Observation Of Turbulent Intermittency Scaling With Magnetic Helicity In An MHD Plasma Wind Tunnel

The intermittency in turbulent magnetic field fluctuations has been observed to scale with the amount of magnetic helicity injected into a laboratory plasma. An unstable spheromak injected into the MHD wind tunnel of the Swarthmore Spheromak Experiment displays turbulent magnetic and plasma fluctuations as it relaxes into a Taylor state. The level of intermittency of this turbulence is determined by finding the flatness of the probability distribution function of increments for magnetic pickup coil fluctuations B(t). The intermittency increases with the injected helicity, but spectral indices are unaffected by this variation. While evidence is provided which supports the hypothesis that current sheets and reconnection sites are related to the generation of this intermittent signal, the true nature of the observed intermittency remains unknown

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.

Modeling the Influence of Energy and Climate Megatrends on Future Costs and Benefits of Marsh Creation in the Mississippi Delta

Over 25% of Mississippi delta (MRDP) wetlands were lost over the past century. There is currently a major effort to restore the MRDP focused on a 50-year time horizon, a period during which the energy system and climate will change dramatically. I modeled hydraulic dredging to sustain marsh from 2016-2066 and 2016-2100 under a range of scenarios for sea level rise, energy price, and management regimes. A marsh elevation model was calibrated to data from MRDP marshes. I developed a model to simulate dredging costs based on the price of crude oil and a project efficiency factor. Crude oil prices were projected using forecasts from global energy models. The costs to sustain marsh between 2016 and 2100 changed from $128,000 ha-1 in the no change scenario to ~$1,010,000 ha-1 in the worst-case scenario in sea level rise and energy price, an ~8-fold increase. Increasing suspended sediment load raised created marsh lifespan and decreased long term dredging costs. Created marsh lifespan changed nonlinearly with dredging fill elevation and suspended sediment level. Costs and benefits of marsh creation can be optimized by adjusting dredging fill elevations based on the local sediment regime. Regardless of management scenario, sustaining the MRDP with hydraulic dredging suffered declining returns on investment due to the convergence of energy and climate. Marsh creation will likely become unaffordable in the mid to late 21st century, especially if river sediment diversions are not constructed before 2030. Planners must take into consideration coupled energy and climate scenarios for long-term risk assessments and adjust restoration goals accordingly

Alternative Buffer-Layers for the Growth of SrBi2Ta2O9 on Silicon

In this work we investigate the influence of the use of YSZ and CeO2/YSZ as insulators for Metal- Ferroelectric-Insulator-Semiconductor (MFIS) structures made with SrBi2Ta2O9 (SBT). We show that by using YSZ only the a-axis oriented Pyrochlore phase could be obtained. On the other hand the use of a CeO2/YSZ double-buffer layer gave a c-axis oriented SBT with no amorphous SiO2 inter- diffusion layer. The characteristics of MFIS diodes were greatly improved by the use of the double buffer. Using the same deposition conditions the memory window could be increased from 0.3 V to 0.9 V. From the piezoelectric response, nano-meter scale ferroelectric domains could be clearly identified in SBT thin films.Comment: 5 pages, 9 figures, 13 refernece

The exact eigenstates of the neutrino mass matrix without CP-phase violation

In this paper we obtain the exact mass-eigenstates of the Majorana physical neutrinos. We start by taking into account a general $3\times3$ mass matrix without any CP-phase violation. It is then diagonalized by exactly solving an appropriate set of equations. The solution supplies straightforwardly the mass eigenvalues depending on the diagonal entries and mixing angles. Finally, the consequences of these analytical expressions are discussed assuming various phenomenological restrictions such as conserving the global lepton number $L=L_{e}-L_{\mu}-L_{\tau}$ and the $\mu-\tau$ interchange symmetry. The minimal absolute mass in the neutrino sector is also obtained since the two plausible scenarios invoked above are employed.Comment: 9 pages, no 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.

The Renormalized Stress Tensor in Kerr Space-Time: Numerical Results for the Hartle-Hawking Vacuum

We show that the pathology which afflicts the Hartle-Hawking vacuum on the Kerr black hole space-time can be regarded as due to rigid rotation of the state with the horizon in the sense that when the region outside the speed-of-light surface is removed by introducing a mirror, there is a state with the defining features of the Hartle-Hawking vacuum. In addition, we show that when the field is in this state, the expectation value of the energy-momentum stress tensor measured by an observer close to the horizon and rigidly rotating with it corresponds to that of a thermal distribution at the Hawking temperature rigidly rotating with the horizon.Comment: 17 pages, 7 figure

Finite Temperature Density Matrix Renormalization using an enlarged Hilbert space

We apply a generalization of the time-dependent DMRG to study finite temperature properties of several quantum spin chains, including the frustrated $J_1-J_2$ model. We discuss several practical issues with the method, including use of quantum numbers and finite size effects. We compare with transfer-matrix DMRG, finding that both methods produce excellent results.Comment: 4 pages and 4 figure

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.