Exogenous schwann cells migrate, remyelinate and promote clinical recovery in experimental auto-immune encephalomyelitis

Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs) allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed Pzero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease

Chronostratigraphy and geochronology: a proposed realignment

We propose a realignment of the terms geochronology and chronostratigraphy that brings them broadly into line with current use, while simultaneously resolving the debate over whether the Geological Time Scale should have a “single” or “dual” hierarchy of units: Both parallel sets of units are retained, although there remains the option to adopt either a single (i.e., geochronological) or a dual hierarchy in particular studies, as considered appropri-ate. Thus, geochronology expresses the timing or age of events (depositional, diagenetic, biotic, climatic, tectonic, magmatic) in Earth’s history (e.g., Hirnantian glaciation, Famennian-Frasnian mass extinction). Geochronology can also qualify rock bodies, stratified or unstratified, with respect to the time interval(s) in which they formed (e.g., Early Ordovician Ibex Group). In addition, geochronology refers to all methods of numerical dating. Chronostratigraphy would include all methods (e.g., biostrati-graphy, magnetostratigraphy, chemostratigraphy, cyclostrati-graphy, sequence stratigraphy) for (1) establishing the relative time relationships of stratigraphic successions regionally and worldwide; and (2) formally naming bodies of stratified rock that were deposited contemporaneously with units formally defined at their base, ideally by a GSSP (Global Boundary Stratotype Section and Point = “golden spike”) that represents a specific point in time. Geochronologic units may be defined and applied generally by either GSSPs or—as currently in most of the Precambrian—by Global Standard Stratigraphic Ages (GSSAs). Geochronologic units would continue as the time units eons/eras/periods/epochs/ages, and chronostratigraphic units as the time-rock units eonothems/erathems/systems/series/stages. Both hierarchies would remain available for use, as recommended by a formal vote of the International Commission on Stratigraphy in 2010. Geological context helps determine the appropriate usage of the component units

Managed Care for Elderly People: A Compendium of Findings

Although managed care seems to serve well the in terests of non-elderly enrollees and their payers, elderly people face more risks. Chronic conditions, multiple prob lems, and more limited resources make them more vul nerable, whereas multiple payer sources make them more complicated to cover. This synthesis of managed care de livered in Medicare and Medicaid demonstration projects serving elderly beneficiaries shows that managed care plans either select or attract enrollees who suffer fewer frailties than those served in fee-for-service settings, ex hibit reluctance to enter rural markets, provide a broad range of elderly-specific services, offer more compre hensive coverage and services, and result in greater per ceived access problems, particularly for vulnerable subgroups. Plans operate more cheaply by using fewer resources, even after adjusting for case mix differences. Managed care enrollees tend to be more satisfied with financial and coverage aspects, whereas fee-for-service enrollees report higher satisfaction on other dimensions. In acute care settings, process of care findings were mixed, whereas clinical and self-reported outcome indi cators were no better and in some instances worse in managed care. Long-term care enrollees, in the few stud ies reported, consistently faired worse in both the processes and outcomes of care. These findings suggest that further research on the effects of managed care in its rapidly changing incarnations is needed, particularly with respect to how to improve the quality of acute and long-term care delivered to elderly people and the proper role of government and other key actors in the health care system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66514/2/10.1177_106286069801300304.pd

Seawater redox variations during the deposition of the Kimmeridge Clay Formation, United Kingdom (Upper Jurassic): evidence from molybdenum isotopes and trace metal ratios

The Kimmeridge Clay Formation (KCF) and its equivalents worldwide represent one of the most prolonged periods of organic carbon accumulation of the Mesozoic. In this study, we use the molybdenum (Mo) stable isotope system in conjunction with a range of trace metal paleoredox proxies to assess how seawater redox varied both locally and globally during the deposition of the KCF. Facies with lower organic carbon contents (TOC 1–7 wt %) were deposited under mildly reducing (suboxic) conditions, while organic-rich facies (TOC >7 wt %) accumulated under more strongly reducing (anoxic or euxinic) local conditions. Trace metal abundances are closely linked to TOC content, suggesting that the intensity of reducing conditions varied repeatedly during the deposition of the KCF and may have been related to orbitally controlled climate changes. Long-term variations in ?98/95Mo are associated with the formation of organic-rich intervals and are related to third-order fluctuations in relative sea level. Differences in the mean ?98/95Mo composition of the organic-rich intervals suggest that the global distribution of reducing conditions was more extensive during the deposition of the Pectinatites wheatleyensis and lower Pectinatites hudlestoni zones than during the deposition of the upper Pectinatites hudlestoni and Pectinatites pectinatus zones. The global extent of reducing conditions during the Kimmerigidan was greater than today but was less widespread than during the Toarcian (Early Jurassic) oceanic anoxic event. This study also demonstrates that the Mo isotope system in Jurassic seawater responded to changes in redox conditions in a manner consistent with its behavior in present-day sedimentary environment

Subnational climate entrepreneurship: innovative climate action in California and São Paulo

The distinct role of subnational governments such as states and provinces in addressing climate change has been increasingly acknowledged. But while most studies investigate the causes and consequences of particular governments’ actions and networking activities, this article argues that subnational governments can develop climate action as a collective entrepreneurial activity. Addressing many elements explored in this special issue, it focuses on the second question and identifies climate entrepreneurship in two subnational governments—the states of California (USA) and São Paulo (Brazil). Examining internal action, as well as interaction with local authorities, national governments and the international regime, entrepreneurial activities are identified in the invention, diffusion and evaluation of subnational climate policy in each case. The article draws from the recent scholarship on policy innovation, entrepreneurship and climate governance. It contributes to the literature by exploring entrepreneurial subnational government activity in addressing climate change and expanding the understanding of the effects of policy innovation at the subnational level

BurkDiff: A Real-Time PCR Allelic Discrimination Assay for Burkholderia Pseudomallei and B. mallei

A real-time PCR assay, BurkDiff, was designed to target a unique conserved region in the B. pseudomallei and B. mallei genomes containing a SNP that differentiates the two species. Sensitivity and specificity were assessed by screening BurkDiff across 469 isolates of B. pseudomallei, 49 isolates of B. mallei, and 390 isolates of clinically relevant non-target species. Concordance of results with traditional speciation methods and no cross-reactivity to non-target species show BurkDiff is a robust, highly validated assay for the detection and differentiation of B. pseudomallei and B. mallei

An extraterrestrial trigger for the Early Cretaceous massive volcanism? Evidence from the paleo-Tethys Ocean

The Early Cretaceous Greater Ontong Java Event in the Pacific Ocean may have covered ca. 1% of the Earth's surface with volcanism. It has puzzled scientists trying to explain its origin by several mechanisms possible on Earth, leading others to propose an extraterrestrial trigger to explain this event. A large oceanic extraterrestrial impact causing such voluminous volcanism may have traces of its distal ejecta in sedimentary rocks around the basin, including the paleo-Tethys Ocean which was then contiguous with the Pacific Ocean. The contemporaneous marine sequence at central Italy, containing the sedimentary expression of a global oceanic anoxic event (OAE1a), may have recorded such ocurrence as indicated by two stratigraphic intervals with 187Os/188Os indicative of meteoritic influence. Here we show, for the first time, that platinum group element abundances and inter-element ratios in this paleo-Tethyan marine sequence provide no evidence for an extraterrestrial trigger for the Early Cretaceous massive volcanism