Regulating Rare Disease: Safely Facilitating Access to Orphan Drugs

While approximately one in ten Americans suffers from a rare disease, only 5 percent of rare diseases have a U.S. Food and Drug Administration (FDA) approved treatment. Congressional and regulatory efforts to stimulate the development of rare-disease treatments, while laudable, have not resolved the fundamental issues surrounding rare-disease treatment development. Indeed, small patient populations, incomplete scientific understanding of rare diseases, and high development costs continually limit the availability of rare-disease treatments. To illustrate the struggle of developing and approving safe rare-disease treatments, this Note begins by discussing the approval of Eteplirsen, the first drug approved for treating a rare disease called Duchenne muscular dystrophy. After exploring the current drug regulation system and how this impacts the availability of rare-disease treatments, this Note examines the 21st Century Cures Act’s patient experience data provisions and the currently pending Trickett Wendler Right to Try Act. Ultimately, the unmet therapeutic needs of rare-disease patients can be met while protecting patient safety, this Note reasons that, if carefully implemented, the 21st Century Cures Act and the Trickett Wendler Right to Try Act could work in tandem to safely facilitate patient access to rare-disease treatments

Dynamics of Quantum Noise in a Tunnel Junction under ac Excitation

We report the first measurement of the \emph{dynamical response} of shot noise (measured at frequency $\omega$) of a tunnel junction to an ac excitation at frequency $\omega_0$. The experiment is performed in the quantum regime, $\hbar\omega\sim\hbar\omega_0\gg k_BT$ at very low temperature T=35mK and high frequency $\omega_0/2\pi=6.2$ GHz. We observe that the noise responds in phase with the excitation, but not adiabatically. The results are in very good agreement with a prediction based on a new current-current correlator.Comment: Theory removed. More experimental details. One extra figur

Electronic structure of the Ca3Co4O9\rm Ca_3Co_4O_9 compound from ab initio local interactions

We used fully correlated ab initio calculations to determine the effective parameters of Hubbard and t - J models for the thermoelectric misfit compound $\rm Ca_3Co_4O_9$. As for the $\rm Na_xCoO_2$ family the Fermi level orbitals are the $a_{1g}$ orbitals of the cobalt atoms ; the $e'_g$ being always lower in energy by more than 240\,meV. The electron correlation is found very large $U/t\sim 26$ as well as the parameters fluctuations as a function of the structural modulation. The main consequences are a partial $a_{1g}$ electrons localization and a fluctuation of the in-plane magnetic exchange from AFM to FM. The behavior of the Seebeck coefficient as a function of temperature is discussed in view of the ab initio results, as well as the 496\,K phase transition

Decrypting the cyclotron effect in graphite using Kerr rotation spectroscopy

We measure the far-infrared magneto-optical Kerr rotation and reflectivity spectra in graphite and achieve a highly accurate unified microscopic description of all data in a broad range of magnetic fields by taking rigorously the c-axis band dispersion and the trigonal warping into account. We find that the second- and the forth-order cyclotron harmonics are optically almost as strong as the fundamental resonance even at high fields. They must play, therefore, a major role in magneto-optical and magneto-plasmonic applications based on Bernal stacked graphite and multilayer graphene.Comment: 4 pages, 3 figures + Supplemental Materia

Magneto-optical Kramers-Kronig analysis

We describe a simple magneto-optical experiment and introduce a magneto-optical Kramers-Kronig analysis (MOKKA) that together allow extracting the complex dielectric function for left- and right-handed circular polarizations in a broad range of frequencies without actually generating circularly polarized light. The experiment consists of measuring reflectivity and Kerr rotation, or alternatively transmission and Faraday rotation, at normal incidence using only standard broadband polarizers without retarders or quarter-wave plates. In a common case, where the magneto-optical rotation is small (below $\sim$ 0.2 rad), a fast measurement protocol can be realized, where the polarizers are fixed at 45$^\circ$ with respect to each other. Apart from the time-effectiveness, the advantage of this protocol is that it can be implemented at ultra-high magnetic fields and in other situations, where an \emph{in-situ} polarizer rotation is difficult. Overall, the proposed technique can be regarded as a magneto-optical generalization of the conventional Kramers-Kronig analysis of reflectivity on bulk samples and the Kramers-Kronig constrained variational analysis of more complex types of spectral data. We demonstrate the application of this method to the textbook semimetals bismuth and graphite and also use it to obtain handedness-resolved magneto-absorption spectra of graphene on SiC.Comment: 11 pages, 4 figur

Roots Structure and Development of Austrobaileya scandens (Austrobaileyaceae) and Implications for Their Evolution in Angiosperms

Since the resolution of the ANA grade [Amborellales, Nymphaeales, Austrobaileyales] as sister to all other flowering plants, a few comparative studies of root structure have suggested that some of their anatomical traits could be of importance to understanding root evolutionary development and angiosperm phylogeny. However, there is still a paucity of information on root structure and apical meristems (RAMs) in these lineages and especially the sister to all other Austrobaileyales, Austrobaileya scandens. We used microtome sections and bright field, epifluorescence, laser confocal, and scanning electron microscopy to study adventitious root RAMs and tissues of A. scandens. Our results indicate that root structure is relatively simple in A. scandens. The epidermis has a thick cuticle and lacks root hairs. The stele is typically diarch, or some modification thereof, and surrounded by a cortex differentiated into a uniseriate endodermis, a middle region sometimes packed with starch, some oil cells, and colonized by arbuscular mycorrhizal fungi, and a multiseriate exodermis. Secondary growth produced many vessel elements in the secondary xylem and scattered sclerenchymatous fibers in secondary phloem. The absence of distinct patterning within the RAM and between the RAM and derivative differentiating tissues shows that the RAM is open and characterized by common initials. Roots structure and anatomy of A. scandens are thus essentially similar to some previously described in Amborella or Illicium in the ANA grade and many magnoliids, and suggest that the first woody flowering plants likely had an open RAM with common initials. Their functional and evolutionary significance in woody early-diverging and basal lineages of flowering plants and gymnosperms remains unclear, but they are clearly ancestral traits

Environmental, social, morphological, and behavioral constraints on opportunistic multiple paternity

Peer reviewedPostprin