An extensive array of measurements extending back to the mid-19th century was used to investigate large-scale changes in precipitation over Northern Hemisphere land areas. Significant increases in mid-latitude precipitation and concurrent decreases in low-latitude precipitation have occurred over the last 30 to 40 years. Although these large-scale trends are consistent with general circulation model projections of precipitation changes associated with doubled concentrations of atmospheric carbon dioxide, they should be viewed as defining large-scale natural climatic variability. Additional work to refine regional variations and address potential network inhomogeneitics is needed. This study attempts to show secular precipitation fluctuations over hemispheric and continental-scale areas of the Northern Hemisphere.

BACKGROUND Small-scale clinical investigations have demonstrated that single doses of beta-blocking agents can improve left ventricular function in heart failure from idiopathic dilated cardiomyopathy (IDC). The purpose of this multicenter clinical trial was to determine the dose-effect characteristics of beta-blockade in a heart failure population that includes ischemic dilated cardiomyopathy (ISCD). METHODS AND RESULTS Bucindolol is a nonselective beta-blocking agent with mild vasodilatory properties. One hundred forty-one subjects with class II or III heart failure, left ventricular ejection fraction (LVEF) < or = 0.40, and background therapy of angiotensin-converting enzyme inhibitors, digoxin, and diuretics were given an initial challenge dose of bucindolol 12.5 mg. One hundred thirty-nine subjects (99 with IDC, 40 with ISCDC) tolerated challenge and were randomized to treatment with placebo or bucindolol 12.5 mg/d (low dose), 50 mg/d (medium dose), or 200 mg/d (high dose). At the end of 12 weeks, left ventricular function and other parameters were measured and compared with baseline values. There was a dose-related improvement in left ventricular function in bucindolol-treated subjects. In the high-dose bucindolol group, radionuclide-measured LVEF improved by 7.8 EF units (%) compared with 1.8 units in the placebo group (P < .05), and compared with the placebo group, a greater percentage of subjects had an increase in LVEF by > or = 5 units. In contrast, all three bucindolol doses prevented deterioration of myocardial function as defined by an LVEF decline of > or = 5 units. CONCLUSIONS In heart failure from systolic dysfunction, beta-blockade with bucindolol produces a dose-related improvement in and prevents deterioration of left ventricular function.

We describe a quantitative histological study of 34 breast biopsies using a marker for human macrophages, the monoclonal antibody EBM/11. Seventeen of the biopsies were of malignant tumours. Both benign and malignant breast tissue contained large numbers of macrophages with significantly higher numbers occurring in the malignant group. An analysis was made of macrophage counts according to stage, grade and prognostic index of the malignant tumours. There was no correlation between macrophage numbers and any of these parameters in malignant breast tumours. We discuss the possible reasons why some earlier studies (using other markers such as lysozyme), have shown an apparently insignificant number of intratumoral macrophages. Images Figure 1 Figure 2

Despite some issues that still need to be resolved, the C(3) Instrument proved to be a reliable and valid tool that characterizes a medical school's hidden curriculum with respect to patient-centered care. It can be used to guide educational interventions by addressing the context that exists around formal teaching activities. It also makes possible the study of hidden curricula across multiple medical schools. Further research on the hidden curriculum should be aimed at developing a greater understanding of the dynamics between formal teaching activities and school culture.

Transition state analogues of PNP, the Immucillins and DADMe-Immucillins, were designed to match transition state features of bovine and human PNPs, respectively. A third generation of inhibitors has been designed that contain an acyclic iminoalcohol to replace the cyclic mimic of the ribooxacarbenium ion at the transition states of PNPs. The best third generation inhibitor is equivalent to the best inhibitors found in the previous transition state analogues.

No abstract

No abstract

No abstract