Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial

BACKGROUND: Evidence for efficacy of disease-modifying drugs in multiple sclerosis (MS) comes from trials of short duration. We report results from a 16 y, retrospective follow-up of the pivotal interferon beta-1b (IFNB-1b) study. METHODS: The 372 trial patients were randomly assigned to placebo (n=123), IFNB-1b 50 microg (n=125) or IFNB-1b 250 microg (n=124) subcutaneously every other day for at least 2 y. Some remained randomised for up to 5 y but, subsequently, patients received treatment according to physicians' discretion. Patients were re-contacted and asked to participate. Efficacy related measures included MRI parameters, relapse rate, the Expanded Disability Status Scale, the Multiple Sclerosis Functional Composite Measure and conversion to secondary progressive MS. RESULTS: Of the 88.2% (328/372) of patients who were identified, 69.9% (260/372) had available case report forms. No differences in outcome between original randomisation groups could be discerned using standard disability and MRI measures. However, mortality rates among patients originally treated with IFNB-1b were lower than in the original placebo group (18.3% (20/109) for placebo versus 8.3% (9/108) for IFNB-1b 50 microg and 5.4% (6/111) for IFNB-1b 250 microg). CONCLUSIONS: The original treatment assignment could not be shown to influence standard assessments of long-term efficacy. On-study behaviour of patients was influenced by factors that could not be controlled with the sacrifice of randomisation and blinding. Mortality was higher in patients originally assigned to placebo than those who had received IFNB-1b 50 microg or 250 microg. The dataset provides important resources to explore early predictors of long-term outcome

Experimental plan for irradiation experiment HRB-21

Irradiation experiment HRB-21 is the first in a series of test capsules that are designed to provide a fuel-performance data base to be used for the validation of modular high-temperature gas-cooled reactor (MHTGR) coated-particle fuel performance models under MHTGR normal operating conditions and specific licensing basis events. Capsule HRB-21 will contain an advanced TRISO-P UCO/ThO{sub 2} - coated-particle fuel system with demonstrated low defective-particle fraction ({le}5 {times} 10{sup {minus}5}) and a heavy metal-contamination fraction ({le}1 {times} 10{sup {minus}5}) that meets MHTGR quality specifications. The coated particles and fuel compacts were fabricated in laboratory-scale facilities using MHTGR reference procedures at General Atomics (GA). Nearly 150,000 fissile and fertile particles will be irradiated in capsule HRB-21 at a mean volumetric fuel temperature of 975{degree}C and will achieve a peak fissile burnup of 26% fissions per initial metal atom (FIMA) while accumulating a fast neutron fluence of about 4.5 {times} 10{sup 25} neutrons/m{sup 2}. This experiment is a cooperative effort between the US Department of Energy (DOE) and the Japan Atomic Energy Research Institute (JAERI). The participants are the Oak Ridge National Laboratory (ORNL), GA, and the Tokai Research Establishment. Capsule HRB-21 will contain the US MHTGR fuel specimens, and a companion capsule, HRB-22, will contain the JAERI fuel. The irradiation will take place in the removable beryllium reflector facility of the High Flux Isotope Reactor (HFIR) at ORNL. The performance of the fuel during irradiation will be closely monitored through on-line fission gas release measurements. Detailed postirradiation examination and conduction cooldown simulation testing will be performed on the irradiated fuel compacts from both the HRB-21 and HRB-22 capsules. 5 refs., 9 figs., 6 tabs

The State of Manganese in the Photosynthetic Apparatus. Ii. X-Ray Absorption Edge Studies on Manganese in Photosynthetic Membranes

X-ray absorption spectra at the Manganese K-edge are presented for spinach chloroplasts, and chloroplasts which have been Tris-treated and hence unable to evolve oxygen. A significant change in the electronic environment of manganese is observed and is attributed to the release of manganese from the thylakoid membranes with a concomitant change in oxidation state. A correlation of the K-edge energy, defined as the energy at the first inflection point, with coordination charge has been established for a number of manganese compounds of known structure and oxidation state. Comparison of the manganese K-edge energies of the chloroplast samples with the reference compounds places the average oxidation state of the chloroplasts between +2 and +3. Using the edge spectra for Tris-treated membranes which were osmotically shocked to remove the released manganese, difference edge spectra were synthesized to approximate the active pool of manganese. Coordination charge predictions for this fraction are consistent with an average resting oxidation state higher than +2. The shape at the edge is also indicative of heterogeneity of the manganese site, of low symmetry, or both

