cardiac function in HF patients, but impact on physiological performance has not been formally evaluated in a randomised trial. A randomised trial was designed and conducted, comparing catheter ablation with rate control in adults with symptomatic heart failure, radionuclide left ventricular ejection fraction (EF) ≤35%, and persistent AF. The primary outcome was change in peak oxygen consumption (VO2) at cardiopulmonary exercise test. Secondary endpoints included change in quality of life (Minnesota), 6-minute walk, BNP, and EF. Patients were followed-up for 12 months, and results analysed by intention-to-treat. 52 patients (63±9y, EF 24±8%, VO2 17.3±5.1ml/kg/min) were randomised, 26 to each arm. In the ablation arm, at 12 month follow up, 88% maintained SR, with a single procedure success of 69%. In the rate control arm, rate criteria were achieved in 96% at 12 months. At 12 months, peak VO2 had increased by 2.13 (95%CI -0.1 to 4.36) ml/kg/min in the ablation arm, compared with a decrease (-0.94ml/kg/min, 95%CI -2.21 to 0.32) under rate control: mean benefit of ablation +3.07ml/kg/min, 95% CI 0.56-5.59, p=0.018. The change appeared progressive, with a difference of only 0.79ml/kg/min at 3 months (95% CI -1.01 to 2.60, p=0.38). Compared with rate control, ablation reduced 12-month Minnesota score (p=0.019) and BNP (p=0.045), and showed trends toward increased 6 min walk distance (p=0.095) and EF (p=0.055). LA size fell significantly after ablation (p=0.001). Catheter ablation of persistent AF in patients with HF, with the ablation strategy achieving sinus rhythm in the majority, improves prognostically important objective cardiopulmonary exercise performance, symptoms and neurohormonal status. The effects are clear at 1 year but less distinct earlier, suggesting a period of cardiac remodelling and recovery.

Background While the prevalence of heart failure (HF) in Europe and the USA has increased constantly in the last decades up to 12 million patients, we are still missing available, effective therapeutic options for advanced HF refractory to medical management, accounting for 5% of the total HF patient population. In fact, cardiac transplantation remains the primary option for a select group of end-stage HF patients but it is strongly limited due to the shortage of donor organs. The research in the field of mechanical devices to support or substitute the pumping function of failing heart is therefore strongly pursued. Since the end of the 90’s, thanks to the improved performance and safety of left ventricular assist devices (LVADs), their clinical use has increased both as a bridge to cardiac transplantation (BTT) and as a lifelong therapy. In case of end-stage biventricular failure or candidates with restrictive or infiltrative cardiomyopathies with ventricular cavities too small to accommodate apical inflow cannulae, LVADs are not a viable option: bi-ventricular assist devices (BiVAD) or total artificial hearts (TAH) are needed. To date, in INTERMACS records, only less than 5% of implanted mechanical circulatory support devices are BiVAD or TAH; however these figures do not reflect the real need for total replacement of heart function due to the limitations of available TAH (SynCardia). State of the Art The only clinically available TAH to date is the pneumatically driven SynCardia, that was FDA approved for BTT in 2004. It requires no surgical pocket, can provide up to 10 L/min flow with physiological control through both pulsatile pumping chambers. However, the TAH requires adequate mediastinal space to accommodate the dual-chambered pump. Its last generation portable pneumatic controller allows patients to be discharged from the hospital, although patients’ quality of life is limited by noise and weight of the drive unit (6 kg) that they need to carry. Device malfunction, along with bleeding, stroke, and infection, remain concerns with this technology. New TAHs research and development Several new TAH projects were started and stopped at different stage of development such as Abiomed Abiocor, Cliveland Clinic Foundation Magscrew, Aachen AME ReinHeart, only to quote few recent ones. Either technical issues prevented projects to get regulatory approval for clinical use or lack of research funding did not allow project completion. At the time being, Carmat TAH (Carmat SA) is undergoing pre-clinical tests. It is an implantable, electro-hydraulically driven, pulsatile flow device with four bioprosthetic valves. The stroke volume (30–65 ml) and the beat rate (35–150 b/min) of the prosthesis adapt automatically in response to changes in preload and the resulting pulsatile blood flow ranges from 2 to 9 l/min. Its blood-pumping surfaces consist of processed bioprosthetic pericardial tissue, potentially allowing for the reduction of anti-coagulation. Despite such innovative aspect, the implantable pump is huge and needs sternum-to-vertebral column minimum distance of 13 cm to be implanted. Conclusion: Padua Heart Project In order to provide an innovative solution in the field of MCS, Padua Heart Project (PHP) pursues the design of a small size, electromechanically driven TAH, that can deliver pulsatile blood flow to meet physiological need. While all of the above mentioned TAH projects are based on rotary motors with a conversion gear, thus consisting of many wear-prone parts, limiting their durability, PHP is based on a linear motor having only one moving component. Due to its original design and control mode, the size of the linear motor can be only slightly larger than the blood sacs. Furthermore, its inner lining can be coated by processed pericardial tissue. As a proof of concept, a first linear drive prototype was developed and set up. The movable part of the linear motor consists of a flat magnet including two valvular prostheses. Its linear movement back and forward within the driving coil, allows compression and relaxation of a flexible blood sac and its filling and emptying through the valves. The prototype has been tested in a simple mock loop to deliver flow varying between 4.5 and 7.5 L/min with 120 mmHg of afterload. Further tests are under way to optimize blood sac shape and control mode at different sets of preload and afterload conditions.
