Initial Use (initial + use)

Distribution by Scientific Domains

Selected Abstracts

Evolution of physics-based methodology for exploring the conformational energy landscape of proteins

Harold A. Scheraga
Abstract The evolution of our physics-based computational methods for determining protein conformation without the introduction of secondary-structure predictions, homology modeling, threading, or fragment coupling is described. Initial use of a hard-sphere potential captured much of the structural properties of polypeptide chains, and subsequent more refined force fields, together with efficient methods of global optimization provide indications that progress is being made toward an understanding of the interresidue interactions that underlie protein folding. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 28,34, 2002 [source]

Dialyzer reactions in a patient switching from peritoneal dialysis to hemodialysis

Robert C. Yang
Many terms have been used to describe the collection of signs and symptoms triggered by the initial use of dialyzers. These reactions can be divided into Type A (hypersensitivity reactions, with the incidence of 4/100,000) and Type B (nonspecific reactions, incidence 3,5/100). Many different mechanisms have been postulated, including complement activation, pulmonary leukostasis, hypersensitivity to ethylene oxide, interaction between the AN69 membrane and angiotensin-converting enzyme inhibitors, and dialysate contamination. An unusual case of dialyzer reactions is presented here, involving a patient who had to discontinue peritoneal dialysis when she was admitted with fungal peritonitis. Upon initiation of hemodialysis, she experienced dyspnea and burning sensation and demonstrated significant leukopenia, thrombocytopenia, and oxygen desaturation. These reactions persisted despite double-rinsing of the dialyzers and the use of several different dialyzers with synthetic membranes (polysulfone and AN69), and a variety of sterilization methods (electron beam and gamma radiation). In the end, a simple measure was found to be effective in preventing further dialyzer reactions in this fascinating case. [source]


ABSTRACT This paper seeks to chart a concept of historical experience that French Romantic writers first developed to describe their own relationship to historical time: the notion of the "transitional period." At first, the term related strictly to the evolving periodic conception of history, one that required breaks, spaces, or zones of indeterminacy to bracket off periods imagined as organic wholes. These transitions, necessary devices in the new grammar of history, also began to attract interest on their own, conceived either as chaotic but creative times of transformation, or, more often, as slack periods of decadence that possessed no proper style but exhibited hybrid traits. Their real interest, however, lies in their reflexive application to the nineteenth century itself, by writers and historians such as Alfred de Musset, Chateaubriand, Michelet, and Renan, who in their effort to define their own period envisioned the "transitional period" as a passage between more coherent and stable historical formations. This prospective self-definition of the "age of history" from a future standpoint is very revealing; it shows not just the tension between its organic way of apprehending the past and its own self-perception, but it also opens a window on a new and paradoxical experience of time, one in which change is ceaseless and an end in itself. The paper also presents a critique of the way the term "modernity" has functioned, from Baudelaire's initial use to the present, to occlude the experience of transition that the Romantics highlighted. By imposing on the nineteenth-century sense of the transitory a heroic period designation, the term "modernity" denies precisely the reality it describes, and sublimates a widespread temporal malaise into its contrary. The paper concludes that the peculiarly "modern" mania for naming one's period is a function of transitional time, and that the concept coined by the Romantics still governs our contemporary experience. [source]

Congenital Short QT Syndrome and Implantable Cardioverter Defibrillator Treatment:

Inherent Risk for Inappropriate Shock Delivery
Introduction: A congenital short QT interval constitutes a new primary electrical abnormality associated with syncope and/or sudden cardiac death. We report on the initial use of implantable cardioverter defibrillator (ICD) therapy in patients with inherited short QT interval and discuss sensing abnormalities and detection issues. Methods and Results: In five consecutive patients from two unrelated European families who had structurally normal hearts, excessively shortened QT intervals, and a strong positive family history of sudden cardiac death, ICDs were placed for primary and secondary prevention. Mean QT intervals were 252 ± 13 ms (QTc 287 ± 13 ms). Despite normal sensing behavior during intraoperative and postoperative device testing, 3 of 5 patients experienced inappropriate shock therapies for T wave oversensing 30 ± 26 days after implantation. Programming lower sensitivities and decay delays prevented further inappropriate discharges. Conclusion: The congenital short QT syndrome constitutes a new clinical entity with an increased risk for sudden cardiac death. Currently, ICD treatment is the only therapeutic option. In patients with short QT interval and implanted ICD, increased risk for inappropriate therapy is inherent due to the detection of short-coupled and prominent T waves. Careful testing of ICD function and adaptation of sensing levels and decay delays without sacrificing correct arrhythmia detection are essential. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1273-1277, December 2003) [source]

