Assessing the efficacy of cell transplantation for Parkinson's Disease: a patient-centered approach

Background: Evidence from a growing number of preclinical studies indicate that recently discovered stem cell lines may be translated into viable cellular therapies for people with Parkinson’s disease. Objectives: In a brief but critical review, we examine the use of primary and secondary outcome measures currently used to evaluate the efficacy of cellular therapies. Methods: The current practice of relying on a single primary outcome measure does not appear to provide the evidence required for demonstrating the robust, life-changing recovery anticipated with the successful implementation of cellular therapies. Results: We propose a 360-degree assessment protocol, which includes co-primary and composite outcome measures to provide accurate and comprehensive evidence of treatment efficacy, from the perspectives of both the researchers and the patients

Annular electroconvection with shear

We report experiments on convection driven by a radial electrical force in suspended annular smectic A liquid crystal films. In the absence of an externally imposed azimuthal shear, a stationary one-dimensional (1D) pattern consisting of symmetric vortex pairs is formed via a supercritical transition at the onset of convection. Shearing reduces the symmetries of the base state and produces a traveling 1D pattern whose basic periodic unit is a pair of asymmetric vortices. For a sufficiently large shear, the primary bifurcation changes from supercritical to subcritical. We describe measurements of the resulting hysteresis as a function of the shear at radius ratio $\eta \sim 0.8$. This simple pattern forming system has an unusual combination of symmetries and control parameters and should be amenable to quantitative theoretical analysis.Comment: 12 preprint pages, 3 figures in 2 parts each. For more info, see http://mobydick.physics.utoronto.c

Molecular flexibility of citrus pectins by combined sedimentation and viscosity analysis

The flexibility/rigidity of pectins plays an important part in their structure-function relationship and therefore on their commercial applications in the food and biomedical industries. Earlier studies based on sedimentation analysis in the ultracentrifuge have focused on molecular weight distributions and qualitative and semi-quantitative descriptions based on power law and Wales-van Holde treatments of conformation in terms of "extended" conformations [Harding, S. E., Berth, G., Ball, A., Mitchell, J.R., & Garcìa de la Torre, J. (1991). The molecular weight distribution and conformation of citrus pectins in solution studied by hydrodynamics. Carbohydrate Polymers, 168, 1-15; Morris, G. A., Foster, T. J., & Harding, S.E. (2000). The effect of degree of esterification on the hydrodynamic properties of citrus pectin. Food Hydrocolloids, 14, 227-235]. In the present study, four pectins of low degree of esterification 17-27% and one of high degree of esterification (70%) were characterised in aqueous solution (0.1 M NaCl) in terms of intrinsic viscosity [η], sedimentation coefficient (s°20,w) and weight average molar mass (Mw). Solution conformation/flexibility was estimated qualitatively using the conformation zoning method [Pavlov, G.M., Rowe, A.J., & Harding, S.E. (1997). Conformation zoning of large molecules using the analytical ultracentrifuge. Trends in Analytical Chemistry, 16, 401-405] and quantitatively (persistence length Lp) using the traditional Bohdanecky and Yamakawa-Fujii relations combined together by minimisation of a target function. Sedimentation conformation zoning showed an extended coil (Type C) conformation and persistence lengths all within the range Lp=10-13 nm (for a fixed mass per unit length)

Radial artery access site complications during cardiac procedures, clinical implications and potential solutions : the role of nitric oxide

Supported by the European Social Fund and Scottish Funding Council as part of Developing Scotland’s Workforce in the Scotland 2014-2020 European Structural and Investment Fund Programme.Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery, as this is safer than the femoral approach. However, despite improvements in technology and techniques, complications can occur. The most common complication, arterial spasm, can cause intense pain and, in some cases, procedural failure. The incidence of spasm is dependent on several variables, including operator experience, artery size, and equipment used. An anti-spasmolytic cocktail can be applied to reduce spasm, which usually includes an exogenous nitric oxide (NO) donor (glyceryl trinitrate). NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention. However, systemic administration can result in unwanted side-effects, such as hypotension. A method that adopts local delivery of NO might be advantageous. This review article describes the mechanisms involved in radial artery spasm, discusses the advantages and disadvantages of current strategies to reduce spasm, and highlight the potential of NO-loaded nanoporous materials for use in this setting.Publisher PDFPeer reviewe

Effect of Concurrent Partnerships and Sex-Act Rate on Gonorrhea Prevalence

The disease gonorrhea (GC) is a major public health problem in the United States, and the dynamics of the spread of GC through popula tions are complicated and not well understood. Studies have drawn attention to the effect of concurrent sexual partnerships as an influen tial factor for determining disease prevalence. However, little has been done to date to quantify the combined effects of concurrency and within-partnership sex-act rates on the prevalence of GC. This simulation study examines this issue with a simplified model of GC transmission in closed human populations that include concurrent partnerships. Two models of within-partnership sex-act rate are compared; one is a fixed sex-act rate per partnership, and the other is perhaps more realistic in that the rate depends on the number of concurrent partners. After controlling for total number of sex acts, pseudo-equilibrium prevalence is higher with the fixed sex-act rate than under the concurrency-adjusted rate in all the modeled partnership formation conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68414/2/10.1177_003754979807100404.pd

Hurricane Model Development at GFDL: A Collaborative Success Story From a Historical Perspective

The hurricane project at the National Oceanic and Atmospheric Administration (NOAA) Geophysical Fluid Dynamics Laboratory (GFDL) was established in 1970. By the mid-1970s pioneering research had led to the development of a new hurricane model. As the reputation of the model grew, GFDL was approached in 1986 by the director of the National Meteorological Center about establishing a collaboration between the two federal organizations to transition the model into an operational modeling system. After a multiyear effort by GFDL scientists to develop a system that could support rigorous requirements of operations, and multiyear testing had demonstrated its superior performance compared to existing guidance products, operational implementation was made in 1995. Through collaboration between GFDL and the U.S. Navy, the model was also made operational at Fleet Numerical Meteorology and Oceanography Center in 1996. GFDL scientists continued to support and improve the model during the next two decades by collaborating with other scientists at GFDL, the National Centers for Environmental Prediction (NCEP) Environmental Modeling Center (EMC), the National Hurricane Center, the U.S. Navy, the University of Rhode Island (URI), Old Dominion University, and the NOAA Hurricane Research Division. Scientists at GFDL, URI, and EMC collaborated to transfer key components of the GFDL model to the NWS new Hurricane Weather Research and Forecasting Model (HWRF) that became operational in 2007. The purpose of the article is to highlight the critical role of these collaborations. It is hoped that the experiences of the authors will serve as an example of how such collaboration can benefit the nation with improved weather guidance products

Spiral Defect Chaos in Large Aspect Ratio Rayleigh-Benard Convection

We report experiments on convection patterns in a cylindrical cell with a large aspect ratio. The fluid had a Prandtl number of approximately 1. We observed a chaotic pattern consisting of many rotating spirals and other defects in the parameter range where theory predicts that steady straight rolls should be stable. The correlation length of the pattern decreased rapidly with increasing control parameter so that the size of a correlated area became much smaller than the area of the cell. This suggests that the chaotic behavior is intrinsic to large aspect ratio geometries.Comment: Preprint of experimental paper submitted to Phys. Rev. Lett. May 12 1993. Text is preceeded by many TeX macros. Figures 1 and 2 are rather lon

Structural Properties, Order-Disorder Phenomena and Phase Stability of Orotic Acid Crystal Forms

Orotic acid (OTA) is reported to exist in the anhydrous (AH), monohydrate (Hy1) and dimethylsulfoxide monosolvate (SDMSO) forms. In this study we investigate the (de)hydration/desolvation behavior, aiming at an understanding of the elusive structural features of anhydrous OTA by a combination of experimental and computational techniques, namely, thermal analytical methods, gravimetric moisture (de)sorption studies, water activity measurements, X-ray powder diffraction, spectroscopy (vibrational, solid-state NMR), crystal energy landscape and chemical shift calculations. The Hy1 is a highly stable hydrate, which dissociates above 135°C and loses only a small part of the water when stored over desiccants (25°C) for more than one year. In Hy1, orotic acid and water molecules are linked by strong hydrogen bonds in nearly perfectly planar arranged stacked layers. The layers are spaced by 3.1 Å and not linked via hydrogen-bonds. Upon dehydration the X-ray powder diffraction and solid-state NMR peaks become broader indicating some disorder in the anhydrous form. The Hy1 stacking reflection (122) is maintained, suggesting that the OTA molecules are still arranged in stacked layers in the dehydration product. Desolvation of SDMSO, a non-layer structure, results in the same AH phase as observed upon dehydrating Hy1. Depending on the desolvation conditions different levels of order-disorder of layers present in anhydrous OTA are observed, which is also suggested by the computed low energy crystal structures. These structures provide models for stacking faults as intergrowth of different layers is possible. The variability in anhydrate crystals is of practical concern as it affects the moisture dependent stability of AH with respect to hydration