Are the average gait speeds during the 10 meter and 6 minute walk tests redundant in Parkinson disease?

Published in final edited form as: Gait Posture. 2017 February ; 52: 178–182. doi:10.1016/j.gaitpost.2016.11.033.We investigated the relationships between average gait speed collected with the 10Meter Walk Test (Comfortable and Fast) and 6Minute Walk Test (6MWT) in 346 people with Parkinson disease (PD) and how the relationships change with increasing disease severity. Pearson correlation and linear regression analyses determined relationships between 10Meter Walk Test and 6MWT gait speed values for the entire sample and for sub-samples stratified by Hoehn & Yahr (H&Y) stage I (n=53), II (n=141), III (n=135) and IV (n=17). We hypothesized that redundant tests would be highly and significantly correlated (i.e. r>0.70, p<0.05) and would have a linear regression model slope of 1 and intercept of 0. For the entire sample, 6MWT gait speed was significantly (p<0.001) related to the Comfortable 10 Meter Walk Test (r=0.75) and Fast 10Meter Walk Test (r=0.79) gait speed, with 56% and 62% of the variance in 6MWT gait speed explained, respectively. The regression model of 6MWT gait speed predicted by Comfortable 10 Meter Walk gait speed produced slope and intercept values near 1 and 0, respectively, especially for participants in H&Y stages II-IV. In contrast, slope and intercept values were further from 1 and 0, respectively, for the Fast 10Meter Walk Test. Comfortable 10 Meter Walk Test and 6MWT gait speeds appeared to be redundant in people with moderate to severe PD, suggesting the Comfortable 10 Meter Walk Test can be used to estimate 6MWT distance in this population.This study was funded by the Davis Phinney Foundation, the Parkinson's Disease Foundation, and the National Institutes of Health (R01 NS077959, K12 HD055931, UL1 TR000448). The funding sources had no input related to study design, data collection, or decision to submit for publication. (Davis Phinney Foundation; Parkinson's Disease Foundation; R01 NS077959 - National Institutes of Health; K12 HD055931 - National Institutes of Health; UL1 TR000448 - National Institutes of Health

Configuration development study of the X-24C hypersonic research airplane

Bottom line results were made of a three-phase study to determine the feasibility of designing, building, and operating, and maintaining an air-launched high performance aircraft capable of cruising at speeds up to Mach 8 for short durations. The results show that Lockalloy heat-sink structure affords the capability for a 'work-horse' vehicle which can serve as an excellent platform for this research. It was further concluded that the performance of a blended wing body configuration surpassed that of a lifting body design for typical X-24C missions. The cost of a two vehicle program, less engines, B-52 modification and contractor support after delivery, can be kept within $70M (in Jan. 1976 dollars)

Geochronology of late Pleistocene to Holocene speleothems from central Texas: Implications for regional paleoclimate

from a southward deflection of the jet steam due to the presence of a continental ice sheet in central North America. This mechanism also may have governed the two earlier intervals of fast growth in the speleothems (and inferred wetter climate). Ice volumes were lower and temperatures in central North America were higher during these two earlier glacial intervals than during the Last Glacial Maximum, however. The potential effects of temporal variations in precession of Earth&apos;s orbit on regional effective moisture may provide an additional mechanism for increased effective moisture coincident with the observed intervals of increased speleothem growth. The stalagmites all exhibit a large drop in growth rate between 15 and 12 ka, and they show very slow growth up to the present, consistent with drier climate during the Holocene. These results illustrate that speleothem growth rates can reflect the regional response of a hydrologic system to regional and global climate variability

APP Regulates Microglial Phenotype in a Mouse Model of Alzheimer\u27s Disease

Prior work suggests that amyloid precursor protein (APP) can function as a proinflammatory receptor on immune cells, such as monocytes and microglia. Therefore, we hypothesized that APP serves this function in microglia during Alzheimer\u27s disease. Although fibrillar amyloid β (Aβ)-stimulated cytokine secretion from both wild-type and APP knock-out (mAPP−/−) microglial cultures, oligomeric Aβ was unable to stimulate increased secretion from mAPP−/− cells. This was consistent with an ability of oligomeric Aβ to bind APP. Similarly, intracerebroventricular infusions of oligomeric Aβ produced less microgliosis in mAPP−/− mice compared with wild-type mice. The mAPP−/− mice crossed to an APP/PS1 transgenic mouse line demonstrated reduced microgliosis and cytokine levels and improved memory compared with wild-type mice despite robust fibrillar Aβ plaque deposition. These data define a novel function for microglial APP in regulating their ability to acquire a proinflammatory phenotype during disease. SIGNIFICANCE STATEMENT A hallmark of Alzheimer\u27s disease (AD) brains is the accumulation of amyloid β (Aβ) peptide within plaques robustly invested with reactive microglia. This supports the notion that Aβ stimulation of microglial activation is one source of brain inflammatory changes during disease. Aβ is a cleavage product of the ubiquitously expressed amyloid precursor protein (APP) and is able to self-associate into a wide variety of differently sized and structurally distinct multimers. In this study, we demonstrate both in vitro and in vivo that nonfibrillar, oligomeric forms of Aβ are able to interact with the parent APP protein to stimulate microglial activation. This provides a mechanism by which metabolism of APP results in possible autocrine or paracrine Aβ production to drive the microgliosis associated with AD brains

