Diabetic cardiomyopathy is a disease process in which diabetes produces a direct and continuous myocardial insult even in the absence of ischemic, hypertensive or valvular disease. The β-blocking agents bisoprolol, c...Diabetic cardiomyopathy is a disease process in which diabetes produces a direct and continuous myocardial insult even in the absence of ischemic, hypertensive or valvular disease. The β-blocking agents bisoprolol, carvedilol and metoprolol have been shown in large-scale randomized controlled trials to reduce heart failure mortality. In this review, we summarize the results of our studies investigating the effects of β-blocking agents on cardiac function and metabolism in diabetic heart failure, and the complex inter-related mechanisms involved. Metoprolol inhibits fatty acid oxidation at the mitochondrial level but does not prevent lipotoxicity; its benefi cial effects are more likely to be due to prosurvival effects of chronic treatment. These studies have expanded our understanding of the range of effects produced by β-adrenergic blockade and showhow interconnected the signaling pathways of function and metabolism are in the heart. Although our initial hypothesis that inhibition of fatty acid oxidation would be a key mechanism of action was disproved, unexpected results led us to some intriguing regulatory mechanisms of cardiac metabolism. The fi rst was upstream stimulatory factor-2-mediated repression of transcriptional master regulator PGC-1α, most likely occurring as a consequence of the improved function; it is unclear whether this effect is unique to β-blockers, although repression of carnitine palmitoyltransferase (CPT)-1 has not been reported with other drugs which improve function. The second was the identif ication of a range of covalent modifications which can regulate CPT-1 directly, mediated by a signalome at the level of the mitochondria. We also identif ied an important interaction between β-adrenergic signaling and caveolins, which may be a key mechanism of action of β-adrenergic blockade. Our experience with this labyrinthine signaling web illustrates that initial hypotheses and anticipat-ed directions do not have to be right in order to open up meaningful directions or reveal new information.展开更多
Computerized geological models are the basis of modern mine design,planning and production.A sound,validated geological model is essential to the success of a min- ing project.However,due to the complexity of geology ...Computerized geological models are the basis of modern mine design,planning and production.A sound,validated geological model is essential to the success of a min- ing project.However,due to the complexity of geology surrounding deposits,geological models inherit uncertainty,or error.This geological uncertainty may significantly affect the risk profile of a mining project during its design and operational phases.Methodologies for quantifying geological uncertainty and risk have been developed by CRC Mining and the University of Queensland,Australia and successfully applied to case studies.This paper discussed the implications of geological uncertainty and risk to a coal mining project,and presents advances for quantifying geological/geotechnical uncertainty and risk.A case study is presented to demonstrate the application of the technology developed.展开更多
Medical education is associated with significant costs[1].These costs have led to a growing interest in how to deliver high quality or high quantity education on a limited budget.This in turn has led to an interest in...Medical education is associated with significant costs[1].These costs have led to a growing interest in how to deliver high quality or high quantity education on a limited budget.This in turn has led to an interest in how best to measure quantity,quality and cost and how to track these variables over time.The ultimate aim of the interest in cost and value in medical education is to展开更多
Dear Editor： In the UK and in many other countries throughout the world, medical students are paying for their med- ical education~. They might be paying the entire fee or a sizable proportion of it - but many of the...Dear Editor： In the UK and in many other countries throughout the world, medical students are paying for their med- ical education~. They might be paying the entire fee or a sizable proportion of it - but many of them are increasingly making a contribution.展开更多
Dear Editor,Technology enhanced learning has made many advances in the field of medical education over the past twenty years.There has been the advent of e-learning,simulation,and multimedia resources to name but a fe...Dear Editor,Technology enhanced learning has made many advances in the field of medical education over the past twenty years.There has been the advent of e-learning,simulation,and multimedia resources to name but a few＂.Many of the advances made in technology enhanced learning,however,have followed traditional technologies in media and education.Thus,展开更多
