Knowledge, Technology and Economic Growth during the industrial revolution, in Van ark

anonymous referee for helpful comments and to Steve Nafziger for research assistance

Left ventricular output and aortic blood flow in response to changes in preload and afterload in the preterm piglet heart

Low systemic blood flow occurs in up to 30% of infants born at less than 30 wk gestation. It is associated with increased morbidity and mortality, and current treatments are ineffective in 40% of cases. The aim of this study was to assess the ability of the preterm heart to respond to the acute shifts in preload and afterload that occur at the time of birth. Myocardial and coronary vascular function was assessed using an isolated working heart model in term (115 days) and preterm (92 days) piglets. Cardiac output/kg body wt in preterm hearts was ∼50% lower than that of term hearts (P = 0.001). Pressure development was similar in term and preterm hearts. Elevations in preload increased cardiac output and aortic flow similarly in term and preterm hearts, demonstrating significant preload “reserve”. By contrast, elevations in afterload markedly depressed aortic flow, with a greater proportion of cardiac output being distributed to coronary flow in preterm hearts at high afterloads. The demands of increased workload were associated with greater increases in coronary flow in preterm hearts compared with term hearts. In preterm hearts, exposure to maternal glucocorticoids resulted in increased aortic flow when afterload was below 25 mmHg. These data suggest the preterm heart lacks the functional capacity to acutely adapt to postnatal afterload. To maximize systemic blood flow in preterm infants, treatments limiting afterload, while harnessing significant preload reserve, should be further explored

National Asthma Education and Prevention Program Working Group Report on the Quality of Asthma Care.

The quality of asthma care is the second topic of the National Asthma Education and Prevention Program Task Force Report on the Cost Effectiveness, Quality of Care, and Financing of Asthma Care. This working group recommended an asthma continuous quality improvement model as an appropriate framework for examining the quality of asthma care. This model can be implemented by various organizations and providers of care in a variety of settings. The framework consists of four steps: (1) define the opportunity for improvement, (2) set the asthma quality improvement goals (outcomes), (3) characterize the process of care, and (4) begin the improvement cycle. Several case studies are presented to illustrate the use of this model in various settings, including managed care facilities, emergency departments, teaching hospitals, physician\u27s offices, schools, workplaces, and communities. In addition, the appendix provides an overview of asthma outcome measures in the framework of patient-centered versus organizationally based perspectives

Partial adenosine A1 receptor agonists for cardiovascular therapies

Adenosine, a purine nucleoside, is present in all cells in tightly regulated concentrations. It has many different physiological effects in the whole body and in the heart. Adenosine activates four G protein-coupled receptors A1, A2a, A2b, and A3. Activation of myocardial A1 receptors has been shown to inhibit a variety of myocardial pathologies associated with ischemia and reperfusion injury, including stunning, arrhythmogenesis, coronary and ventricular dysfunction, acute myocardial infarction, apoptosis, and chronic heart failure, implying several options for new cardiovascular therapies for diseases, like angina pectoris, control of cardiac rhythm, ischemic injury during an acute coronary syndrome, or heart failure. However, the main issue of using full A1 receptor agonists in such indications is the broad physiologic spectrum of cardiac and extracardiac effects. Desired A1 receptor-mediated protective and regenerative cardiovascular effects might be counter-regulated by unintended side effects when considering full A1 receptor agonists. These effects can be overcome by partial A1 agonists. Partial A1 agonists can be used to trigger only some of the physiological responses of receptor activation depending on endogenous adenosine levels and on receptor reserve in different tissues. CV-Therapeutics reported the identification of a partial A1 receptor agonist CVT-3619, and recently, another partial A1 receptor agonist VCP28 was published. Both compounds are adenosine derivatives. Adenosine-like A1 receptor agonists often have the drawback of a short half-life and low bioavailability, making them not suitable for chronic oral therapy. We identified the first non-adenosine-like partial A1 receptor agonist(s) with pharmacokinetics optimal for oral once daily treatment and characterized the qualities of the partial character of the A1 receptor agonist(s) in preclinical and clinical studies

Nonpasteurized Dairy Products, Disease Outbreaks, and State Laws—United States, 1993–2006

Most dairy-associated outbreaks occurred in states that permitted sale of these products