Developing Retina and PNS Segments for Transplantation Into the Adult Host Eye: Reconstruction of the Mammalian Visual System. 1. Methodology

Various techniques have been explored to determine the uses and limitations of techniques that enable the adult CNS to regenerate, but relatively little attention has been given to the consideration of a "reconstructed" visual system. Using this approach, one can design experiments to study the uses of exogenous tissues in reestablishing neuronal circuits that have been damaged. Toward this end, experiments were designed to determine whether embryonic retinal ganglion cells can project axons into a grafted PNS "bridge", and enter adult host targets that were partially deafferented. Embryonic eyes of E11, E14, E18 and E21 rats were sutured to peripheral nerve segments which served as bridges between the host eye and frontal cortex. Projections between the developing retina and the host brain could then be evaluated using HRP tracing techniques. From a methodological standpoint, the preparations are 65% effective; i.e., a viable bridge results between the embryonic eye and the host forebrain. The results presented in the accompanying paper demonstrate that the technique can yield results indicative of embryonic retinal development and axonal projection through the graft and into the host brain. This partial reconstruction of the visual system may prove a useful tool in understanding the uses and limitations of grafting in the CNS

Hubble Space Telescope Astrometry of the Procyon System

The nearby star Procyon is a visual binary containing the F5 IV-V subgiant Procyon A, orbited in a 40.84 yr period by the faint DQZ white dwarf Procyon B. Using images obtained over two decades with the Hubble Space Telescope, and historical measurements back to the 19th century, we have determined precise orbital elements. Combined with measurements of the parallax and the motion of the A component, these elements yield dynamical masses of 1.478 +/- 0.012 Msun and 0.592 +/- 0.006 Msun for A and B, respectively. The mass of Procyon A agrees well with theoretical predictions based on asteroseismology and its temperature and luminosity. Use of a standard core-overshoot model agrees best for a surprisingly high amount of core overshoot. Under these modeling assumptions, Procyon A's age is ~2.7 Gyr. Procyon B's location in the H-R diagram is in excellent agreement with theoretical cooling tracks for white dwarfs of its dynamical mass. Its position in the mass-radius plane is also consistent with theory, assuming a carbon-oxygen core and a helium-dominated atmosphere. Its progenitor's mass was 1.9-2.2 Msun, depending on its amount of core overshoot. Several astrophysical puzzles remain. In the progenitor system, the stars at periastron were separated by only ~5 AU, which might have led to tidal interactions and even mass transfer; yet there is no direct evidence that these have occurred. Moreover the orbital eccentricity has remained high (~0.40). The mass of Procyon B is somewhat lower than anticipated from the initial-to-final-mass relation seen in open clusters. The presence of heavy elements in its atmosphere requires ongoing accretion, but the place of origin is uncertain.Comment: Accepted by Astrophysical Journa

Development of a minimization instrument for allocation of a hospital-level performance improvement intervention to reduce waiting times in Ontario emergency departments

<p>Abstract</p> <p>Background</p> <p>Rigorous evaluation of an intervention requires that its allocation be unbiased with respect to confounders; this is especially difficult in complex, system-wide healthcare interventions. We developed a short survey instrument to identify factors for a minimization algorithm for the allocation of a hospital-level intervention to reduce emergency department (ED) waiting times in Ontario, Canada.</p> <p>Methods</p> <p>Potential confounders influencing the intervention's success were identified by literature review, and grouped by healthcare setting specific change stages. An international multi-disciplinary (clinical, administrative, decision maker, management) panel evaluated these factors in a two-stage modified-delphi and nominal group process based on four domains: change readiness, evidence base, face validity, and clarity of definition.</p> <p>Results</p> <p>An original set of 33 factors were identified from the literature. The panel reduced the list to 12 in the first round survey. In the second survey, experts scored each factor according to the four domains; summary scores and consensus discussion resulted in the final selection and measurement of four hospital-level factors to be used in the minimization algorithm: improved patient flow as a hospital's leadership priority; physicians' receptiveness to organizational change; efficiency of bed management; and physician incentives supporting the change goal.</p> <p>Conclusion</p> <p>We developed a simple tool designed to gather data from senior hospital administrators on factors likely to affect the success of a hospital patient flow improvement intervention. A minimization algorithm will ensure balanced allocation of the intervention with respect to these factors in study hospitals.</p

Capillary Density of Skeletal Muscle: A Contributing Mechanism for Exercise Intolerance in Class II–III Chronic Heart Failure Independent of Other Peripheral Alterations

AbstractOBJECTIVESThe study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II–III chronic heart failure (CHF).BACKGROUNDPrevious studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF.METHODSThe present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients. Aerobic capacities, myosin heavy chain (MHC) isoforms, enzymes, and capillary density were measured.RESULTSThe patients with CHF demonstrated a reduced peak oxygen consumption when compared to controls (15.0 ± 2.5 vs. 19.8 ± 5.0 ml·kg−1·min−1, p <0.05). Using cell-specific antibodies to directly assess vascular density, there was a reduction in capillary density in CHF measured as the number of endothelial cells/fiber (1.42 ± 0.28 vs. 1.74 ± 0.35, p = 0.02). In CHF, capillary density was inversely related to maximal oxygen consumption (r = 0.479, p = 0.02). The MHC IIx isoform was found to be higher in patients with CHF versus normal subjects (28.5 ± 13.6 vs. 19.5 ± 9.4, p <0.05).CONCLUSIONSThere was a significant reduction in microvascular density in patients with CHF compared with the control group, without major differences in other usual histologic and biochemical aerobic markers. The inverse relationship with peak oxygen consumption seen in the CHF group suggests that a reduction in microvascular density of skeletal muscle may precede other skeletal muscle alterations and play a critical role in the exercise intolerance characteristic of patients with CHF