Studio dello stato dell’arte del cuore artificiale totale (TAH) nella pratica clinica: la ricerca bibliografica è stata orientata all’analisi delle più recenti esperienze cliniche con TAH per individuarne limiti e punti di forza. L’obiettivo di tale ricerca documentale era quello di dedurre le specifiche per un nuovo TAH, in grado di soddisfare le esigenze terapeutiche ancora parzialmente o totalmente irrisolte dai sistemi attualmente disponibili: • CARATTERISTICHE DI PESO E INGOMBRO IDEALI: diametro <90 mm, lunghezza < 100 mm; peso < 800 gr (peso del cuore naturale 300- 400 gr), per poter essere impiantato anche in pazienti di piccola BSA • ATTUATORE impiantabile, elettromeccanico, efficiente, silenzioso, in grado di produrre un flusso medio di circa 6 L/min contro una pressione media di circa 100 mmHg, con capacità di sostenere sovraccarichi e picchi di flusso, con bassa dissipazione di calore verso il sangue e i tessuti • DISEGNO DELLE CAMERE VENTRICOLARI E DELLE VALVOLE rispetto al flusso ematico tale da minimizzare l’emolisi e le zone di stagnazione del flusso e il conseguente pericolo di formazione di trombi • MATERIALI USATI BIO ED EMOCOMPATIBILI: plastica, metallo, materiale biologico (PERICARDIO DECELLULARIZZATO), con caratteristiche di non tossicità, non carcinogenicità, stabilità chimica e resistenza meccanica, sterilizzabilità • INTERFACCIA DEL TAH con il circolo (atri, arterie) rispettosa dell’anatomia e con agevoli meccanismi di aggancio • DURATA DISPOSITIVO : circa 5 anni (per un sistema pulsatile, ciò corrisponde ad un numero di cicli variabile tra 225 e 350 Milioni, a seconda che lo Stroke Volume vari tra 70 e 45 ml), per poter offrire un supporto di lungo termine Studio di nuovi modelli di TAH ancora in corso di sviluppo e ricerca brevettuale su TAH innovativi: attraverso tale ricerca sono stati individuati gli spunti più interessanti tra le tecnologie in divenire ed è stato definito come orientare il progetto del TAH di Padova. In particolare, si è optato per un sistema con pompe volumetriche, a camere flessibili valvolate, azionate da motori elettrici lineari (quindi, con meno trasduzioni) di piccole dimensioni. L’attuazione prevede un movimento push-pull del piano delle valvole, che realizza contemporaneamente il riempimento e l’eiezione dalle camere ventricolari. Questo consente, a parità di ingombro, l’aumento della portata o, viceversa, a parità di portata una considerevole riduzione di volume della pompa. Sono stati disegnate diverse possibili configurazioni della pompa push-pull e infine viene scelta soluzione con movimento dei piani valvolari, interposti tra sacco ventricolare e “atri”, disposti a “U”,con frequenza minima 60 b/min, SV 80 ml (40ml +40ml). Primi test su banco: il sistema push-pull con uno stroke volume complessivo di 80 ml ottenuto attraverso 2 eiezioni successive di 40 ml ciascuna, con frequenza di salita/discesa del motore lineare di 60b/min (1Hz) riesce a pompare 4,8 L/min contro un afterload di 120 mmHg Aumentando la frequenza a 92b/min, il sistema riesce a erogare una portata di 7.2 L/min contro lo stesso postcarico Emerge l’originalità progettuale del disegno in cui le valvole si comportano sia da organi di intercettazione sia da elementi di spinta della massa fluida. Prove su banco di confronto Drive Units di dispositive in uso clinico (Cardiowest Companion vs Freedom): sono state eseguite prove su banco di unità di controllo differenti impiegate sullo stesso modello di TAH (Cardiowest) allo scopo di individuare le variabili di controllo salienti su cui basare il sistema di attuazione del nuovo TAH. Lo spunto è stato fornito da un reale “clinical dilemma”: il paziente 1Z, a cui era stato impiantato il CardioWest nel 2007, ha iniziato a manifestare problemi di dispnea con edema polmonare, nonostante un flusso di 5 