Medicare beneficiary panel characteristics associated with high Part D biologic disease-modifying anti-rheumatic drug prescribing for older adults among rheumatologists.

ABSTRACT: The aim of this study was to investigate beneficiary panel characteristics associated with rheumatologists' prescribing of biologic DMARDs (bDMARDs) for older adults.In this retrospective observational study, we used Medicare Public Use Files (PUFs) to identify rheumatologists who met criteria for high-prescribing, defined as bDMARD prescription constituting ≥20% of their DMARD claims for beneficiaries ≥65 years of age. We first used descriptive analysis then multivariable regression model to test the association of high prescribing of bDMARDs with rheumatologists' panel size and beneficiary characteristics. In particular, we quantified the proportion of panel beneficiaries ≥75 years of age to assess how caring for an older panel correlate with prescribing of bDMARDs.We identified 3197 unique rheumatologists, of whom 405 (13%) met criteria for high prescribing of bDMARDs for Medicare beneficiaries ≥65 years of age. The high-prescribers provided care to 12% of study older adults, and yet accounted for 21% of bDMARD prescriptions for them. High prescribing of bDMARDs was associated with smaller panel size, and their beneficiaries were more likely to be non-black, ≥75 years of age, non-dual eligible, have diagnosis of CHF, however, less likely to have CKD.Rheumatologists differ in their prescribing of bDMARDs for older adults, and those caring for more beneficiaries ≥75 years of age are more likely to be high-prescribers. Older adults are more prone to the side-effects of bDMARDs and further investigation is warranted to understand drivers of differential prescribing behaviors to optimize use of these high-risk and high-cost medications.http://deepblue.lib.umich.edu/bitstream/2027.42/170715/2/Medicare beneficiary panel characteristics associated with high Part D biologic disease-modifying anti-rheumatic drug prescr.pdfPublished versio

The Tevatron at the Frontier of Dark Matter Direct Detection

Direct detection of dark matter (DM) requires an interaction of dark matter particles with nucleons. The same interaction can lead to dark matter pair production at a hadron collider, and with the addition of initial state radiation this may lead to mono-jet signals. Mono-jet searches at the Tevatron can thus place limits on DM direct detection rates. We study these bounds both in the case where there is a contact interaction between DM and the standard model and where there is a mediator kinematically accessible at the Tevatron. We find that in many cases the Tevatron provides the current best limit, particularly for light dark matter, below 5 GeV, and for spin dependent interactions. Non-standard dark matter candidates are also constrained. The introduction of a light mediator significantly weakens the collider bound. A direct detection discovery that is in apparent conflict with mono-jet limits will thus point to a new light state coupling the standard model to the dark sector. Mono-jet searches with more luminosity and including the spectrum shape in the analysis can improve the constraints on DM-nucleon scattering cross section.Comment: 20 pages, 8 figures, final version in JHE

Rectified voltage induced by a microwave field in a confined two-dimensional electron gas with a mesoscopic static vortex

We investigate the effect of a microwave field on a confined two dimensional electron gas which contains an insulating region comparable to the Fermi wavelength. The insulating region causes the electron wave function to vanish in that region. We describe the insulating region as a static vortex. The vortex carries a flux which is determined by vanishing of the charge density of the electronic fluid due to the insulating region. The sign of the vorticity for a hole is opposite to the vorticity for adding additional electrons. The vorticity gives rise to non-commuting kinetic momenta. The two dimensional electron gas is described as fluid with a density which obeys the Fermi-Dirac statistics. The presence of the confinement potential gives rise to vanishing kinetic momenta in the vicinity of the classical turning points. As a result, the Cartesian coordinate do not commute and gives rise to a Hall current which in the presence of a modified Fermi-Surface caused by the microwave field results in a rectified voltage. Using a Bosonized formulation of the two dimensional gas in the presence of insulating regions allows us to compute the rectified current. The proposed theory may explain the experimental results recently reported by J. Zhang et al.Comment: 14 pages, 2 figure

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Effect of Dietary Components on Larval Life History Characteristics in the Medfly (Ceratitis capitata: Diptera, Tephritidae)

Background: The ability to respond to heterogenous nutritional resources is an important factor in the adaptive radiation of insects such as the highly polyphagous Medfly. Here we examined the breadth of the Medfly’s capacity to respond to different developmental conditions, by experimentally altering diet components as a proxy for host quality and novelty. Methodology/Principal Findings: We tested responses of larval life history to diets containing protein and carbohydrate components found in and outside the natural host range of this species. A 40% reduction in the quantity of protein caused a significant increase in egg to adult mortality by 26.5%±6% in comparison to the standard baseline diet. Proteins and carbohydrates had differential effects on larval versus pupal development and survival. Addition of a novel protein source, casein (i.e. milk protein), to the diet increased larval mortality by 19.4%±3% and also lengthened the duration of larval development by 1.93±0.5 days in comparison to the standard diet. Alteration of dietary carbohydrate, by replacing the baseline starch with simple sugars, increased mortality specifically within the pupal stage (by 28.2%±8% and 26.2%±9% for glucose and maltose diets, respectively). Development in the presence of the novel carbohydrate lactose (milk sugar) was successful, though on this diet there was a decrease of 29.8±1.6 µg in mean pupal weight in comparison to pupae reared on the baseline diet. Conclusions: The results confirm that laboratory reared Medfly retain the ability to survive development through a wide range of fluctuations in the nutritional environment. We highlight new facets of the responses of different stages of holometabolous life histories to key dietary components. The results are relevant to colonisation scenarios and key to the biology of this highly invasive species

