The inflammatory process of gout and its treatment.

Gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular deposits of monosodium urate (MSU) crystals. Important recent molecular biologic advances in this field have given us a clear picture of the mechanistic basis of gouty inflammation. The innate immune inflammatory response is critically involved in the pathology of gout. Specifically, MSU crystals promote inflammation directly by stimulating cells via Toll-like receptor signaling and by providing a surface for cleavage of C5 and formation of complement membrane attack complex (C5b-9), culminating in secretion of cytokines, chemokines, and other inflammatory mediators with a dramatic influx of neutrophils into the joint. Despite the detailed mechanistic picture for gouty inflammation, there are no placebo-controlled, randomized clinical studies for any of the therapies commonly used, although comparative studies have demonstrated that many nonsteroidal anti-inflammatory drugs are equivalent to indomethacin with respect to controlling acute gouty attacks. In general, the first line of anti-inflammatory therapy for acute gout is nonsteroidal anti-inflammatory drugs, and the selective cyclo-oxygenase-2 inhibitor celecoxib can be used where appropriate. The second line of treatment is glucocorticosteroids, given systemically (oral, intravenous, or intramuscular) or intra-articularly. Alternatively, synthetic adrenocorticotropic hormone is effective, partly via induction of adrenal glucocorticosteroids and partly via rapid peripheral suppression of leukocyte activation by melatonin receptor 3 signaling. The third line of treatment is oral colchicine, which is highly effective when given early in an acute gouty attack, but it is poorly tolerated because of predictable gastrointestinal side effects

The evolution of immune genes in tsetse flies (Glossina) and insights into tsetse-symbiont-trypanosome interactions

Tsetse flies (genera Glossina) are the sole biological vectors of African Trypanosoma species, the infectious agents of African Trypanosomiasis. Vector control is a key inhibitor of disease transmission; however, long-term control measures are economically and ecologically unsustainable and therefore, alternatives must be explored. In this thesis we aim to explore the evolution of three important immune genes: attacin-A (AttA), Defensin (Def) and Toll-like receptor 2 (TLR2), in relation to symbionts and parasitic interactions. This could in turn lay the foundations for genetic control methods The successful identification of novel attacin orthologues confirmed the previous descriptions of attacin clusters within the Glossina genome, while a single novel defensin orthologue was identified in each of the six Glossina genomes. A total of six TLRs were confirmed within the Glossina genome, and three additional TLRs were potentially identified, though these are unconfirmed. The evolutionary history of the attacin cluster remains undetermined, however concerted evolution likely impacts the evolution of AttA, while Def and TLRs are governed by strict Darwinian selection. A wild population sample of Glossina morsitans morsitans illustrated differing levels of nucleotide variation in each gene, Def being the least polymorphic (n = 8) and TLR2 being the most (n = 22). All genes indicated a recent population expansion event and deviations from neutrality, indicative of population expansion and balancing selection. Genetic variation in both AttA and TLR2 was found to be maintained via purifying selection, while Def exhibited signs of the Red Queen arms race and balancing section. Trypanosome infection rates were unexpectedly high (69.35%), consisting of mixed species infections. Advantageous Def variants were observed to reduce infection rates within samples, while an observable relationship between TLR2 and symbiont variation, and infection rate requires further research. The results within described the impacts of evolution and population change on immune genes and how the interactions with symbiont populations can influence trypanosome infection rates. This thesis indicates that an understanding of the evolution and interactions of the tsetse-symbiont-trypanosome triplet could be used to inform novel genetic control methods

RISK AND RETURN IN AGRICULTURE: EVIDENCE FROM AN EXPLICIT-FACTOR ARBITRAGE PRICING MODEL

This article develops and estimates an explicit-factor Arbitrage Pricing Theory (APT) model in an endeavor to uncover (a) the systematic risk properties of returns to agricultural assets, (b) the relationship between agricultural returns and returns on comparable-risk nonagricultural assets, and (c) the possible relevance of agriculture-related risks in general capital markets. The article concludes that: (a) farmer-held assets have exhibited significant systematic/ factor risk over the 1963-82 estimation interval, but U.S. farmland has not exhibited such risk; (b) a grain-price index has been a priced factor in general capital markets; and (c) average returns on farmer-held assets have been significantly lower; and average returns on U.S. farmland significantly higher, than those on comparable-risk nonagricultural assets.Agricultural Finance,

Canada's Nuclear Crossroads: Steps to a Viable Nuclear Energy Industry

Canada is at an energy and environmental crossroad. Fossil fuels cause environmental damage and the growth potential of large-scale hydroelectricity is limited. Policymakers are reconsidering the merits of nuclear power as both a low-carbon emitting and low-cost base load electricity source. While nuclear power may look like an attractive option, nuclear power must overcome problems such as the high and uncertain cost of construction, dealing with nuclear waste, reactor licensing and regulation, and the future of Canada’s nuclear reactor builder, Atomic Energy of Canada Limited (AECL), a federal Crown corporation.economic growth and innovation, energy and environmental policy

Ten Micron Photometry of 25 Stars from B8 To M7

A photometer employing a liquid hydrogen-cooled mercury-doped germanium photoconductor whose spectral response is limited to the 8 - 14 µ region by a low pass interference filter and a BaF_2 window coupled with the cell's threshold wavelength has been placed at the east arm Cassegrain focus of the 200 inch Hale telescope. Twenty-five stars have been measured. The earliest star for which two measurements have been obtained is the B8Ia star β Orionis. The latest star is the M7e star X Cygni. The brightest star, L37 X 10^(-14) watts/cm^2, is α Orionis. The carbon star DS Peg was also measured. In a two-color diagram formed with B and V there is an intrinsic increase in dispersion going to later type stars and a systematic trend away from the blackbody relation. The ratios of the stellar fluxes to those expected from blackbodies at the published stellar effective-temperatures and angular diameters are not far from one. A systematic trend exhibited may not be real because of the assumptions involved in inteferometric diameter determinations. DS Peg does not appear overly peculiar in the two-color plots, but X,Cygni falls on the opposite side of the blackbody curve ("blue excess") compared with most of the late type stars. The fluxes presented here have not been corrected for presently uncertain telescope transmission losses which may be important

Selective Screening of Rail Passengers, MTI 06-07

The threat of another major terrorist attack in the United States remains high, with the greatest danger coming from local extremists inspired by events in the Middle East. Although the United States removed the Taliban government and destroyed al Qaeda’s training camps in Afghanistan, events in Europe and elsewhere have shown that the terrorist network leadership remains determined to carry out further attacks and is capable of doing so. Therefore, the United States must systematically conduct research on terrorist strikes against transportation targets to distill lessons learned and determine the best practices for deterrence, response, and recovery. Those best practices must be taught to transportation and security professionals to provide secure surface transportation for the nation. Studying recent incidents in Europe and Asia, along with other research, will help leaders in the United States learn valuable lessons—from preventing attacks, to response and recovery, to addressing the psychological impacts of attacks to business continuity. Timely distillations of the lessons learned and best practices developed in other countries, once distributed to law enforcement, first responders, and rail- and subway-operating transit agencies, could result in the saving of American lives. This monograph focuses on the terrorist risks confronting public transportation in the United States—especially urban mass transit—and explores how different forms of passenger screening, and in particular, selective screening, can best be implemented to reduce those risks