Genetic testing for the long QT syndrome: who and why? Insights for clinical management

This article deals with a specifi c issue of growing importance for cardiologists or internists who happen to have to take care of a patient affected by the congenital long QT syndrome (LQTS), namely when to consider to request a genetic test. The focus is on who are the patients for whom genetic screening should be requested and why. One often ignored issue is also discussed, the potentially very serious consequences – for the patient and also for the doctor – of omitting genetic screening. The bottom line is that genetic screening for LQTS can no longer be regarded as a research tool but is an integral part of current medical management of this life-threatening but highly treatable disorder

Rube Stories and Paradigmatic Crimes as Narrative Modulators at Thresholds of Cultural Change

This essay investigates two species of a larger genus of narrative (“narrative modulators”) characterized by its function as a sort of compromise formation addressing recurrent anxieties and tensions at major thresholds of cultural change. One of these is a story type linked with cinema’s early reception: that of the “credulous spectator,” figured in early film and film lore as the country bumpkin or “rube” who, misperceiving the projected image as real, runs from the oncoming train or from the wet of onscreen waves or tries to enter the story; I extend this type beyond cinema to include precinematic literary examples. I’ve coined the term “paradigmatic crimes” to describe stories of criminal acts used to address pressing cultural concerns at given historical junctures as a second type of “narrative modulator.” As with “rube stories,” what unifies “paradigmatic crimes” as a story type is their specific function as “narrative modulators” in moments of cultural change. My hypothesis is that functionally similar stories appear at structurally comparable thresholds of media change in various cultures at various times, and that the similarities are to be explained mainly morphologically (i.e. mainly at the abstract level of their capacity to modulate cultural change).This essay investigates two species of a larger genus of narrative (“narrative modulators”) characterized by its function as a sort of compromise formation addressing recurrent anxieties and tensions at major thresholds of cultural change. One of these is a story type linked with cinema’s early reception: that of the “credulous spectator,” figured in early film and film lore as the country bumpkin or “rube” who, misperceiving the projected image as real, runs from the oncoming train or from the wet of onscreen waves or tries to enter the story; I extend this type beyond cinema to include precinematic literary examples. I’ve coined the term “paradigmatic crimes” to describe stories of criminal acts used to address pressing cultural concerns at given historical junctures as a second type of “narrative modulator.” As with “rube stories,” what unifies “paradigmatic crimes” as a story type is their specific function as “narrative modulators” in moments of cultural change. My hypothesis is that functionally similar stories appear at structurally comparable thresholds of media change in various cultures at various times, and that the similarities are to be explained mainly morphologically (i.e. mainly at the abstract level of their capacity to modulate cultural change)

Money versus Credit Rationing: Evidence for the National Banking Era, 1880-1914

In this paper we examine the evidence for two competing views of how monetary and financial disturbances influenced the real economy during the national banking era, 1880-1914. According to the monetarist view, monetary disturbances affected the real economy through changes on the liability side of the banking system's balance sheet independent of the composition of bank portfolios. According to the credit rationing view, equilibrium credit rationing in a world of asymmetric information can explain short-run fluctuations in real output. Using structural VARs we incorporate monetary variables in credit models and credit variables in monetarist models, with inconclusive results. To resolve this ambiguity, we invoke the institutional features of the national banking era. Most of the variation in bank loans is accounted for by loans secured by stock, which in turn reflect volatility in the stock market. When account is taken of the stock market, the influence of credit in the VAR model is greatly reduced, while the influence of money remains robust. The breakdown of the composition of bank loans into stock market loans (traded in open asset markets) and other business loans (a possible setting for credit rationing) reveals that other business loans remained remarkably stable over the business cycle.

