Design and Rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial

The Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short-term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double blind, placebo controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co., Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation

Seriously cool: marketing and communicating with diverse generations

Separating the generational hype and conjecture from the serious, usable research and analysis is a challenge. McCrindle Research report an increasing number of organisations identifying generation gaps as the cause of failed communication, ineffective marketing and even workplace conflict. Yet some commentators are beginning to question the practical applicability of generational segments. In response, McCrindle set out to research the generational segments and to explore a number of unresolved questions. 1. How does generational segmentation fit into more traditional market segmentation models? 2. How can marketers apply generational analysis without including sweeping generalisations that could render their marketing communications invalid and ineffective? 3. What are the emerging drivers of consumer behaviour amongst generational segments? 4. What trends can be observed in the media and communication consumption habits of the diverse generations? 5. What communication styles are most applicable to the diverse generations? This white paper provides a big-picture analysis of our changing times and generational shifts, and points to some of the drivers of the generational debate. In the process it delivers insights into both marketing strategy and the marketing and communication tactics that will result in deeper engagement with the diverse generations

Word Up: A Lexicon and Guide to Communication in the 21st Century

Many Australians knock young people for the unorthodox ways in which they use language and communicate. However, generations Y and Z are a product of our technological age, and their language simply reflects this. Unlike older generations, they have learned to adapt their spoken and written styles to technology. Technology isn’t the only force shaping language today. American culture, multiculturalism and globalisation continue to have a major impact (to be analysed in the second chapter). The lexicon at the back of the book contains youth slang in current use by generations Y and Z. If you are a Baby Boomer (born 1946–1964) or a member of Generation X (1965–1979), you will notice some words spawned by your own generation that you probably used as a young person (and perhaps still use), that have been adopted by gens Y and Z. You will also notice that the spelling, pronunciation and even meanings of many of these words have changed or evolved with the younger generations. To compile this lexicon we surveyed generations Y and Z and asked them for the key words they use – and the meanings. Our research showed that not all under 30s use all these words, however they are the words of these generations, shaped by their times

The ABC of XYZ: Understanding the Global Generations

Based on a more than a decade of research, this reference is designed for marketers, managers, educators, and parents who need a useful, fun, not-too-technical introduction to generational research. The breezy vocabulary of this kind of study is familiar to most people--Are Gen X-ers still slackers? Will Gen Y-ers ever move out of the house? Why are Zeds so spoiled?--but this guide goes deeper with explanations of how a generation is defined and the statistical tools that allow social scientists to track the behavior of its members over time. The discussion also provides examples of generational conflicts in school, home, and the workplace--and reveals how these clashes can be understood and resolved. Interspersed with useful tables and figures, the book also compares English-speaking countries with their generational counterparts in Japan, Finland, and other parts of the world

A chronological history of the school

This chapter introduces the Alpine School and its original purpose and goals before leading into the story of the historical development of the current School for Student Leadership (SSL). It outlines the extensive political background behind the creation of this unique Victorian school and the search for an appropriate principal. The development of the school from a single campus to the current three campuses is detailed, with photos of each included to illustrate the diverse environmental contexts that are represented. Also presented is an outline of some of the major differences in the curriculum and overall experience that students receive through a term spent at the SSL, compared to that offered via traditional mainstream education. The different learning opportunities resulting from a program that focuses on providing a rite of passage for adolescents and includes experiential learning, reflection and a Community Learning Project are discussed, illustrating the contemporary approach used at the school to meet the cognitive, physical, social and emotional needs of the attending Year 9 students

Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease.

