After Caronia: First Amendment Concerns in Off-Label Promotion

The government has successfully prosecuted pharmaceutical companies for off-label promotion of drugs, maintaining that such promotion impermissibly undermines the FDA’s premarket approval process and jeopardizes the public health. In several recent cases, however, pharmaceutical companies have alleged that regulations prohibiting such promotion are unconstitutional because off-label promotion is protected under the First Amendment. Two recent U.S. Supreme Court cases contain language that gives broad protection to advertising and marketing in the pharmaceutical field. This Article questions the reach of these cases as applied to the practice of off-label promotion through detailing

Regulating the NCAA: Making the Calls under the Sherman Antitrust Act and Title IX

The National Collegiate Athletic Association (NCAA) is a powerful force in shaping the intercollegiate athletic programs of some 1200 public and private colleges. Courts have recognized the NCAA as an entity that serves the important and admirable functions of maintaining the amateur status of intercollegiate athletics and the integrity of the educational process for the student-athlete, while providing a fair and equitable competitive environment. Most of the NCAA\u27s rules and regulations are promulgated to promote and maintain these goals. Nevertheless, both student-athletes and coaches have challenged NCAA rules in the courts, claiming that certain rules discriminate on the basis of sex, race, and disability or that the rules place an unreasonable restraint on trade. Courts have struggled with how to apply the laws of the business world as well as civil rights laws to the organization. Two recent decisions have shed some light on the NCAA\u27s status with regard to the reach of federal regulation. In Law v. NCAA, the Tenth Circuit Court of Appeals held that an NCAA rule that restricted the salary of certain Division I basketball coaches violated the Sherman Antitrust Act. The Supreme Court denied certiorari, and the controversy has ended with the NCAA paying 54.5 million dollars to the 2000 coaches who made up the plaintiff class. NCAA v. Smith involved both Sherman Antitrust and Title IX Claims. The plaintiff, a female student-athlete, challenged an NCAA Bylaw that prohibited her from playing college varsity volleyball as a graduate student. The Bylaw, she claimed, violated both the Sherman Antitrust Act and Title IX of the Educational Amendments Act of 1972. The Supreme Court denied certiorari on Smith\u27s antitrust claim and held that the NCAA was not subject to Title IX on the theories presented by Smith because the NCAA is not a recipient of federal funds within the meaning of Title IX. Despite the apparent victory for the NCAA on the Title IX claim, substantial questions about the NCAA\u27s status as a recipient of financial funds and its required compliance with Title IX and other antidiscrimination laws remain. The decision of the Court of Appeals for the Tenth Circuit in Law v. NCAA and that of the Court of Appeals for the Third Circuit in Smith v. NCAA follow previous Supreme Court and federal court decisions in applying antitrust law and analysis to NCAA rules and clarify the Sherman Act\u27s relationship to the NCAA. The Supreme Court\u27s decision in NCAA v. Smith, however, leaves several questions unresolved and unclear regarding Title IX\u27s application to NCAA rules. This Article will discuss the recent antitrust challenges to NCAA rules as well as recent claims that NCAA rules violate civil rights laws. It will focus on how the decisions of the courts of appeals in Smith v. NCAA and Law v. NCAA, with the benefit of the Supreme Court\u27s decision in NCAA v. Board of Regents of University of Oklahoma, illustrate the boundaries of NCAA role making within the constraints of the Sherman Act. It will discuss the Supreme Court\u27s Title IX analysis in Smith, the unclear precedent on which the decision rests, and will develop theories for holding the NCAA accountable under federal antidiscrimination laws

The Myth of Carbon Offsets

The RCRC’s mandate is to help identify and incubate fiscal, monetary, and financial regulatory policy solutions that will put the United States on track for net-zero emissions before 2050. Informed by the work of many scientists, regulators, climate advocates, and international organizations, we take a broadly critical view of the many carbon credit markets and offsetting strategies that have developed thus far and urge policymakers, firms, and other organizations to reevaluate and refine this approach. This paper discusses some of the foundational challenges associated with the practice of offsetting and presents recommendations to chart an alternative path forward

Towards an Understanding of Changing-Look Quasars: An Archival Spectroscopic Search in SDSS