Evidence of Hantavirus Infection among Bats in Brazil

Citation: Sabino-Santos, G., Maia, F. G. M., Vieira, T. M., Muylaert, R. D., Lima, S. M., Goncalves, C. B., . . . Figueiredo, L. T. M. (2015). Evidence of Hantavirus Infection among Bats in Brazil. American Journal of Tropical Medicine and Hygiene, 93(2), 404-406. doi:10.4269/ajtmh.15-0032Hantaviruses are zoonotic viruses harbored by rodents, bats, and shrews. At present, only rodent-borne hantaviruses are associated with severe illness in humans. New species of hantaviruses have been recently identified in bats and shrews greatly expanding the potential reservoirs and ranges of these viruses. Brazil has one of the highest incidences of hantavirus cardiopulmonary syndrome in South America, hence it is critical to know what is the prevalence of hantaviruses in Brazil. Although much is known about rodent reservoirs, little is known regarding bats. We captured 270 bats from February 2012 to April 2014. Serum was screened for the presence of antibodies against a recombinant nucleoprotein (rN) of Araraquara virus (ARAQV). The prevalence of antibody to hantavirus was 9/53 with an overall seroprevalence of 17%. Previous studies have shown only insectivorous bats to harbor hantavirus; however, in our study, of the nine seropositive bats, five were frugivorous, one was carnivorous, and three were sanguivorous phyllostomid bats

Problematizing Choice: Responsible consumers and sceptical citizens

About the book: Governance, Consumers and Citizens is the first book to bring together a study of governance with consumption, examining the changing place of the consumer as citizen in recent trends in governance, the tensions between competing ideas and practices of consumerism and the active role consumers play in the construction and practice of governance. Radically pushing forward the debate on consumers and governance, this collection outlines new conceptions and posits new policy agendas. Bringing together international experts from political science, history, geography, social policy and media studies, this study shows how governance and consumption are intertwined in crucial aspects of public policy and contemporary politics

"Actual" does not imply "feasible"

The familiar complaint that some ambitious proposal is infeasible naturally invites the following response: Once upon a time, the abolition of slavery and the enfranchisement of women seemed infeasible, yet these things were actually achieved. Presumably, then, many of those things that seem infeasible in our own time may well be achieved too and, thus, turn out to have been perfectly feasible after all. The Appeal to History, as we call it, is a bad argument. It is not true that if some desirable state of affairs was actually achieved, then it was feasible that it was achieved. “Actual” does not imply “feasible,” as we put it. Here is our objection. “Feasible” implies “not counterfactually fluky.” But “actual” does not imply “not counterfactually fluky.” So, “actual” does not imply “feasible.” While something like the Flukiness Objection is sometimes hinted at in the context of the related literature on abilities, it has not been developed in any detail, and both premises are inadequately motivated. We offer a novel articulation of the Flukiness Objection that is both more precise and better motivated. Our conclusions have important implications, not only for the admissible use of history in normative argument, but also by potentially circumscribing the normative claims that are applicable to us

Genotype-Phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures

Genetic susceptibility to multiple sclerosis (MS) is associated with the human leukocyte antigen (HLA) DRB1*1501 allele. Here we show a clear association between DRB1*1501 carrier status and four domains of disease severity in an investigation of genotype-phenotype associations in 505 robust, clinically well characterized MS patients evaluated cross-sectionally: (i) a reduction in the N-acetyl-aspartate (NAA) concentration within normal appearing white matter (NAWM) via 1HMR spectroscopy (P = 0.025), (ii) an increase in the volume of white matter (WM) lesions utilizing conventional anatomical MRI techniques (1,127 mm3; P = 0.031), (iii) a reduction in normalized brain parenchymal volume (nBPV) (P = 0.023), and (iv) impairments in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT-3) performance (Mean Z Score: DRB1*1501+: 0.110 versus DRB1*1501-: 0.048; P = 0.004). In addition, DRB1*1501+ patients had significantly more women (74% versus 63%; P = 0.009) and a younger mean age at disease onset (32.4 years versus 34.3 years; P = 0.025). Our findings suggest that DRB1*1501 increases disease severity in MS by facilitating the development of more T2-foci, thereby increasing the potential for irreversible axonal compromise and subsequent neuronal degeneration, as suggested by the reduction of NAA concentrations in NAWM, ultimately leading to a decline in brain volume. These structural aberrations may explain the significant differences in cognitive performance observed between DRB1*1501 groups. The overall goal of a deep phenotypic approach to MS is to develop an array of meaningful biomarkers to monitor the course of the disease, predict future disease behaviour, determine when treatment is necessary, and perhaps to more effectively recommend an available therapeutic interventio

Cosmopolitanism, Self-Interest and World Government

Cosmopolitans, if they are interested in seeing their principles realised, must hope that persons worldwide can become motivated to act in accordance with what those principles demand. But although it is important that genuinely moral motives are developed, we should not ignore the potential pragmatic value of self-interested motives to the realisation of cosmopolitan ends. This article considers three such motives: economic self-interest, prudent self-interest and democratic self-interest. I argue that in each case, usefully harnessing these motivations implies or requires global political integration that amounts to ‘world government’. This argument has the effect of reinforcing the already popular view that realising cosmopolitan principles entails global political integration. For those who already endorse that view, my argument will act as supporting evidence; by contrast it represents a challenge to those cosmopolitans who have remained ambivalent about, or indeed have explicitly rejected, the need for global political integration