L/min, appena è passato dal sistema di attuazione Companion al più recente Freedom. Non aveva tali sintomi coi precedenti drive units Excor e Companion; nessun altro organo presentava segnali di scompenso. Le prove su banco hanno dimostrato che la più recente drive unit (Freedom), essendo molto rigida, poiché non permette la regolazione delle pressioni di attuazione dei due ventricoli, e non avendo alcun feedback sulle pressioni di riempimento del paziente, può determinare squilibri tra circolo destro e sinistro. Appare quindi molto importante nel progetto di nuovo TAH includere la possibilità di modulazione della portata in funzione delle pressioni di riempimento. Progetto di fitting virtuale del TAH: lo studio si propone di convertire TAC del torace in un modello 3D semplice rapido e affidabile della cavità toracica. I risultati attesi consistono nella definizione ottimale degli ingombri e delle forme della protesi impiantabile del TAH che si sta progettando, incluse le interfacce con atri e grandi vasi del ricevente. Inoltre, lo strumento sarebbe disponibile per la determinazione ottimale pre-operatoria del fitting anatomico in un dato paziente di un dato sistema di supporto circolatorio impiantabile. La ricerca è stata avviata in collaborazione con l’Unità di Ricerca “3DOM” della Fondazione Bruno Kessler di Trento.

Cardio-embolic stroke accounts for nearly a third of all ischaemic strokes. The most clinically important cardio-embolic sources are non-valvular atrial fibrillation (AF) and chronic heart failure. Strokes due to these conditions are associated with greater disability and more mortality, as compared to stroke of other aetiology. This thesis is aimed at addressing some of the challenges faced by clinicians when dealing with stroke in patients with AF or heart failure, using an extensive range of historical data. Chapter 1 provides an introduction to stroke, AF and heart failure, including current prevalences, aetiology, and their complex intertwine relationship. The current acute stroke management in patients with AF or heart failure is also outlined within the chapter. In chapter 2, the data sources and statistical methods that were common to the studies in the thesis are outlined. The justifications of using historical data in the absence of evidence from robust clinical trials are also detailed. Chapter 3 explores the relevance of antithrombotic treatment on patterns and outcomes of acute stroke patients with AF. A non-randomised cohort analysis was conducted using data from the Virtual International Stroke Trials Archive (VISTA). The associations of antithrombotic treatment with the modified Rankin scale (mRS) outcome, and the occurrence of recurrent stroke and symptomatic intracerebral haemorrhage, at 90 days after stroke were described. Combined sequential antithrombotic therapy (i.e. oral anticoagulant and antiplatelet treatment), was associated with favourable outcome on ordinal mRS and significantly lower risk of recurrent stroke, symptomatic intracerebral haemorrhage and mortality by day 90, compared to the patients who did not receive any antithrombotic treatment. The relative-risk of recurrent stroke and symptomatic intracerebral haemorrhage appeared highest in the first 2 days after stroke before attenuating to become constant over time. Thus, early introduction of oral anticoagulant treatment (2-3 days after stroke), and to a lesser extent antiplatelet agents, was associated with substantially fewer recurrent stroke events over the following weeks but with no excess risk of symptomatic intracerebral haemorrhage. Chapter 4 seeks to describe the current prescribing patterns in stroke survivors with AF, with particular emphasis on socio-demographic associations. A cross-sectional analysis of city-wide Glasgow primary care data for the