Nudging the FDA

[Excerpt] The FDA’s regulation of drugs is frequently the subject of policy debate, with arguments falling into two camps. On the one hand, a libertarian view of patients and the health care system holds high the value of consumer choice. Patients should get all the information and the drugs they want; the FDA should do what it can to enforce some basic standards but should otherwise get out of the way. On the other hand, a paternalist view values the FDA’s role as an expert agency standing between patients and a set of potentially dangerous drugs and potentially unscrupulous or at least insufficiently careful drug companies. We lay out here some of the ways the FDA regulates drugs, including some normally left out of the debate, and suggest a middle ground between libertarian and paternalistic approaches focused on correcting information asymmetry and aligning incentives.

A study of the boundary flow in a rocket combustion chamber. Part 3 - Data report Final report

Rocket motor boundary flow sampling apparatu

Surface wind convergence as a short-term predictor of cloud-to-ground lightning at Kennedy Space Center: A four-year summary and evaluation

Since 1986, USAF forecasters at NASA-Kennedy have had available a surface wind convergence technique for use during periods of convective development. In Florida during the summer, most of the thunderstorm development is forced by boundary layer processes. The basic premise is that the life cycle of convection is reflected in the surface wind field beneath these storms. Therefore the monitoring of the local surface divergence and/or convergence fields can be used to determine timing, location, longevity, and the lightning hazards which accompany these thunderstorms. This study evaluates four years of monitoring thunderstorm development using surface wind convergence, particularly the average over the area. Cloud-to-ground (CG) lightning is related in time and space with surface convergence for 346 days during the summers of 1987 through 1990 over the expanded wind network at KSC. The relationships are subdivided according to low level wind flow and midlevel moisture patterns. Results show a one in three chance of CG lightning when a convergence event is identified. However, when there is no convergence, the chance of CG lightning is negligible

The North Atlantic biological pump : insights from the Ocean Observatories Initiative Irminger Sea Array

Author Posting. © The Oceanography Society, 2018. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 31, no. 1 (2018): 42–49, doi:10.5670/oceanog.2018.108.The biological pump plays a key role in the global carbon cycle by transporting photosynthetically fixed organic carbon into the deep ocean, where it can be sequestered from the atmosphere over annual or longer time scales if exported below the winter ventilation depth. In the subpolar North Atlantic, carbon sequestration via the biological pump is influenced by two competing forces: a spring diatom bloom that features large, fast-sinking biogenic particles, and deep winter mixing that requires particles to sink much further than in other ocean regions to escape winter ventilation. We synthesize biogeochemical sensor data from the first two years of operations at the Ocean Observatories Initiative Irminger Sea Array of moorings and gliders (September 2014–July 2016), providing the first simultaneous year-round observations of biological carbon cycling processes in both the surface ocean and the seasonal thermocline in this critical but previously undersampled region. These data show significant mixed layer net autotrophy during the spring bloom and significant respiration in the seasonal thermocline during the stratified season (~5.9 mol C m–2 remineralized between 200 m and 1,000 m). This respired carbon is subsequently ventilated during winter convective mixing (>1,000 m), a significant reduction in potential carbon sequestration. This highlights the importance of year-round observations to accurately constrain the biological pump in the subpolar North Atlantic, as well as other high-latitude regions that experience deep winter mixing.Hilary Palevsky acknowledges support from the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Weston Howland Jr. Postdoctoral Scholarship

Complete Determination of the Pin1 Catalytic Domain Thermodynamic Cycle by NMR Lineshape Analysis

The phosphorylation-specific peptidyl-prolyl isomerase Pin1 catalyzes the isomerization of the peptide bond preceding a proline residue between cis and trans isomers. To best understand the mechanisms of Pin1 regulation, rigorous enzymatic assays of isomerization are required. However, most measures of isomerase activity require significant constraints on substrate sequence and only yield rate constants for the cis isomer, kciscatand apparent Michaelis constants, KAppM . By contrast, NMR lineshape analysis is a powerful tool for determining microscopic rates and populations of each state in a complex binding scheme. The isolated catalytic domain of Pin1 was employed as a first step towards elucidating the reaction scheme of the full-length enzyme. A 24-residue phosphopeptide derived from the amyloid precurser protein intracellular domain (AICD) phosphorylated at Thr668 served as a biologically-relevant Pin1 substrate. Specific 13C labeling at the Pin1-targeted proline residue provided multiple reporters sensitive to individual isomer binding and on-enzyme catalysis. We have performed titration experiments and employed lineshape analysis of phosphopeptide 13C–1H constant time HSQC spectra to determine kciscat , ktranscat , KcisD , and KtransD for the catalytic domain of Pin1 acting on this AICD substrate. The on-enzyme equilibrium value of [E·trans]/[E·cis] = 3.9 suggests that the catalytic domain of Pin1 is optimized to operate on this substrate near equilibrium in the cellular context. This highlights the power of lineshape analysis for determining the microscopic parameters of enzyme catalysis, and demonstrates the feasibility of future studies of Pin1-PPIase mutants to gain insights on the catalytic mechanism of this important enzyme

Assessing the Impact of Infrastructure Projects on Global Sustainable Development Goals

While sustainability of civil infrastructure is critical to professionals, project owners, regulators, funding agencies and the public, little is done to link individual project sustainability to the United Nation’s 17 global sustainable development goals for 2030. This paper provides some answers but also exposes many questions that need resolution by the infrastructure sector. Using empirical evidence, the authors have identified a ‘golden thread’ between best-practice sustainability-reporting frameworks at project level with those at organisational level. In doing so, they find there is sufficient linkage to embed sustainable-development-goal impact targets into the design stage of an infrastructure project. This would provide a more robust investment appraisal at the project design phase, helping to define project success more widely across the triple bottom line of economic, social and environmental outcomes and associated impact

Expanding the therapeutic repertoire of epidermal growth factor receptor blockade: radiosensitization

Expression of epidermal growth factor receptor (EGFR) has been associated with radioresistance in cancer. Moreover, tumour cell recovery after irradiation paradoxically occurs, in part, as a result of activation of EGFR signalling by such treatment. A recent article by Huang, Li, Armstrong and Harari provides strong rationale for considering the anti-EGFR agent ZD1839 ('Iressa') as a radiosensitizing strategy. With the use of several in vitro and xenograft models of human squamous cell head and neck carcinoma, ZD1939 was shown to markedly improve radiotherapeutic response, with superior tumour inhibition and delayed tumour regrowth. Mechanisms underlying this effect included anti-proliferative and pro-apoptotic activity, with significant perturbation of tumour angiogenesis