Medicine Goes Madison Avenue: An Evaluation of the Effect of Direct-to-Consumer Pharmaceutical Advertising on the Learned Intermediary Doctrine

This comment will attempt to examine and evaluate the learned intermediary doctrine in light of the recent explosion in direct-to-consumer advertising of pharmaceutical products, focusing on an analysis of product liability principles, including comments from the proposed Restatement (Third) of Torts, as they apply to this subject. This comment will examine the potential ramification of FDA consumer advertising requirements, especially as they relate to potential additional exceptions to the learned intermediary doctrine. This analysis will support the conclusion that the learned intermediary doctrine remains functional and provides the consumer with the best available alternative to ensure the most appropriate use of safe and effective pharmaceuticals

Medicine Goes Madison Avenue: An Evaluation of the Effect of Direct-to-Consumer Pharmaceutical Advertising on the Learned Intermediary Doctrine

This comment will attempt to examine and evaluate the learned intermediary doctrine in light of the recent explosion in direct-to-consumer advertising of pharmaceutical products, focusing on an analysis of product liability principles, including comments from the proposed Restatement (Third) of Torts, as they apply to this subject. This comment will examine the potential ramification of FDA consumer advertising requirements, especially as they relate to potential additional exceptions to the learned intermediary doctrine. This analysis will support the conclusion that the learned intermediary doctrine remains functional and provides the consumer with the best available alternative to ensure the most appropriate use of safe and effective pharmaceuticals

Effects of CO2-induced pH reduction on the exoskeleton structure and biophotonic properties of the shrimp Lysmata californica.

The anticipated effects of CO2-induced ocean acidification on marine calcifiers are generally negative, and include dissolution of calcified elements and reduced calcification rates. Such negative effects are not typical of crustaceans for which comparatively little ocean acidification research has been conducted. Crustaceans, however, depend on their calcified exoskeleton for many critical functions. Here, we conducted a short-term study on a common caridean shrimp, Lysmata californica, to determine the effect of CO2-driven reduction in seawater pH on exoskeleton growth, structure, and mineralization and animal cryptic coloration. Shrimp exposed to ambient (7.99 ± 0.04) and reduced pH (7.53 ± 0.06) for 21 days showed no differences in exoskeleton growth (percent increase in carapace length), but the calcium weight percent of their cuticle increased significantly in reduced pH conditions, resulting in a greater Ca:Mg ratio. Cuticle thickness did not change, indicating an increase in the mineral to matrix ratio, which may have mechanical consequences for exoskeleton function. Furthermore, there was a 5-fold decrease in animal transparency, but no change in overall shrimp coloration (red). These results suggest that even short-term exposure to CO2-induced pH reduction can significantly affect exoskeleton mineralization and shrimp biophotonics, with potential impacts on crypsis, physical defense, and predator avoidance

Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy.

Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles) involved in AR expression and their possible role as therapeutic targets

Abraham Lincoln as a Man of Ideas

Abraham Lincoln was a skilled politician, an inspirational leader, and a man of humor and pathos. What many may not realize is how much he was also a man of ideas. Despite the most meager of formal educations, Lincoln’s tremendous intellectual curiosity drove him into the circle of Enlightenment philosophy and democratic political ideology. And from these, Lincoln developed a set of political convictions that guided him throughout his life and his presidency. Abraham Lincoln as a Man of Ideas, a compilation of ten essays from Lincoln scholar, Allen C. Guelzo, uncovers the hidden sources of Lincoln’s ideas and examines the beliefs that directed his career and brought an end to slavery and the Civil War. These essays reveal Lincoln to be a man of impressive intellectual probity and depth as well as a man of great contradictions. He was an apostle of freedom who did not believe in human free will; a champion of the Constitution who had to step outside of it in order to save it; a man of many acquaintances and admirers, but few friends; a man who opposed slavery but also opposed the abolition of it; a man of prudence who took more political risks than any other president. Guelzo explores the many faces of Lincoln’s ideas, and especially the influence of the Founding Fathers and the great European champions of democracy. And he links the 16th president’s struggles with the issues of race, emancipation, religion, and civil liberties to the challenges these issues continue to offer to Americans today. Lincoln played many roles in his life—lawyer, politician, president—but in each he was driven by a core of values, convictions, and beliefs about economics, society, and democracy. Abraham Lincoln as a Man of Ideas is a broad and exciting survey of the ideas that made Lincoln great, just as we celebrate the bicentennial his birth. [From the publisher]https://cupola.gettysburg.edu/books/1006/thumbnail.jp

