Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aortic regurgitation and normal left ventricular performance

BACKGROUND: Optimal criteria for valve replacement are unclear in asymptomatic/minimally symptomatic patients with aortic regurgitation (AR) and normal left ventricular (LV) performance at rest. Moreover, previous studies have not assessed the prognostic capacity of load-adjusted LV performance ("contractility") variables, which may be fundamentally related to clinical state. Therefore, 18 years ago, we set out to test prospectively the hypothesis that objective noninvasive measures of LV size and performance and, specifically, of load-adjusted variables, assessed at rest and during exercise (ex), could predict the development of currently accepted indications for operation for AR. METHODS AND RESULTS: Clinical variables and measures of LV size, performance, and end-systolic wall stress (ESS) were assessed annually in 104 patients by radionuclide cineangiography at rest and maximal ex and by echocardiography at rest; ESS was derived during ex. During an average 7.3-year follow-up among patients who had not been operated on, 39 of 104 patients either died suddenly (n = 4) or developed operable symptoms only (n = 22) or subnormal LV performance with or without symptoms (n = 13) (progression rate=6.2%/y). By multivariate Cox model analysis, change (delta) in LV ejection fraction (EF) from rest to ex, normalized for deltaESS from rest to ex (deltaLVEF-deltaESS index), was the strongest predictor of progression to any end point or to sudden cardiac death alone. Unadjusted deltaLVEF was almost as efficient. Symptom status modified prediction on the basis of the deltaLVEF-deltaESS index. The population tercile at highest risk by deltaLVEF-deltaESS progressed to end points at a rate of 13.3%/y, and the lowest-risk tercile progressed at 1.8%/y. CONCLUSIONS: Currently accepted symptom and LV performance indications for valve replacement, as well as sudden cardiac death, can be predicted in asymptomatic/minimally symptomatic patients with AR by load-adjusted deltaLVEF-deltaESS index, which includes data obtained during exercise.     

Plasma-derived proteins in airway defence, disease and repair of epithelial injury

One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.     

Microvascular transplantation in the salvage of lower extremity trauma in the elderly

In the cadaver of an 86 year old man the inferior segment of the azygos vein could not be found. Furthermore, a normally developed hemiazygos vein drained the right and left intercostal veins from T 10 to T 6. This vessel finally curved towards the right to reach the superior vena cava after having drained the right superior intercostal veins. The left superior intercostal vein ended in a short vessel draining into the left brachiocephalic vein. This condition may be represented in a standard chest radiograph by the so-called "aortic nipple". Agenesis of the azygos vein, suspected because of the presence of this radiological sign, should be confirmed in the living by means of computerized tomography. This can clarify the anatomy of the mediastinal vessels precisely. Embryological pattern of the azygos system accounting for its possible defects is discussed.     

Clinical trial designs--made to order

At times, clinical trial design presents difficult problems for the consulting statistician. The nature of the disease under study or the inadequacies of standard methodology often suggest alternative strategies for the development of useful clinical trial designs. This paper examines two case of novel clinical trial designs that are "made-to-order" for the problem at hand. Both address disease-specific issues. The first case considers the use of adaptive allocation of treatments to patients in a trial in major depressive disorder. The second case reviews the design of a novel efficacy parameter in advanced pancreatic cancer.     

Isotype-specific antibody responses to foot-and-mouth disease virus in sera and secretions of "carrier' and "non-carrier' cattle

Isotype-specific antibody responses to foot-and-mouth disease virus (FMDV) were measured in the sera and upper respiratory tract secretions of vaccinated and susceptible cattle challenged with FMDV by direct contact or by intranasal inoculation. A comparison was made between cattle that eliminated FMDV and those that developed and maintained a persistent infection. Serological and mucosal antibody responses were detected in all animals after challenge. IgA and IgM were detected before the development of IgG1 and IgG2 responses. IgM was not detected in vaccinated cattle. Challenge with FMDV elicited a prolonged biphasic secretory antibody response in FMDV "carrier' animals only. The response was detected as FMDV-specific IgA in both mucosal secretions and serum samples, which gained statistical significance (P < 0.05) by 5 weeks after challenge. This observation could represent the basis of a test to differentiate vaccinated and/or recovered convalescent cattle from FMDV "carriers'.     

