\u3ci\u3eUnited States v. Caronia\u3c/i\u3e: Off-Label Drug Promotion and First Amendment Balancing

Off-label drug promotion is commonplace in the United States, but it is not without its dangers. While the Food, Drug, and Cosmetic Act does not explicitly ban off-label promotion, the Food & Drug Administration (FDA)— in order to protect consumers from unsafe and ineffective drugs—has taken steps to regulate it. The FDA does so through its intended-use regulation, which lists the types of evidence the FDA can consider in determining whether a drug is misbranded. It is a crime to sell a misbranded drug into interstate commerce or to conspire to do so. On September 25, 2015, the FDA proposed an amendment to the regulation, which has drawn opposition from various industry groups due to its potential to restrict the type of speech that is often used in off-label promotion. The First Amendment challenge to the proposed amendment rests on United States v. Caronia, in which the FDA was prevented from using truthful, nonmisleading speech to convict a pharmaceutical representative of a conspiracy to sell a misbranded drug. This Note examines whether the amendment to the regulation is permissible under Caronia. It first contends that the regulation does not facially violate the First Amendment. It further argues that the rule is constitutional and does not pose the same First Amendment issue as was seen in Caronia as long as the FDA implements it with care. This Note concludes by exploring various ways that the FDA can constitutionally regulate off-label drug promotion under the proposed rule

Nuclear Magnetohydrodynamic EMP, Solar Storms, and Substorms

In addition to a fast electromagnetic pulse (EMP), a high altitude nuclear burst produces a relatively slow magnetohydrodynarnic EMP (MHD EMP), whose effects are like those from solar storm geomagnetically induced currents (SS GIC). The MHD EMP electric field E < 10^-1 V/m and lasts < 10^2 sec, whereas for solar storms E > 10^-2 V/m and lasts >10^3 sec. Although the solar storm electric field is lower than MHD EMP, the solar storm effects are generally greater due to their much longer duration. Substorms produce much smaller effects than SS GIC, but occur much more frequently. This paper describes the physics of such geomagnetic disturbances and analyzes their effects.Comment: 29 pages, 14 figures, 5 table

Short-term variability of a sample of 29 trans-Neptunian objects and Centaurs

We present results of 6 years of observations, reduced and analyzed with the same tools in a systematic way. We report completely new data for 15 objects, for 5 objects we present a new analysis of previously published results plus additional data and for 9 objects we present a new analysis of data already published. Lightcurves, possible rotation periods and photometric amplitudes are reported for all of them. The photometric variability is smaller than previously thought: the mean amplitude of our sample is 0.1mag and only around 15% of our sample has a larger variability than 0.15mag. The smaller variability than previously thought seems to be a bias of previous observations. We find a very weak trend of faster spinning objects towards smaller sizes, which appears to be consistent with the fact that the smaller objects are more collisionally evolved, but could also be a specific feature of the Centaurs, the smallest objects in our sample. We also find that the smaller the objects, the larger their amplitude, which is also consistent with the idea that small objects are more collisionally evolved and thus more deformed. Average rotation rates from our work are 7.5h for the whole sample, 7.6h for the TNOs alone and 7.3h for the Centaurs. All of them appear to be somewhat faster than what one can derive from a compilation of the scientific literature and our own results. Maxwellian fits to the rotation rate distribution give mean values of 7.5h (for the whole sample) and 7.3h (for the TNOs only). Assuming hydrostatic equilibrium we can determine densities from our sample under the additional assumption that the lightcurves are dominated by shape effects, which is likely not realistic. The resulting average density is 0.92g/cm^3 which is not far from the density constraint that one can derive from the apparent spin barrier that we observe.Comment: Accepted for publication in A&

Hermite-Fejér-Related Interpolation and Product Integration

AbstractConvergence of product integration rules based on Hermite-Fejér interpolation with end conditions is shown for all Riemann-integrable functions when the interpolation points are zeros of generalized Jacobi polynomials even in cases where the corresponding Hermite-Fejér operator is indefinite

Adaptive control and parameter identification

The broad theory of adaptive control is introduced, with m o t i v a t i o n for using such techniques. The two mos t popu l a r techniques, the Model Re f er e n c e A d a ptive C o n t r o l l e r s (MRAC) and the Self Tuning C o n t r o l l e r s (STC) are studied in more d e t a i l . The MRAC and the STC often lead to identical solutions. The c on d i t i o n s for which these two techni q u e s are e q u i v a l e n t are discussed. P a r a m e t e r Adap t a ti o n A l go r i t h m s (PAA) are required by both the MRA a n : the STC. For this reason the PAA is e x a m i ne d in some det.ai . This is i n itiated by de r i v i ng an o f f - l i n e lea; -squares PAA. This is then c o n v e r t e d into a r ec u r s i v e on-l in e estimator. Using intuitive arguments, the various choices of gain p a r a m e t e r as well as the v a r ia t i o n s of the nasic form o f the a l g o r i t h m are discussed. This i n c l ud e s a w a r n in g as to w here the p i tf a l l s of such a l g o r i t h m s may lie. In order to examine the s t a b il i t y of these a lgorithms, the H y p e r s t a b i l i t y theorem is introduced. This requires k n o w l e d g e of the Popov i n e q ua l i t y and Stric t l y P o s itive Real (SPR) functions. This is intro d u c ed initially using i n t u i t i v e ene i g y concepts after which the r i g o r ou s m a t h e m a t i c a l representa* ion is d e r i v e d . The H y p e r s t a b i l i t y T h e o r e m is then used to exam i n e the s t a b i l i t y condition for various forms of the PAA