Cryogenic Curation: Isolated Technology and Mission Operational Requirements for Sample Return

Future lunar, Mars, asteroid, and comet sample return missions may collect samples that have been preserved at sub-freezing or even cryogenic temperatures. For such samples, the study of volatiles and temperature-sensitive minerals will have high priority. Valuable geochemical and mineralogical information will be lost if such samples are allowed to reach ambient temperatures on Earth. The ability to store, document, subdivide, and transport extraterrestrial geologic samples while maintaining sub-freezing or cryogenic temperatures, possibly as low as 40 K, is required for the complete scientific study of samples from cold environments

Cryogenic Curation of Lunar Samples Returned to Earth

Future lunar missions may collect samples that have been preserved at sub-freezing or even cryogenic temperatures. For such samples, the study of volatiles and temperature-sensitive minerals will have high priority. Valuable geochemical and mineralogical information will be lost if such samples are allowed to reach ambient temperatures on Earth. The ability to store, document, subdivide, and transport extraterrestrial geologic samples while maintaining sub-freezing or cryogenic temperatures, possibly as low as 40 K, is required for the complete scientific study of samples from cold environments. A lunar cryogenic sample return mission might require a combination of passive cooling during collection and cruise and active cooling during and after re-entry for maintaining desired temperatures. Once on Earth, cryocontainment must be maintained through delivery to a cryogenic chamber in the curatorial facility. This cryogenic curation chamber would include cameras and robotic manipulators for preliminary examination, subdivision of samples, and specialized sample allocation containers for shipment to laboratories world-wide. This presentation describes the planning and feasibility of cryogenic curation with current technologies developed for the superconductor industry. In addition, significant advanced research and development would be required to tailor some of these technologies to the task of sample return and long term curation of lunar samples at low temperatures in order to preserve their scientific integrity

Temporal Trends in Human Vulnerability to Excessive Heat

Over recent decades, studies have examined various morbidity and mortality outcomes associated with heat exposure. This review explores the collective knowledge of the temporal trends of heat on human health, with regard to the hypothesis that humans are less vulnerable to heat events presently than in the past. Using Web of Science and Scopus, the authors identified all peer-reviewed articles that contained keywords on human impact (e.g. mortality, morbidity) and meteorological component (e.g. heat, heatwave). After sorting, a total of 71 articles, both case studies and epidemiological studies, contained explicit assessments of temporal trends in human vulnerability, and thus were used in this review. Most of the studies utilized mortality data, focused on the developed world, and showed a general decrease in heat sensitivity. Factors such as the implementation of a heat warning system, increased awareness, and improved quality of life were cited as contributing factors that led to the decreased impact of heat. Despite the overall recent decreases in heat vulnerability, spatial variability was shown, and differences with respect to health outcomes were also discussed. Several papers noted increases in heat\u27s impact on human health, particularly when unprecedented conditions occurred. Further, many populations, from outdoor workers to rural residents, in addition to the populations in much of the developing world, have been significantly underrepresented in research to date, and temporal changes in their vulnerability should be assessed in future studies. Moreover, continued monitoring and improvement of heat intervention is needed; with projected changes in the frequency, duration, and intensity of heat events combined with shifts in demographics, heat will remain a major public health issue moving forward