Comparison of paper-and-pencil versus Web administration of the Youth Risk Behavior Survey (YRBS): Participation,data quality,and perceived privacy and anonymity

The Youth Risk Behavior Surveillance System (YRBSS) monitors priority health-risk behaviors among US high school students. To better understand the ramifications of changing the YRBSS from paper-and-pencil to Web administration, in 2008 the Centers for Disease Control and Prevention conducted a study comparing these two modes of administration. Eighty-five schools in 15 states agreed to participate in the study. Within each participating school, four classrooms of students in grades 9 or 10 were randomly assigned to complete the Youth Risk Behavior Survey questionnaire in one of four conditions (in-class paper-and-pencil, in-class Web without programmed skip patterns, in-class Web with programmed skip patterns, and “on your own” Web without programmed skip patterns). Findings included less missing data for the paper-and-pencil condition (1.5% vs. 5.3%, 4.4%, 6.4%; p < .001), less perceived privacy and anonymity among respondents for the in-class Web conditions, and a lower response rate for the “on your own” Web condition than for in-class administration by either mode (28.0% vs. 91.2%, 90.1%, 91.4%; p < .001). Although Web administration might be useful for some surveys, these findings do not favor the use of a Web survey for the YRBSS.     

Linear-Time Recognition of Helly Circular-Arc Models and Graphs

A circular-arc model ℳ is a circle C together with a collection A\mathcal{A} of arcs of C. If A\mathcal{A} satisfies the Helly Property then ℳ is a Helly circular-arc model. A (Helly) circular-arc graph is the intersection graph of a (Helly) circular-arc model. Circular-arc graphs and their subclasses have been the object of a great deal of attention in the literature. Linear-time recognition algorithms have been described both for the general class and for some of its subclasses. However, for Helly circular-arc graphs, the best recognition algorithm is that by Gavril, whose complexity is O(n ³). In this article, we describe different characterizations for Helly circular-arc graphs, including a characterization by forbidden induced subgraphs for the class. The characterizations lead to a linear-time recognition algorithm for recognizing graphs of this class. The algorithm also produces certificates for a negative answer, by exhibiting a forbidden subgraph of it, within this same bound.     

Introducing the IA-64 architecture

Microprocessors continue on the relentless path to provide more performance. Every new innovation in computing-distributed computing on the Internet, data mining, Java programming, and multimedia data streams-requires more cycles and computing power. Even traditional applications such as databases and numerically intensive codes present increasing problem sizes that drive demand for higher performance. Design innovations, compiler technology, manufacturing process improvements, and integrated circuit advances have been driving exponential performance increases in microprocessors. To continue this growth in the future, Hewlett Packard and Intel architects examined barriers in contemporary designs and found that instruction-level parallelism (ILP) can be exploited for further performance increases. This article examines the motivation, operation, and benefits of the major features of IA-64. Intel's IA-64 manual provides a complete specification of the IA-64 architecture     

A spreadsheet approach to facilitate visualization of uncertainty in information

Information uncertainty is inherent in many problems and is often subtle and complicated to understand. Although visualization is a powerful means for exploring and understanding information, information uncertainty visualization is ad hoc and not widespread. This paper identifies two main barriers to the uptake of information uncertainty visualization: firstly, the difficulty of modeling and propagating the uncertainty information; and secondly, the difficulty of mapping uncertainty to visual elements. To overcome these barriers, we extend the spreadsheet paradigm to encapsulate uncertainty details within cells. This creates an inherent awareness of the uncertainty associated with each variable. The spreadsheet can hide the uncertainty details, enabling the user to think simply in terms of variables. Furthermore, the system can aid with automated propagation of uncertainty information, since it is intrinsically aware of the uncertainty. The system also enables mapping the encapsulated uncertainty to visual elements via the formula language and a visualization sheet. Support for such low-level visual mapping provides flexibility to explore new techniques for information uncertainty visualization.