Compressibility of titanosilicate melts

The effect of composition on the relaxed adiabatic bulk modulus (K0) of a range of alkali- and alkaline earth-titanosilicate [X 2 n/n+ TiSiO5 (X=Li, Na, K, Rb, Cs, Ca, Sr, Ba)] melts has been investigated. The relaxed bulk moduli of these melts have been measured using ultrasonic interferometric methods at frequencies of 3, 5 and 7 MHz in the temperature range of 950 to 1600°C (0.02 Pa s < s < 5 Pa s). The bulk moduli of these melts decrease with increasing cation size from Li to Cs and Ca to Ba, and with increasing temperature. The bulk moduli of the Li-, Na-, Ca- and Ba-bearing metasilicate melts decrease with the addition of both TiO2 and SiO2 whereas those of the K-, Rb- and Cs-bearing melts increase. Linear fits to the bulk modulus versus volume fraction of TiO2 do not converge to a common compressibility of the TiO2 component, indicating that the structural role of TiO2 in these melts is dependent on the identity of the cation. This proposition is supported by a number of other property data for these and related melt compositions including heat capacity and density, as well as structural inferences from X-ray absorption spectroscopy (XANES). The compositional dependence of the compressibility of the TiO2 component in these melts explains the difficulty incurred in previous attempts to incorporate TiO2 in calculation schemes for melt compressibility. The empirical relationship KV-4/3 for isostructural materials has been used to evaluate the compressibility-related structural changes occurring in these melts. The alkali metasilicate and disilicate melts are isostructural, independent of the cation. The addition of Ti to the metasilicate composition (i.e. X2TiSiO5), however, results in a series of melts which are not isostructural. The alkaline-earth metasilicate and disilicate compositions are not isostructural, but the addition of Ti to the metasilicate compositions (i.e. XTiSiO5) would appear, on the basis of modulus-volume systematics, to result in the melts becoming isostructural with respect to compressibility

WIMP-nucleus scattering in chiral effective theory

We discuss long-distance QCD corrections to the WIMP-nucleon(s) interactions in the framework of chiral effective theory. For scalar-mediated WIMP-quark interactions, we calculate all the next-to-leading-order corrections to the WIMP-nucleus elastic cross-section, including two-nucleon amplitudes and recoil-energy dependent shifts to the single-nucleon scalar form factors. As a consequence, the scalar-mediated WIMP-nucleus cross-section cannot be parameterized in terms of just two quantities, namely the neutron and proton scalar form factors at zero momentum transfer, but additional parameters appear, depending on the short-distance WIMP-quark interaction. Moreover, multiplicative factorization of the cross-section into particle, nuclear and astro-particle parts is violated. In practice, while the new effects are of the natural size expected by chiral power counting, they become very important in those regions of parameter space where the leading order WIMP-nucleus amplitude is suppressed, including the so-called "isospin-violating dark matter" regime. In these regions of parameter space we find order-of-magnitude corrections to the total scattering rates and qualitative changes to the shape of recoil spectra.Comment: 23 pages, 6 figures, 1 tabl

In Vitro Biologic Activities of the Antimicrobials Triclocarban, Its Analogs, and Triclosan in Bioassay Screens: Receptor-Based Bioassay Screens

BackgroundConcerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects.ObjectivesIn this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor-responsive and calcium signaling bioassays.Materials and methodsWe determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor-responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1).ResultsSome carbanilide compounds, including TCC (1-10 muM), enhanced estradiol (E(2))-dependent or testosterone-dependent activation of ER- and AR-responsive gene expression up to 2.5-fold but exhibited little or no agonistic activity alone. Some carbanilides and TCS exhibited weak agonistic and/or antagonistic activity in the AhR-responsive bioassay. TCS exhibited antagonistic activity in both ER- and AR-responsive bioassays. TCS (0.1-10 muM) significantly enhanced the binding of [(3)H]ryanodine to RyR1 and caused elevation of resting cytosolic [Ca(2+)] in primary skeletal myotubes, but carbanilides had no effect.ConclusionsCarbanilides, including TCC, enhanced hormone-dependent induction of ER- and AR-dependent gene expression but had little agonist activity, suggesting a new mechanism of action of endocrine-disrupting compounds. TCS, structurally similar to noncoplanar ortho-substituted poly-chlorinated biphenyls, exhibited weak AhR activity but interacted with RyR1 and stimulated Ca(2+) mobilization. These observations have potential implications for human and animal health. Further investigations are needed into the biological and toxicologic effects of TCC, its analogs, and TCS