Transport calculation of dilepton production at ultrarelativistic energies

Dilepton spectra are calculated within the microscopic transport model UrQMD and compared to data from the CERES experiment. The invariant mass spectra in the region 300 MeV < M < 600 MeV depend strongly on the mass dependence of the $\rho$ meson decay width which is not sufficiently determined by the Vector Meson Dominance model. A consistent explanation of both the recent Pb+Au data and the proton induced data can be given without additional medium effects

Self-diffusion in sheared colloidal suspensions: violation of fluctuation-dissipation relation

Using memory-function formalism we show that in sheared colloidal suspensions the fluctuation-dissipation theorem for self-diffusion, i.e. Einstein's relation between self-diffusion and mobility tensors, is violated and propose a new way to measure this violation in Brownian Dynamics simulations. We derive mode-coupling expressions for the tagged particle friction tensor and for an effective, shear-rate dependent temperature

Opportunities for Improving the Drug Development Process: Results from a Survey of Industry and the FDA

In the United States, the Food and Drug Administration (FDA) agency is responsible for regulating the safety and efficacy of biopharmaceutical drug products. Furthermore, the FDA is tasked with speeding new medical innovations to market. These two missions create an inherent tension within the agency and between the agency and key stakeholders. Oftentimes, communications and interactions between regulated companies and the FDA suffer. The focus of this research is on the interactions between the FDA and the biopharmaceutical companies that perform drug R&D. To assess the current issues and state of communication and interaction between the FDA and industry, we carried out a survey of industry leadership in R&D and regulatory positions as well as senior leadership at the FDA who have responsibility for drug evaluation and oversight. Based on forty-nine industry and eight FDA interviews we conducted, we found that industry seeks additional structured and informal interactions with the FDA, especially during Phase II of development. Overall, industry placed greater value on additional communication than did the FDA. Furthermore, industry interviewees indicated that they were willing to pay PDUFA-like fees during clinical development to ensure that the FDA could hire additional, well-qualified staff to assist with protocol reviews and decision-making. Based on our survey and discussions, we uncovered several thematic opportunities to improve interactions between the FDA and industry and to reduce clinical development times: 1) develop metrics and goals at the FDA for clinical development times in exchange for PDUFA like fees; 2) establish an oversight board consisting of industry, agency officials, and premier external scientists (possibly at NIH or CDC) to evaluate and audit retrospectively completed and terminated drug projects; and 3) construct a knowledge database that can simultaneously protect proprietary data while allowing sponsor companies to understand safety issues and problems of previously developed/failed drug programs. While profound scientific and medical challenges face the FDA and industry, the first step to reducing development times and associated costs and facilitating innovation is to provide an efficient regulatory process that reduces unnecessary uncertainty and delays due to lack of communication and interaction.

Partitioning of energy in highly polydisperse granular gases

A highly polydisperse granular gas is modeled by a continuous distribution of particle sizes, a, giving rise to a corresponding continuous temperature profile, T(a), which we compute approximately, generalizing previous results for binary or multicomponent mixtures. If the system is driven, it evolves towards a stationary temperature profile, which is discussed for several driving mechanisms in dependence on the variance of the size distribution. For a uniform distribution of sizes, the stationary temperature profile is nonuniform with either hot small particles (constant force driving) or hot large particles (constant velocity or constant energy driving). Polydispersity always gives rise to non-Gaussian velocity distributions. Depending on the driving mechanism the tails can be either overpopulated or underpopulated as compared to the molecular gas. The deviations are mainly due to small particles. In the case of free cooling the decay rate depends continuously on particle size, while all partial temperatures decay according to Haff's law. The analytical results are supported by event driven simulations for a large, but discrete number of species.Comment: 10 pages; 5 figure

Assessing the Impacts of the Prescription Drug User Fee Acts (PDUFA) on the FDA Approval Process

Congress enacted and renewed the Prescription Drug User Fee Acts (PDUFA) in 1992, and renewed it in 1997 and 2002, mandating FDA performance goals in reviewing and acting on drug applications within specified time periods. In turn, the FDA was permitted to levy user fees on drug sponsors submitting applications to the FDA. While PDUFA mandated action or review times, its ultimate impacts on actual final drug approval times are unknown. We model and quantify the impact of PDUFA-I and II on drug approval times, since these approval dates are the ones most directly related to new medicines becoming available to benefit patients. In assessing the impacts of PDUFA on drug approval times, it is noteworthy that approval times were trending downwards at 1.7% percent per year prior to implementation of PDUFA. Assuming continuation of that time trend, approval times post-PDUFA would have fallen even in the absence of PDUFA. Our principal finding is that PDUFA accelerated this downward trend so that instead of a counterfactual 6% reduction in approval times from 24.2 to 20.4 months in absence of these acts between 1991 and 2002, there was an observed decline of about 42%, from 24.2 to 14.2 months, following implementation of PDUFA. Thus, of the total observed decline in approval times between 1991 and 2002, approximately two-thirds can be attributed to PDUFA. However, much of this impact occurred in the initial years between 1992 and 1997 (PDUFA-I) rather than during the subsequent 1997-2002 time frame (PDUFA-II). We discuss implications of these findings and how future research might quantify the social value of the observed acceleration in the FDA drug approvals.

Assessing the Safety and Efficacy of the FDA: The Case of the Prescription Drug User Fee Acts

The US Food and drug Administration (FDA) is estimated to regulate markets accounting for about 20% of consumer spending in the US. This paper proposes a general methodology to evaluate FDA policies, in general, and the central speed-safety tradeoff it faces, in particular. We apply this methodology to estimate the welfare effects of a major piece of legislation affecting this tradeoff, the Prescription Drug User Fee Acts (PDUFA). We find that PDUFA raised the private surplus of producers, and thus innovative returns, by about $11 to$13 billion. Dependent on the market power assumed of producers while having patent protection, we find that PDUFA raised consumer welfare between $5 to$19 billion; thus the combined social surplus was raised between $18 to$31 billions. Converting these economic gains into equivalent health benefits, we find that the more rapid access of drugs on the market enabled by PDUFA saved the equivalent of 180 to 310 thousand life-years. Additionally, we estimate an upper bound on the adverse effects of PDUFA based on drugs submitted during PDUFA I/II and subsequently withdrawn for safety reasons, and find that an extreme upper bound of about 56 thousand life-years were lost. We discuss how our general methodology could be used to perform a quantitative and evidence-based evaluation of the desirability of other FDA policies in the future, particularly those affecting the speed-safety tradeoff.

Attentional avoidance of high-fat food in unsuccessful dieters

Using the exogenous cueing task, this study examined whether restrained and disinhibited eaters differ in their orientation of attention towards and their difficulty to disengage from high versus low-fat food pictures in a relatively short (500 ms) and a long presentation format (1500 ms). Overall, participants in the 500 ms condition showed a tendency to direct attention away from high-fat food pictures compared to neutral pictures. No differential pattern was evident for the 1500 ms condition. Correlational analysis revealed that reduced engagement with high-fat food was particularly pronounced for disinhibited eaters. Although in the short term this seems an adaptive strategy, it may eventually become counterproductive, as it could hinder habituation and learning to cope with seductive characteristics of high-fat food. (C) 2010 Elsevier Ltd. All rights reserved