year 2010, was conducted. This chapter highlights that oral anticoagulant treatment was under-used in this high risk population, especially those of older age and affected by deprivation. Strategies need to be developed to improve prescription of oral anticoagulant treatment. Chapter 5 investigates the incidence of stroke within the available heart failure trials spanning a 30 year period, according to AF status at baseline. Individual patient data were pooled from 11 trials conducted in patients with heart failure and reduced ejection fraction (HF-REF); and, 3 trials performed in patients with heart failure and preserved ejection fraction (HF-PEF). Stroke incidence has not significantly declined over time in patients with HF-REF enrolled to trials, despite greater use of evidence-based heart failure and oral anticoagulant therapies. However, anticoagulation proportions remain under 70% among HF-REF patients with documented AF. Similar trends of stroke incidence were observed for patients enrolled in HF-PEF trials. Some patients with heart failure but without atrial fibrillation may be at high risk of stroke and may potentially benefit from oral anticoagulant treatment. Chapter 6 provides a comprehensive description of the current incidence of and risk factors for stroke in patients with HF-REF but without AF. Data from two large and contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiac- Heart Failure trial (GISSI-HF), were pooled to enable the analysis. The new simple clinical predictive model for stroke showed that about one-third of patients without AF have a risk of stroke similar to patients with AF. The predictive model was also validated in an independent large data set. The high risk of stroke in patients without AF might be reduced by individualised and safer oral anticoagulant treatment. Correspondingly, Chapter 7 explores the risk-model for stroke in a contemporary cohort of patients with HF-PEF but without AF. Data were pooled from the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity- Preserved trial (CHARM-Preserved) and the Irbesartan in Heart Failure with Preserved Systolic Function trial (I-Preserve), for patients with ejection fraction ≥45% only. The analysis showed that the simple clinical model developed in Chapter 6, for patients with HF-REF, is also applicable to patients with HF-PEF. There are concerns that systemic thrombolysis might not achieve clinically-important outcome among chronic heart failure patients with acute ischaemic stroke. Chapter 8 evaluates the relevance of chronic heart failure on the outcome of acute stroke patients who received thrombolysis. A non-randomised cohort analysis was conducted using data obtained from the Virtual International Stroke Trials Archive (VISTA). The associations of outcome among chronic heart failure patients with thrombolysis treatment using the mRS distribution at day 90, stratified by presence of AF, were evaluated. Chronic heart failure was associated with a worse outcome with or without thrombolysis. However, acute stroke patients who received thrombolysis had more favourable outcome regardless of heart failure status, compared to their untreated peers. The findings should reassure clinicians considering systemic thrombolysis treatment in hyper-acute ischaemic stroke patients with chronic heart failure. This thesis has summarised and extended our knowledge of the complex relationship between stroke and the heart, focusing on atrial fibrillation and heart failure. It has answered many questions and generated many more. The reported studies may assist clinicians who are dealing with stroke in patients with atrial fibrillation or heart failure. These conditions are common and each carry poor prognosis. Thus, even small advances in their treatment may have a useful societal impact.