Dear Editor： Medical education is associated with significant costs. Those who are responsible for the delivery of medical education must continually make deci- sions that have financial consequences. Sometimes deci...Dear Editor： Medical education is associated with significant costs. Those who are responsible for the delivery of medical education must continually make deci- sions that have financial consequences. Sometimes decisions are to invest in a new product or service, sometimes to disinvest. Sometimes decisions involve the educator realising that they should switch from one provider of medical education to another, or from one product to another. Consciously or unconsciously these decisions are inevitably made on value-educators want to maximise the outcomes from medical educa- tion or to minimise costs. But decisions to change inevitably involve cost in themselves-these are called switching costs （or sometimes switching barriers）.展开更多
Community based interventions increase knowledge scores and also have an impact of sexual behaviours with regard to HIV.However the problem remains as to how best to scale up these interventions and how best to overco...Community based interventions increase knowledge scores and also have an impact of sexual behaviours with regard to HIV.However the problem remains as to how best to scale up these interventions and how best to overcome real or perceived barriers to their uptake.Community based interventions have multiple components and some will be more difficult to widen out than others.Those that involve face to face or one to one sessions will be most expensive and so most difficult to scale up.If some interventions can be implemented by means of custom computerized risk reduction programmes,then roll out on a large scale should be less problematic.展开更多
Syncope belongs to the transient loss of consciousness(TLOC), characterized by a rapid onset, short duration, and spontaneous complete recovery. It is common in children and adolescents, accounting for 1% to 2% of eme...Syncope belongs to the transient loss of consciousness(TLOC), characterized by a rapid onset, short duration, and spontaneous complete recovery. It is common in children and adolescents, accounting for 1% to 2% of emergency department visits.Recurrent syncope can seriously affect children's physical and mental health, learning ability and quality of life and sometimes cardiac syncope even poses a risk of sudden death. The present guideline for the diagnosis and treatment of syncope in children and adolescents was developed for guiding a better clinical management of pediatric syncope. Based on the globally recent development and the evidence-based data in China, 2018 Chinese Pediatric Cardiology Society(CPCS) guideline for diagnosis and treatment of syncope in children and adolescents was jointly prepared by the Pediatric Cardiology Society, Chinese Pediatric Society, Chinese Medical Association(CMA)/Committee on Pediatric Syncope, Pediatricians Branch, Chinese Medical Doctor Association(CMDA)/Committee on Pediatric Cardiology, Chinese College of Cardiovascular Physicians, Chinese Medical Doctor Association(CMDA)/Pediatric Cardiology Society, Beijing Pediatric Society, Beijing Medical Association(BMA). The present guideline includes the underlying diseases of syncope in children and adolescents, the diagnostic procedures, methodology and clinical significance of standing test and headup tilt test, the clinical diagnosis vasovagal syncope, postural orthostatic tachycardia syndrome, orthostatic hypotension and orthostatic hypertension, and the treatment of syncope as well as follow-up.展开更多
基金Supported by The Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada
文摘Diabetic cardiomyopathy is a disease process in which diabetes produces a direct and continuous myocardial insult even in the absence of ischemic, hypertensive or valvular disease. The β-blocking agents bisoprolol, carvedilol and metoprolol have been shown in large-scale randomized controlled trials to reduce heart failure mortality. In this review, we summarize the results of our studies investigating the effects of β-blocking agents on cardiac function and metabolism in diabetic heart failure, and the complex inter-related mechanisms involved. Metoprolol inhibits fatty acid oxidation at the mitochondrial level but does not prevent lipotoxicity; its benefi cial effects are more likely to be due to prosurvival effects of chronic treatment. These studies have expanded our understanding of the range of effects produced by β-adrenergic blockade and showhow interconnected the signaling pathways of function and metabolism are in the heart. Although our initial hypothesis that inhibition of fatty acid oxidation would be a key mechanism of action was disproved, unexpected results led us to some intriguing regulatory mechanisms of cardiac metabolism. The fi rst was upstream stimulatory factor-2-mediated repression of transcriptional master regulator PGC-1α, most likely occurring as a consequence of the improved function; it is unclear whether this effect is unique to β-blockers, although repression of carnitine palmitoyltransferase (CPT)-1 has not been reported with other drugs which improve function. The second was the identif ication of a range of covalent modifications which can regulate CPT-1 directly, mediated by a signalome at the level of the mitochondria. We also identif ied an important interaction between β-adrenergic signaling and caveolins, which may be a key mechanism of action of β-adrenergic blockade. Our experience with this labyrinthine signaling web illustrates that initial hypotheses and anticipat-ed directions do not have to be right in order to open up meaningful directions or reveal new information.