Organizational Configurations and Performance: A Meta-Analysis

The link between organizational configurations and performance has become a central and somewhat controversial focus of research in the strategic management literature, We statistically aggregated results from 40 original tests of the configurations-performance relationship. In contrast to previous qualitative reviews, this meta-analysis demonstrated that an organization\u27s performance is partially explained by its configuration. Tests of four potential moderators showed that organizations\u27 configurations contributed more to performance explanation to the extent that studies used (1) broad definitions of configurations, (2) single-industry samples, and (3) longitudinal designs, Results highlight the need for programmatic research

Global population divergence and admixture of the brown rat (Rattus norvegicus)

Native to China and Mongolia, the brown rat (Rattus norvegicus) now enjoys a worldwide distribution. While black rats and the house mouse tracked the regional development of human agricultural settlements, brown rats did not appear in Europe until the 1500s, suggesting their range expansion was a response to relatively recent increases in global trade. We inferred the global phylogeography of brown rats using 32 k SNPs, and detected 13 evolutionary clusters within five expansion routes. One cluster arose following a southward expansion into Southeast Asia. Three additional clusters arose from two independent eastward expansions: one expansion from Russia to the Aleutian Archipelago, and a second to western North America. Westward expansion resulted in the colonization of Europe from which subsequent rapid colonization of Africa, the Americas and Australasia occurred, and multiple evolutionary clusters were detected. An astonishing degree of fine-grained clustering between and within sampling sites underscored the extent to which urban heterogeneity shaped genetic structure of commensal rodents. Surprisingly, few individuals were recent migrants, suggesting that recruitment into established populations is limited. Understanding the global population structure of R. norvegicus offers novel perspectives on the forces driving the spread of zoonotic disease, and aids in development of rat eradication programmes

The determinants of election to the United Nations Security Council

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11127-013-0096-4.The United Nations Security Council (UNSC) is the foremost international body responsible for the maintenance of international peace and security. Members vote on issues of global importance and consequently receive perks—election to the UNSC predicts, for instance, World Bank and IMF loans. But who gets elected to the UNSC? Addressing this question empirically is not straightforward as it requires a model that allows for discrete choices at the regional and international levels; the former nominates candidates while the latter ratifies them. Using an original multiple discrete choice model to analyze a dataset of 180 elections from 1970 to 2005, we find that UNSC election appears to derive from a compromise between the demands of populous countries to win election more frequently and a norm of giving each country its turn. We also find evidence that richer countries from the developing world win election more often, while involvement in warfare lowers election probability. By contrast, development aid does not predict election

The Treasured Hunt: Collecting Medieval and Renaissance Manuscripts, Past, Present, and Future

Welcome and Opening Remarks: E. Ann Matter, University of Pennsylvania, and Lynn Ransom, Free Library of Philadelphia Session 1. Beginnings: Collecting in the Middle Ages and Renaissance Session Chair: Emily Steiner, Department of English, University of Pennsylvania Claire Richter Sherman, Center for Advanced Study in the Visual Arts at the National Gallery of Art, The Manuscript Collection of King Charles V of France: The Personal and the Political David Rundle, History Faculty and Corpus Christi College, Oxford University, The Butcher of England and the Renaissance Arts of Book-Collecting Session 2: Civic Service: The Legacies of Philadelphia-Area Collectors Chair: Peter Stallybrass, Department of English, University of Pennsylvania James Tanis, Director of Libraries and Professor of History Emeritus, Bryn Mawr College, Migrating Manuscripts Derick Dreher, Director, The Rosenbach Museum & Library, Of Private Collectors and Public Libraries: Dr. A. S. W. Rosenbach and John Frederick Lewis Session 3: Keynote address Welcome: H. Carton Rogers, Vice Provost & Director of Libraries, University of Pennsylvania Chair: Robert Maxwell, Department of the History of Art, University of Pennsylvania Christopher de Hamel, Gaylord Donnelley Fellow Librarian, Corpus Christi College, Cambridge University, The Manuscript Collection of C. L. Ricketts (1859-1941) Session 4: The Hunters and the Hunted: A Roundtable Discussion with Private and Institutional Collectors Chair: David Wallace, Department of English, University of Pennsylvania Moderator: Richard Linenthal, Bernard Quaritch Ltd. Panelists: Lawrence J. Schoenberg, Private Collector Gifford Combs, Private Collector Toshiyuki Takamiya, Private Collector, Keio University Consuelo Dutschke, Curator of Medieval and Renaissance Manuscripts, Columbia University William Noel, Curator of Manuscripts and Rare Books, The Walters Art Museu

LPS INHIBITION OF GLUCOSE PRODUCTION THROUGH THE TLR4, MYD88, NFκB PATHWAY

Acute exposure to lipopolysaccharide (LPS) can cause hypoglycemia and insulin resistance; the underlying mechanisms however, are unclear. We set out to determine whether insulin resistance is linked to hypoglycemia through TLR4, MyD88 and NFκB, a cell signaling pathway that mediates LPS induction of the proinflammatory cytokine TNFα. LPS induction of hypoglycemia was blocked in TLR4−/− and MyD88−/− mice but not in TNFα−/− mice. Both glucose production and glucose utilization were decreased during hypoglycemia. Hypoglycemia was associated with the activation of NFκB in the liver. LPS inhibition of glucose production was blocked in hepatocytes isolated from TLR4−/− and MyD88−/− mice and hepatoma cells expressing an IκB mutant that interferes with NFκB activation. Thus, LPS-induced hypoglycemia was mediated by the inhibition of glucose production from the liver through the TLR4, MyD88, NFκB pathway, independent of LPS induced TNFα. LPS inhibition of glucose production was not blocked by pharmacologic inhibition of the insulin signaling intermediate PI3K in hepatoma cells. Insulin injection caused a similar reduction of circulating glucose in TLR4−/− and TLR4+/+ mice. These two results suggest that LPS and insulin inhibit glucose production by separate pathways. Recovery from LPS induced hypoglycemia was linked to glucose intolerance and hyperinsulinemia in TLR4+/+ mice, but not in TLR4−/− mice

Pulse Jet Mixer Overblow Testing for Assessment of Loadings During Multiple Overblows

The U.S. Department of Energy (DOE) Office of River Protection’s Waste Treatment Plant (WTP) is being designed and built to pretreat and then vitrify a large portion of the wastes in Hanford’s 177 underground waste storage tanks. The WTP consists of three primary facilities: pretreatment, low-activity waste (LAW) vitrification, and high-level waste (HLW) vitrification. The pretreatment facility will receive waste feed from the Hanford tank farms and separate it into 1) a high-volume, low-activity liquid stream stripped of most solids and radionuclides and 2) a much smaller volume of HLW slurry containing most of the solids and most of the radioactivity. Many of the vessels in the pretreatment facility will contain pulse jet mixers (PJMs) that will provide some or all of the mixing in the vessels. This technology was selected for use in so-called “black cell” regions of the WTP, where maintenance capability will not be available for the operating life of the WTP. PJM technology was selected for use in these regions because it has no moving mechanical parts that require maintenance. The vessels with the most concentrated slurries will also be mixed with air spargers and/or steady jets in addition to the mixing provided by the PJMs. This report contains the results of single and multiple PJM overblow tests conducted in a large, ~13 ft-diameter × 15-ft-tall tank located in the high bay of the Pacific Northwest National Laboratory (PNNL) 336 Building test facility. These single and multiple PJM overblow tests were conducted using water and a clay simulant to bound the lower and upper rheological properties of the waste streams anticipated to be processed in the WTP. Hydrodynamic pressures were measured at a number of locations in the test vessel using an array of nine pressure sensors and four hydrophones. These measurements were made under normal and limiting vessel operating conditions (i.e., maximum PJM fluid emptying velocity, maximum and minimum vessel contents for PJM operation, and maximum and minimum rheological properties). Test data collected from the PJM overblow tests were provided to Bechtel National, Inc. (BNI) for assessing hydrostatic, dynamic, and acoustic pressure loadings on in-tank structures during 1) single overblows; 2) multiple overlapping overblows of two to four PJMs; 3) simultaneous overblows of pairs of PJMs