Background and hypothesis: Standard pharmacological treatment for heart failure improves cardiac remodelling and survival in the setting of chronic heart failure, but is suboptimal in cases of acute heart failure (AHF). Peripartum cardiomyopathy (PPCM), de-novo hypotension (often due to haemorrhagic shock), and Takotsubo cardiomyopathy (TC) are conditions which have acute onset of heart failure, and often present with high mortality rates. In patients treated for these pathologies, a variation in the heart rate is observed and could potentially be used as a target to improve the treatment of AHF. We therefore questioned whether the use of a sinoatrial node inhibitor (ivabradine) to modulate heart rate may improve outcomes in AHF. Objectives and methods: Our objectives were 3-fold: (1) to explore the effect of a standard treatment strategy on heart rate in a South African cohort of PPCM patients after 6 and 12 months follow-up. (2) To explore the effect of ivabradine, a sinoatrial node inhibitor in an established signal transducer and activator of transcription 3 (STAT3) knockout mouse model of PPCM (with 3 consecutive pregnancies). Mice were fed ivabradine for 30 days (10mg/kg/day in drinking water), following the 3rd weaning. Trans-thoracic echocardiograms (TTE) were done at the end of the 3rd weaning, and after 30 days of treatment with ivabradine. Hearts were harvested after the second TTE for histology staining and messenger ribonucleic acid (mRNA) quantitation of transcripts involved in heart failure. (3) To explore the role of the sinoatrial node inhibitor in an ex-vivo model of de-novo AHF due to hypotension, and a newly developed ex-vivo model of TC. In the AHF model, hearts were stabilised before administering Ivabradine (3μM) in a buffer containing high free fatty-acids at a low pressure (to mimic hypotension/ haemorrhage shock conditions). A pressure- sensing balloon in the left ventricle measured heart rate, diastolic and systolic pressure, left ventricular developed pressure, rate pressure products and functional recovery. In the TC model, hearts were stabilised, then given a buffer with high free fatty-acid content and 10 times a physiological dose of adrenaline to mimic the adrenergic response seen in TC. Thereafter, hearts were restored to stabilisation pressure and substrate for recovery. Results: (1) Clinical outcomes indicated that patients on maximum standard therapy improved symptomatically and on the New York Heart Association scale. However, heart rates of PPCM patients remained elevated after 6 months of treatment. (2) In PPCM mice, a treatment with ivabradine was associated with reduced fibrotic infiltration in cardiac tissue and with a decrease in levels of atrial natriuretic peptide and Fibronectin mRNAs. (3) Both hypotensive AHF and TC models showed a tendency toward better cardiac function with ivabradine at the end of the acute phases. This advantage was lost after withdrawal of ivabradine during recovery. Conclusion: In South African women with PPCM treated with standard therapy, heart rate remains elevated, therefore suggesting that these women may benefit from the use of ivabradine as an additional therapy, particularly in patients who may be intolerant to β-blockers. The long-term use of ivabradine in the setting of cardiac dysfunction appears to have beneficial effects on remodelling, as treatment with ivabradine in our mouse PPCM model showed reduced cardiac fibrosis. The ex-vivo models of hypotensive AHF and TC both showed benefit in reducing heart rate during the acute phases, and hold the potential of being an intervention therapy to improve the outcome in patients who are brought to hospital while still in the acute phase.

This thesis critically comments on the unapologetic consumerist society that is feeding the obesity epidemic in the United States. Utilizing the medium of animation, this work displays the paradox advertisement creates by enticing individuals into an unhealthy life style, while simultaneously shaming their excessive indulgence by exhibiting images of ideals. The appealing surface level of this piece masks the dark underlying implications, similar to the colorful boxes of food that disguise illness as nourishment.

Hyperlipidemia is prevalent following heart transplantation, and may play a role in the development of late graft atherosclerosis. The charts of 35 heart transplant recipients (n = 32 males and 3 females) were reviewed retrospectively up until three years post transplantation, to describe a time-course of hypercholesterolemia after transplantation, and to determine the mechanisms involved in its pathogenesis. All patients received prednisone, cyclosporine, and azathioprine for immunosuppression. A progressive rise in both serum cholesterol (2.4 $ pm$ 0.4 mmol/l, p $<$ 0.01), and body weight (8.4 $ pm$ 1.6 kg, p $<$ 0.01) were observed during the first 8 and 10 months respectively. Levels stabilized thereafter, remaining above pretransplant levels. Triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations were all above normal limits following transplantation. Tapering of prednisone dose had a significant effect on serum cholesterol levels, whereas diet had a beneficial effect on body weight. A randomized, controlled, dietary intervention study then followed to further assess the effect of dietary intervention on minimizing or preventing post transplantation hyperlipidemia and weight gain. Five patients were counselled the Step One Lipid-Lowering diet, two patients were controls. All study patients demonstrated a lower overall increase in serum cholesterol levels than other transplant recipients. Reported nutritional intakes were similar between both groups. Increases in body weight were related to increases in body fat. Patients in the diet group demonstrated improvements in their level of nutrition knowledge, which correlated with lower serum cholesterol levels. Changes in serum cholesterol were also associated with appetite, hunger, perceived interest, perceived benefits, perceived barriers, and attitudes toward food. Changes in body weight were associated with appetite, hunger, perceived barriers, and stress. As