Emerging Insights in the First-Step Use of Antihypertensive Combination Therapy

Keith Norris MD
The blood pressure (BP) goals set by hypertension management guidelines (<140/90 mm Hg in uncomplicated hypertension; <130/80 mm Hg in type 2 diabetes or kidney disease) are not being achieved in a high proportion of patients, partly because monotherapy is insufficient in many patients. In particular, patients with uncontrolled moderate or severe hypertension and/or associated cardiovascular risk factors remain at high risk for cardiovascular events and hypertensive emergency. In recognition of the urgency of treating moderate and severe hypertension, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) advocates the initial use of 2-drug therapies in patients with systolic BP levels >20 mm Hg above goal or diastolic BP level >10 mm Hg above goal. Regimens should usually include a thiazide diuretic and, for patients with diabetes or kidney disease, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Recently, clinical trial data have shown that first-step antihypertensive treatment of moderate and severe hypertension with carefully chosen fixed-dose combinations provides a high rate of BP goal achievement, a simplified dosing regimen, and superior tolerability compared with monotherapy. [source]

Behavioral and Biological Indicators of Impulsivity in the Development of Alcohol Use, Problems, and Disorders

ALCOHOLISM, Issue 8 2010
C.W. Lejuez
Alcohol use disorders (AUDs) are a devastating public health problem. The construct of impulsivity is biologically based and heritable, and its various dimensions are relevant for understanding alcohol use. The goal of the current manuscript is to review recent behavioral and biological research examining various dimensions of impulsivity and their relation to AUDs from risk for initial use through dependence and relapse. Moreover, we also highlight key psychological variables including affective processes as they relate to current use and early indications of alcohol problems, as well as psychopathology, violence, and aggression in relation to AUDs. Each section includes a critical summary and we conclude the review with future directions focused on issues relevant to measurement, causality, and intervention. Throughout the review, we attempt to be as specific as possible about the dimensions of impulsivity being referenced, while attempting to draw parallels and highlighting differences as the existing literature allows. [source]

Three Gorges Project: the largest water conservancy project in the world,

Wang Jiazhu
The Three Gorges Project (TGP) is the largest water conservancy project ever built in China and in the world. Construction of TGP commenced in 1993 and more than half is complete. It is predicted that the project will be put into initial use in 2003, and finished in 2009. This article discusses the project's advantages and some of the challenges faced, including technical, environmental and resettlement issues. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Do Off-Label Drug Practices Argue Against FDA Efficacy Requirements?

A Critical Analysis of Physicians' Argumentation for Initial Efficacy Requirements
The amended Food, Drug and Cosmetics Act requires efficacy certification for a drug's initial uses ("on-label"), but does not require certification before physicians may prescribe the drug for subsequent uses ("off-label"). Does it make sense to require FDA efficacy certification for new drugs but not for new uses of old drugs? Using a sequential online survey, we carried on a "virtual conversation" with some 500 physicians. The survey asked whether efficacy requirements should be imposed on off-label uses; almost all physicians said no. It asked whether the efficacy requirements for initial uses should be dropped, and most physicians said no. We then asked respondents whether opposing efficacy requirements in one case but not the other involved an inconsistency. In response, we received hundreds of written commentaries. We organize and discuss these commentaries with an eye to understanding how the medical market certifies off-label drug uses and how this compares to FDA certification. Does off-label medicine use suggest that efficacy requirements should be placed on new uses of old drugs? Does it suggest that efficacy requirements on new drugs should be lifted? We explore these questions, and ask whether the response of many of the doctors exhibits the familiar behavior bias toward the status quo. [source]