Coronary artery thrombosis is the major risk associated with Kawasaki disease (KD). Long-term management of KD patients with persistent aneurysms requires a thrombotic risk assessment and clinical decisions regarding the administration of anticoagulation therapy. Computational fluid dynamics has demonstrated that abnormal KD coronary artery hemodynamics can be associated with thrombosis. However, the underlying mechanisms of clot formation are not yet fully understood. Here we present a new model incorporating data from patient-specific simulated velocity fields to track platelet activation and accumulation. We use a system of Reaction-Advection-Diffusion equations solved with a stabilized finite element method to describe the evolution of non-activated platelets and activated platelet concentrations [AP], local concentrations of adenosine diphosphate (ADP) and poly-phosphate (PolyP). The activation of platelets is modeled as a function of shear-rate exposure and local concentration of agonists. We compared the distribution of activated platelets in a healthy coronary case and six cases with coronary artery aneurysms caused by KD, including three with confirmed thrombosis. Results show spatial correlation between regions of higher concentration of activated platelets and the reported location of the clot, suggesting predictive capabilities of this model towards identifying regions at high risk for thrombosis. Also, the concentration levels of ADP and PolyP in cases with confirmed thrombosis are higher than the reported critical values associated with platelet aggregation (ADP) and activation of the intrinsic coagulation pathway (PolyP). These findings suggest the potential initiation of a coagulation pathway even in the absence of an extrinsic factor. Finally, computational simulations show that in regions of flow stagnation, biochemical activation, as a result of local agonist concentration, is dominant. Identifying the leading factors to a pro-coagulant environment in each case-mechanical or biochemical-could help define improved strategies for thrombosis prevention tailored for each patient

Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease.

Coronary artery thrombosis is the major risk associated with Kawasaki disease (KD). Long-term management of KD patients with persistent aneurysms requires a thrombotic risk assessment and clinical decisions regarding the administration of anticoagulation therapy. Computational fluid dynamics has demonstrated that abnormal KD coronary artery hemodynamics can be associated with thrombosis. However, the underlying mechanisms of clot formation are not yet fully understood. Here we present a new model incorporating data from patient-specific simulated velocity fields to track platelet activation and accumulation. We use a system of Reaction-Advection-Diffusion equations solved with a stabilized finite element method to describe the evolution of non-activated platelets and activated platelet concentrations [AP], local concentrations of adenosine diphosphate (ADP) and poly-phosphate (PolyP). The activation of platelets is modeled as a function of shear-rate exposure and local concentration of agonists. We compared the distribution of activated platelets in a healthy coronary case and six cases with coronary artery aneurysms caused by KD, including three with confirmed thrombosis. Results show spatial correlation between regions of higher concentration of activated platelets and the reported location of the clot, suggesting predictive capabilities of this model towards identifying regions at high risk for thrombosis. Also, the concentration levels of ADP and PolyP in cases with confirmed thrombosis are higher than the reported critical values associated with platelet aggregation (ADP) and activation of the intrinsic coagulation pathway (PolyP). These findings suggest the potential initiation of a coagulation pathway even in the absence of an extrinsic factor. Finally, computational simulations show that in regions of flow stagnation, biochemical activation, as a result of local agonist concentration, is dominant. Identifying the leading factors to a pro-coagulant environment in each case-mechanical or biochemical-could help define improved strategies for thrombosis prevention tailored for each patient

Arrhythmia and Mortality After the Mustard Procedure: A 30-Year Single-Center Experience

AbstractObjectives. Our purpose was to assess the risk factors for late mortality, loss of sinus rhythm and atrial flutter after the Mustard operation.Background. The Mustard operation provides correction of cyanosis with low surgical risk in transposition of the great vessels. However, right ventricular failure, loss of sinus rhythm, atrial flutter and death are frequent long-term complications.Methods. Records of 534 children who underwent the Mustard operation at a single center since 1962 were reviewed for demographic, anatomic, electrocardiographic and physiologic predictors and outcomes.Results. There were 52 early deaths (9.7%). Survival analysis was undertaken for 478 early survivors with a mean follow-up interval of 11.6 ± 7.2 years. There were 77 late deaths (16.1%), with sudden death (n = 31) the most frequent cause. Survival estimates were 89% at 5 years and 76% at 20 years of age. Risk factors were an earlier date of operation, operative period arrhythmia and an associated ventricular septal defect. Risk (hazard) of late death declined in the first decade, with further peaks in the second decade. Sinus rhythm was present in 77% at 5 years and 40% at 20 years. Loss of sinus rhythm was associated with previous septectomy, postoperative bradycardia and late atrial flutter. Freedom from atrial flutter was 92% at 5 years and 73% at 20 years of age. Risk factors for atrial flutter were the occurrence of perioperative bradyarrhythmia, reoperation and loss of sinus rhythm during follow-up. Risk of atrial flutter demonstrates a late increase.Conclusions. Ongoing loss of sinus rhythm and late peaks in the risk of atrial flutter and death necessitate continued follow-up.(J Am Coll Cardiol 1997;29:194–201)