Families or Unrelated: The Evolving Debate in Genetic Association Studies

To help uncover the genetic determinants of complex disease, a scientist often designs an association study using either unrelated subjects or family members within pedigrees. But which of these two subject recruitment paradigms is preferable? This editorial addresses the debate over the relative merits of family- and population-based genetic association studies. We begin by briefly recounting the evolution of genetic epidemiology and the rich crossroads of statistics and genetics. We then detail the arguments for the two aforementioned paradigms in recent and current applications. Finally, we speculate on how the debate may progress with the emergence of next-generation sequencing technologies

Comment on “Ascertainment adjustment in complex diseases”

No AbstractPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34935/1/10197_ftp.pd

Autocatalytic plume pinch-off

A localized source of buoyancy flux in a non-reactive fluid medium creates a plume. The flux can be provided by either heat, a compositional difference between the fluid comprising the plume and its surroundings, or a combination of both. For autocatalytic plumes produced by the iodate-arsenous acid reaction, however, buoyancy is produced along the entire reacting interface between the plume and its surroundings. Buoyancy production at the moving interface drives fluid motion, which in turn generates flow that advects the reaction front. As a consequence of this interplay between fluid flow and chemical reaction, autocatalytic plumes exhibit a rich dynamics during their ascent through the reactant medium. One of the more interesting dynamical features is the production of an accelerating vortical plume head that in certain cases pinches-off and detaches from the upwelling conduit. After pinch-off, a new plume head forms in the conduit below, and this can lead to multiple generations of plume heads for a single plume initiation. We investigated the pinch-off process using both experimentation and simulation. Experiments were performed using various concentrations of glycerol, in which it was found that repeated pinch-off occurs exclusively in a specific concentration range. Autocatalytic plume simulations revealed that pinch-off is triggered by the appearance of accelerating flow in the plume conduit.Comment: 10 figures. Accepted for publication in Phys Rev E. See also http://www.physics.utoronto.ca/nonlinear/papers_chemwave.htm

Exotic torus manifolds and equivariant smooth structures on quasitoric manifolds

In 2006 Masuda and Suh asked if two compact non-singular toric varieties having isomorphic cohomology rings are homeomorphic. In the first part of this paper we discuss this question for topological generalizations of toric varieties, so-called torus manifolds. For example we show that there are homotopy equivalent torus manifolds which are not homeomorphic. Moreover, we characterize those groups which appear as the fundamental groups of locally standard torus manifolds. In the second part we give a classification of quasitoric manifolds and certain six-dimensional torus manifolds up to equivariant diffeomorphism. In the third part we enumerate the number of conjugacy classes of tori in the diffeomorphism group of torus manifolds. For torus manifolds of dimension greater than six there are always infinitely many conjugacy classes. We give examples which show that this does not hold for six-dimensional torus manifolds.Comment: 21 pages, 2 figures, results about quasitoric manifolds adde

Strong partnerships make good partners: Insights about physician-hospital relationships from a study of physician executives

While physicians are likely to respond favorably in concept to hospital-based disease management and other clinical programs, they are less likely to accept their structural and functional characteristics. Because of their role at the hospital-physician interface, hospital physician executives are often tasked with implementing such programs. Given the challenges involved, a deeper understanding of the role of these executives in building the hospital-physician relationship will therefore be an important contribution. To this end, we surveyed senior physician executives at hospitals and health systems (n = 326), to assess their view of the hospital-physician relationship at their institutions, focusing especially on the role of medical staff cohesion. This article presents several of our key findings, in particular that (1) many physician executives identified their medical staff as having relatively low cohesion and (2) the perceived level of medical staff cohesion correlated strongly with the level of physician support for organizational priorities, the degree of constructive physician involvement, and success in improving the physician-hospital relationship. In light of these findings, we conclude by offering concrete recommendations for physician executives and others seeking to build medical staff cohesion in the service of clinical improvement