The long QT syndrome

Major progress has taken place, and at a very rapid pace, in the understanding of the congenital long QT syndrome (LQTS). This has been the direct consequence of the identification of several of the genes responsible for LQTS and of the studies that have followed, at both basic and clinical levels. A key issue is represented by the fact that all LQTS genes identified so far encode for ionic channels involved in the control of repolarization. The expression studies of the mutated genes have allowed identification of the specific electrophysiologic consequences of the specific mutations and have demonstrated alterations in the NA+ and in K+ currents sufficient to explain the prolongation of action potential duration and, hence, of the QT interval. Ongoing studies in the selected LQTS patients, for whom the specific mutations are known, are allowing a unique understanding of the complex genotype-phenotype correlation. These studies indicate the existence of what appear to be gene-specific patterns in many clinically important features such as the response to therapeutic interventions, the response to increases in heart rate, and in the factors that precipitate the life-threatening arrhythmias typical of this intriguing disease

U.S. Energy Scenarios for the 21st Century

Discusses three divergent paths for U.S. energy supply and use from 2000 through 2035, and the effect of climate policy on the three scenarios

Electron Self Energy for Higher Excited S Levels

A nonperturbative numerical evaluation of the one-photon electron self energy for the 3S and 4S states with charge numbers Z=1 to 5 is described. The numerical results are in agreement with known terms in the expansion of the self energy in powers of Zalpha.Comment: 3 pages, RevTeX, to appear in Phys. Rev.

Managing Complex Scheduling Problems with Dynamic and Hybrid Constraints.

The task of scheduling can often be a difficult one because of the inherent complexity of real-world problems. In the field of Artificial Intelligence, many representations and algorithms have been developed to automate the scheduling process. Many state of the art scheduling systems deal with this complexity by making assumptions that simplify the algorithms, but in doing so, miss some opportunities to improve performance. Scheduling problems are temporal in nature, and so they often contain constraints that change over time. Many scheduling systems assume that the problems they are solving are all independent, and so they ignore the similarities between subsequent sets of scheduling constraints. Additionally, scheduling problems often contain a mixture of finite-domain and temporal constraints. Many of the systems that can solve problems of this type do so by creating finite-domain variables to represent the constraints, but then ignore the distinction between the different types of variables when searching for a solution. In this dissertation, I identify opportunities to improve performance by exploiting structure where it has previously been overlooked. Following this approach, I develop a set of techniques that apply to a wide variety of situations that can arise in real-world scheduling problems. First, I consider dynamic scheduling problems with constraints that change over time. To address such problems, I introduce a new representation called the Dynamic Disjunctive Temporal Problem, along with several techniques to improve both efficiency and stability when solving one. Second, I consider scheduling problems in which a mixture of finite-domain and temporal variables can interact through hybrid constraints. I introduce the Hybrid Scheduling Problem to represent such problems, and I present a set of techniques that capitalize on the distinction between variable types to improve efficiency across the problem space. Finally, I conclude by proposing several ways that the dynamic and hybrid representations and techniques can be combined. To compare many of the techniques presented throughout this dissertation in the context of structured, real-world problems, I use them to solve scheduling problems based on actual air traffic control constraints recorded from the Dallas/Fort Worth International Airport.Ph.D.Computer Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/57625/2/pschwart_1.pd

Congenital Short QT Syndrome

The Short QT Syndrome is a recently described new genetic disorder, characterized by abnormally short QT interval, paroxysmal atrial fibrillation and life threatening ventricular arrhythmias. This autosomal dominant syndrome can afflict infants, children, or young adults; often a remarkable family background of cardiac sudden death is elucidated. At electrophysiological study, short atrial and ventricular refractory periods are found, with atrial fibrillation and polymorphic ventricular tachycardia easily induced by programmed electrical stimulation. Gain of function mutations in three genes encoding K+ channels have been identified, explaining the abbreviated repolarization seen in this condition: KCNH2 for Ikr (SQT1), KCNQ1 for Iks (SQT2) and KCNJ2 for Ik1 (SQT3). The currently suggested therapeutic strategy is an ICD implantation, although many concerns exist for asymptomatic patients, especially in pediatric age. Pharmacological treatment is still under evaluation; quinidine has shown to prolong QT and reduce the inducibility of ventricular arrhythmias, but awaits additional confirmatory clinical data