文摘Computerized geological models are the basis of modern mine design,planning and production.A sound,validated geological model is essential to the success of a min- ing project.However,due to the complexity of geology surrounding deposits,geological models inherit uncertainty,or error.This geological uncertainty may significantly affect the risk profile of a mining project during its design and operational phases.Methodologies for quantifying geological uncertainty and risk have been developed by CRC Mining and the University of Queensland,Australia and successfully applied to case studies.This paper discussed the implications of geological uncertainty and risk to a coal mining project,and presents advances for quantifying geological/geotechnical uncertainty and risk.A case study is presented to demonstrate the application of the technology developed.
文摘Medical education is associated with significant costs[1].These costs have led to a growing interest in how to deliver high quality or high quantity education on a limited budget.This in turn has led to an interest in how best to measure quantity,quality and cost and how to track these variables over time.The ultimate aim of the interest in cost and value in medical education is to
文摘Dear Editor： In the UK and in many other countries throughout the world, medical students are paying for their med- ical education~. They might be paying the entire fee or a sizable proportion of it - but many of them are increasingly making a contribution.
文摘Dear Editor,Technology enhanced learning has made many advances in the field of medical education over the past twenty years.There has been the advent of e-learning,simulation,and multimedia resources to name but a few＂.Many of the advances made in technology enhanced learning,however,have followed traditional technologies in media and education.Thus,
文摘Dear Editor： Medical education is associated with significant costs. Those who are responsible for the delivery of medical education must continually make deci- sions that have financial consequences. Sometimes decisions are to invest in a new product or service, sometimes to disinvest. Sometimes decisions involve the educator realising that they should switch from one provider of medical education to another, or from one product to another. Consciously or unconsciously these decisions are inevitably made on value-educators want to maximise the outcomes from medical educa- tion or to minimise costs. But decisions to change inevitably involve cost in themselves-these are called switching costs （or sometimes switching barriers）.
文摘Community based interventions increase knowledge scores and also have an impact of sexual behaviours with regard to HIV.However the problem remains as to how best to scale up these interventions and how best to overcome real or perceived barriers to their uptake.Community based interventions have multiple components and some will be more difficult to widen out than others.Those that involve face to face or one to one sessions will be most expensive and so most difficult to scale up.If some interventions can be implemented by means of custom computerized risk reduction programmes,then roll out on a large scale should be less problematic.
文摘Syncope belongs to the transient loss of consciousness(TLOC), characterized by a rapid onset, short duration, and spontaneous complete recovery. It is common in children and adolescents, accounting for 1% to 2% of emergency department visits.Recurrent syncope can seriously affect children's physical and mental health, learning ability and quality of life and sometimes cardiac syncope even poses a risk of sudden death. The present guideline for the diagnosis and treatment of syncope in children and adolescents was developed for guiding a better clinical management of pediatric syncope. Based on the globally recent development and the evidence-based data in China, 2018 Chinese Pediatric Cardiology Society(CPCS) guideline for diagnosis and treatment of syncope in children and adolescents was jointly prepared by the Pediatric Cardiology Society, Chinese Pediatric Society, Chinese Medical Association(CMA)/Committee on Pediatric Syncope, Pediatricians Branch, Chinese Medical Doctor Association(CMDA)/Committee on Pediatric Cardiology, Chinese College of Cardiovascular Physicians, Chinese Medical Doctor Association(CMDA)/Pediatric Cardiology Society, Beijing Pediatric Society, Beijing Medical Association(BMA). The present guideline includes the underlying diseases of syncope in children and adolescents, the diagnostic procedures, methodology and clinical significance of standing test and headup tilt test, the clinical diagnosis vasovagal syncope, postural orthostatic tachycardia syndrome, orthostatic hypotension and orthostatic hypertension, and the treatment of syncope as well as follow-up.