Use of P wave configuration during atrial tachycardia to predict site of origin

Objectives.This study sought to construct an algorithm to differentiate left atrial from right atrial tachycardia foci on the basis of surface electrocardiograms (ECGs).Background.Atrial tachycardia is an uncommon form of supraventricular tachycardia, often resistant to drug therapy.Methods.A total of 31 consecutive patients with atrial tachycardia due to either abnormal automaticity or triggered rhythm underwent detailed atrial endocardial mapping and successful radiofrequency catheter ablation of a single atrial focus. P wave configuration was analyzed from 12-lead ECGs during tachycardia during either spontaneous or pharmacologically induced atrioventricular block. P waves inscribed above the isoelectric line (TP interval) were classified as positive, below as negative, above and below (or conversely, below and above) as biphasic and flat P waves as isoelectric (0). In 17 patients the tachycardia was located in the right atrium: crista terminalis (n = 4); right atrial appendage (n = 4); lateral wall (n = 4); posteroinferior right atrium (n = 3); tricuspid annulus (n = 1); and near the coronary sinus (n = 1). In 14 patients, atrial tachycardia was located in the left atrium: at the entrance of the right (n = 6) or left (n = 4) superior pulmonary veins; left inferior pulmonary vein (n = 1); inferior left atrium (n = 1); base of left atrial appendage (n = 1); and high lateral left atrium (n = 1).Results.There were no differences in P wave vectors between sites at the right atrial lateral wall versus the right atrial appendage or between sites at the entrance of right versus left superior pulmonary veins. However, analysis of P wave configuration showed that leads aVL and V1were most helpful in distinguishing right atrial from left atrial foci. The sensitivity and specificity of using a positive or biphasic P wave in lead aVL to predict a right atrial focus was 88% and 79%, respectively. The sensitivity and specificity of a positive P wave in lead V1in predicting a left atrial focus was 93% and 88%, respectively.Conclusions.1) Analyses of surface P wave configuration proved to be reasonably good in differentiating right atrial from left atrial tachycardia foci. 2) Leads II, III and aVF were helpful in providing clues for differentiating superior from inferior foci

A trapped single ion inside a Bose-Einstein condensate

Improved control of the motional and internal quantum states of ultracold neutral atoms and ions has opened intriguing possibilities for quantum simulation and quantum computation. Many-body effects have been explored with hundreds of thousands of quantum-degenerate neutral atoms and coherent light-matter interfaces have been built. Systems of single or a few trapped ions have been used to demonstrate universal quantum computing algorithms and to detect variations of fundamental constants in precision atomic clocks. Until now, atomic quantum gases and single trapped ions have been treated separately in experiments. Here we investigate whether they can be advantageously combined into one hybrid system, by exploring the immersion of a single trapped ion into a Bose-Einstein condensate of neutral atoms. We demonstrate independent control over the two components within the hybrid system, study the fundamental interaction processes and observe sympathetic cooling of the single ion by the condensate. Our experiment calls for further research into the possibility of using this technique for the continuous cooling of quantum computers. We also anticipate that it will lead to explorations of entanglement in hybrid quantum systems and to fundamental studies of the decoherence of a single, locally controlled impurity particle coupled to a quantum environment

Loss of neuronal integrity during progressive HIV-1 infection of humanized mice.

Neuronal damage induced by ongoing human immunodeficiency virus type 1 (HIV-1) infection was investigated in humanized NOD/scid-IL-2Rγ(c)(null) mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4(+) T-cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and fluorescence emission, showed regional reduction of neuronal soma and synaptic architectures. This was evidenced by loss of microtubule-associated protein 2, synaptophysin, and neurofilament antigens. This study is the first, to our knowledge, demonstrating lost neuronal integrity after HIV-1 infection in humanized mice. As such, the model permits studies of the relationships between ongoing viral replication and virus-associated neurodegeneration

The Hydrogen Atom in Combined Electric and Magnetic Fields with Arbitrary Mutual Orientations

For the hydrogen atom in combined magnetic and electric fields we investigate the dependence of the quantum spectra, classical dynamics, and statistical distributions of energy levels on the mutual orientation of the two external fields. Resonance energies and oscillator strengths are obtained by exact diagonalization of the Hamiltonian in a complete basis set, even far above the ionization threshold. At high excitation energies around the Stark saddle point the eigenenergies exhibit strong level repulsions when the angle between the fields is varied. The large avoided crossings occur between states with the same approximately conserved principal quantum number, n, and this intramanifold mixing of states cannot be explained, not even qualitatively, by conventional perturbation theory. However, it is well reproduced by an extended perturbation theory which takes into account all couplings between the angular momentum and Runge-Lenz vector. The large avoided crossings are interpreted as a quantum manifestation of classical intramanifold chaos. This interpretation is supported by both classical Poincar\'e surfaces of section, which reveal a mixed regular-chaotic intramanifold dynamics, and the statistical analysis of nearest-neighbor-spacingComment: two-column version, 10 pages, REVTeX, 10 figures, uuencoded, submitted to Rhys. Rev.