362 research outputs found

    A Competitive Bidding Approach to Medicare Reform

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    Medicare reform is a critical issue for the public agenda. The most promising option for addressing Medicare reform is competitive bidding -- using health plans' bids to determine the government's contribution to a basic set of benefits in every market area. This paper begins with a review of the history of competitive bidding in Medicare. It then moves to a definition of terms, which is crucial in any discussion of competitive pricing because the often-heated public debate around these issues frequently distorts positions and confuses issues by conflating different terms and making some arguments appear other than they are. Following this terminological exercise, the report includes a series of sections discussing competitive bidding in Medicare, with special focus on the challenges to introducing it

    Linear optical properties of Ge nanocrystals in silica

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    The absorption and extinctionspectra of Genanocrystals in silica formed by ion implantation are studied using photothermal deflection and transmission spectroscopies. It is found that scattering makes a significant contribution to the extinction spectrum, damping the spectral features and resulting in a Rayleigh scattering-likeω⁴ dependence. In contrast, the spectra measured by photothermal deflection clearly show features such as the E1/E1+Δ1 transitions. The Tauc gap is extracted to be ∼0.7±0.1 eV

    Setting Physicians\u27 Prices in FFS Medicare: An Economic Perspective

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    Recent policy discussions by the Medicare Payment Advisory Commission (MedPAC) regarding physician prices in the traditional fee-for-service (FFS) Medicare Program reflect movement toward a market pricing model. Earlier objectives such as sustainable levels of spending have given way to concerns over the relationship between fees and actual costs, access to care, and the importance of demand and supply in local markets. An important objective in other policy settings is economically efficient distribution of services. We explain the meaning of economic efficiency for Medicare physician prices and explore difficulties one might encounter in pursuing economic efficiency, as well as the cost of not pursuing it

    Recent Cases

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    Insect resistance of a full sib family of tetraploid switchgrass \u3ci\u3ePanicum virgatum\u3c/i\u3e L. with varying lignin levels

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    Little information is available on insect resistance mechanisms and inheritance in biomass grasses. Although reduction of lignin in biomass grasses in order to increase the efficiency of fermentation may result in increased susceptibility to insect feeding, other resistance mechanisms may be more important. Field grown leaves of two tetraploid parent (Kanlow N1, Summer) and 14 progeny switchgrass (Panicum virgatum L.) plant clones selected for a diversity of plant form and ranges in lignin levels were tested for leaf resistance to feeding by the fall armyworm (Spodoptera frugiperda J. E. Smith), a grass feeding insect pest. Although lignin generally appeared important as a resistance mechanism only at early season stages, replicate clones of two low lignin progeny plants generally remained resistant to fall armyworm feeding. Mechanical damaging increased resistance to fall armyworm feeding in several of these plants. Degrees of resistance were sometimes associated with leaf form of progeny. These results indicate there are likely multiple insect resistance mechanisms operating at different stages in switchgrass, and that segregation of some mechanisms appears related to growth form of the plants

    MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

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    AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

    Evaluation of the bacterial diversity in the feces of cattle using 16S rDNA bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP)

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    <p>Abstract</p> <p>Background</p> <p>The microbiota of an animal's intestinal tract plays important roles in the animal's overall health, productivity and well-being. There is still a scarcity of information on the microbial diversity in the gut of livestock species such as cattle. The primary reason for this lack of data relates to the expense of methods needed to generate such data. Here we have utilized a bacterial tag-encoded FLX 16s rDNA amplicon pyrosequencing (bTEFAP) approach that is able to perform diversity analyses of gastrointestinal populations. bTEFAP is relatively inexpensive in terms of both time and labor due to the implementation of a novel tag priming method and an efficient bioinformatics pipeline. We have evaluated the microbiome from the feces of 20 commercial, lactating dairy cows.</p> <p>Results</p> <p>Ubiquitous bacteria detected from the cattle feces included <it>Clostridium</it>, <it>Bacteroides, Porpyhyromonas, Ruminococcus, Alistipes, Lachnospiraceae, Prevotella, Lachnospira, Enterococcus, Oscillospira, Cytophage, Anaerotruncus</it>, and <it>Acidaminococcus </it>spp. Foodborne pathogenic bacteria were detected in several of the cattle, a total of 4 cows were found to be positive for <it>Salmonella </it>spp (tentative <it>enterica</it>) and 6 cows were positive for <it>Campylobacter </it>spp. (tentative <it>lanienae</it>).</p> <p>Conclusion</p> <p>Using bTEFAP we have examined the microbiota in the feces of cattle. As these methods continue to mature we will better understand the ecology of the major populations of bacteria the lower intestinal tract. This in turn will allow for a better understanding of ways in which the intestinal microbiome contributes to animal health, productivity and wellbeing.</p

    Design, synthesis, and evaluation of substituted nicotinamide adenine dinucleotide (NAD+) synthetase inhibitors as potential antitubercular agents

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    Nicotinamide adenine dinucleotide (NAD+) synthetase catalyzes the last step in NAD+ biosynthesis. Depletion of NAD+ is bactericidal for both active and dormant Mycobacterium tuberculosis (Mtb). By inhibiting NAD+ synthetase (NadE) from Mtb, we expect to eliminate NAD+ production which will result in cell death in both growing and nonreplicating Mtb. NadE inhibitors have been investigated against various pathogens, but few have been tested against Mtb. Here, we report on the expansion of a series of urea-sulfonamides, previously reported by Brouillette et al. Guided by docking studies, substituents on a terminal phenyl ring were varied to understand the structure-activity-relationships of substituents on this position. Compounds were tested as inhibitors of both recombinant Mtb NadE and Mtb whole cells. While the parent compound displayed very weak inhibition against Mtb NadE (IC50=1000µM), we observed up to a 10-fold enhancement in potency after optimization. Replacement of the 3,4-dichloro group on the phenyl ring of the parent compound with 4-nitro yielded 4f, the most potent compound of the series with an IC50 value of 90µM against Mtb NadE. Our modeling results show that these urea-sulfonamides potentially bind to the intramolecular ammonia tunnel, which transports ammonia from the glutaminase domain to the active site of the enzyme. This hypothesis is supported by data showing that, even when treated with potent inhibitors, NadE catalysis is restored when treated with exogenous ammonia. Most of these compounds also inhibited Mtb cell growth with MIC values of 19-100µg/mL. These results improve our understanding of the SAR of the urea-sulfonamides, their mechanism of binding to the enzyme, and of Mtb NadE as a potential antitubercular drug target
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