The uncertain origin of the recently-discovered `changing-looking' quasar phenomenon -- in which a luminous quasar dims significantly to a quiescent state in repeat spectroscopy over ~10 year timescales -- may present unexpected challenges to our understanding of quasar accretion. To better understand this phenomenon, we take a first step to building a sample of changing-look quasars with a systematic but simple archival search for these objects in the Sloan Digital Sky Survey Data Release 12. By leveraging the >10 year baselines for objects with repeat spectroscopy, we uncover two new changing-look quasars, and a third discovered previously. Decomposition of the multi-epoch spectra and analysis of the broad emission lines suggest that the quasar accretion disk emission dims due to rapidly decreasing accretion rates (by factors of >2.5), while disfavoring changes in intrinsic dust extinction for the two objects where these analyses are possible. Broad emission line energetics also support intrinsic dimming of quasar emission as the origin for this phenomenon rather than transient tidal disruption events or supernovae. Although our search criteria included quasars at all redshifts and transitions from either quasar-like to galaxy-like states or the reverse, all of the clear cases of changing-look quasars discovered were at relatively low-redshift (z ~ 0.2 - 0.3) and only exhibit quasar-like to galaxy-like transitions.Comment: 15 pages, 8 figures. Updated to accepted versio

miQC : An adaptive probabilistic framework for quality control of single-cell RNA-sequencing data

Single-cell RNA-sequencing (scRNA-seq) has made it possible to profile gene expression in tissues at high resolution. An important preprocessing step prior to performing downstream analyses is to identify and remove cells with poor or degraded sample quality using quality control (QC) metrics. Two widely used QC metrics to identify a 'low-quality' cell are (i) if the cell includes a high proportion of reads that map to mitochondrial DNA (mtDNA) encoded genes and (ii) if a small number of genes are detected. Current best practices use these QC metrics independently with either arbitrary, uniform thresholds (e.g. 5%) or biological context-dependent (e.g. species) thresholds, and fail to jointly model these metrics in a data-driven manner. Current practices are often overly stringent and especially untenable on certain types of tissues, such as archived tumor tissues, or tissues associated with mitochondrial function, such as kidney tissue [1]. We propose a data-driven QC metric (miQC) that jointly models both the proportion of reads mapping to mtDNA genes and the number of detected genes with mixture models in a probabilistic framework to predict the low-quality cells in a given dataset. We demonstrate how our QC metric easily adapts to different types of single-cell datasets to remove low-quality cells while preserving high-quality cells that can be used for downstream analyses. Our software package is available at https://bioconductor.org/packages/miQC. Author summary We developed the miQC package to predict the low-quality cells in a given scRNA-seq dataset by jointly modeling both the proportion of reads mapping to mitochondrial DNA (mtDNA) genes and the number of detected genes using mixture models in a probabilistic framework. We demonstrate how our QC metric easily adapts to different types of single-cell datasets to remove low-quality cells while preserving high-quality cells that can be used for downstream analyses.Peer reviewe

Indicators of Intrinsic AGN Luminosity: a Multi-Wavelength Approach

We consider five indicators for intrinsic AGN luminosity: the luminosities of the [OIII]$\lambda$5007 line, the [OIV]25.89$\mu$m line, the mid-infrared (MIR) continuum emission by the torus, and the radio and hard X-ray (E $>$ 10keV) continuum emission. We compare these different proxies using two complete samples of low-redshift type 2 AGN selected in a homogeneous way based on different indicators: an optically selected [OIII] sample and a mid-infrared selected 12$\mu$m sample. We examine the correlations between all five different proxies, and find better agreement for the [OIV], MIR, and [OIII] luminosities than for the hard X-ray and radio luminosities. Next, we compare the ratios of the fluxes of the different proxies to their values in unobscured Type 1 AGN. The agreement is best for the ratio of the [OIV] and MIR fluxes, while the ratios of the hard X-ray to [OIII], [OIV], and MIR fluxes are systematically low by about an order-of-magnitude in the Type 2 AGN, indicating that hard X-ray selected samples do not represent the full Type 2 AGN population. In a similar spirit, we compare different optical and MIR diagnostics of the relative energetic contributions of AGN and star formation processes in our samples of Type 2 AGN. We find good agreement between the various diagnostic parameters, such as the equivalent width of the MIR polycyclic aromatic hydrocarbon features, the ratio of the MIR [OIV]/[NeII] emission-lines, the spectral index of the MIR continuum, and the commonly used optical emission-line ratios. Finally, we test whether the presence of cold gas associated with star-formation leads to an enhanced conversion efficiency of AGN ionizing radiation into [OIII] or [OIV] emission. We find that no compelling evidence exists for this scenario for the luminosities represented in this sample (L$_{bol}$ $\approx$ 10$^{9}$ - 8 $\times$ 10$^{11}$ L_{\sun}). (abridged)Comment: accepted for publication in ApJ; 58 page

Speech Communication

Contains reports on five research projects.C.J. Lebel FellowshipNational Institutes of Health (Grant 5 T32 NS07040)National Institutes of Health (Grant 5 R01 NS04332)National Science Foundation (Grant 1ST 80-17599)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0254)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0341)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0290

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio