From a Constitutional Right to a Policy of Exceptions: Abigail Alliance and the Future of Access to Experimental Therapy

Although there has been considerable attention to the plight of terminally ill patients with highly sympathetic constitutional and contractual claims that they should be permitted access to unapproved drugs, courts have been appropriately reluctant to grant such claims. Congress and administrative agencies have the requisite institutional competence to decide complex policy issues related to science and health care such as those involved in establishing an expanded access program. Congress and FDA should allow only limited access to unapproved therapies because there are significant concerns about the safety and efficacy of unapproved drugs. Moreover, many of the proposals to widen access may cause delays to the approval process and increased health care costs that are unlikely to be borne in our current climate. Accordingly, we propose limiting access outside of clinical trials, but expanding eligibility for clinical trials in order to ensure that people receive access in a controlled and systematic manner

First-principles calculation of the temperature dependence of the optical response of bulk GaAs

A novel approach has been developed to calculate the temperature dependence of the optical response of a semiconductor. The dielectric function is averaged over several thermally perturbed configurations that are extracted from molecular dynamic simulations. The calculated temperature dependence of the imaginary part of the dielectric function of GaAs is presented in the range from 0 to 700 K. This approach that explicitly takes into account lattice vibrations describes well the observed thermally-induced energy shifts and broadening of the dielectric function.Comment: 6 pages, 3 figure

Absence of quantum-confined Stark effect in GaN quantum disks embedded in (Al,Ga)N nanowires grown by molecular beam epitaxy

Several of the key issues of planar (Al,Ga)N-based deep-ultraviolet light emitting diodes could potentially be overcome by utilizing nanowire heterostructures, exhibiting high structural perfection and improved light extraction. Here, we study the spontaneous emission of GaN/(Al,Ga)N nanowire ensembles grown on Si(111) by plasma-assisted molecular beam epitaxy. The nanowires contain single GaN quantum disks embedded in long (Al,Ga)N nanowire segments essential for efficient light extraction. These quantum disks are found to exhibit intense emission at unexpectedly high energies, namely, significantly above the GaN bandgap, and almost independent of the disk thickness. An in-depth investigation of the actual structure and composition of the nanowires reveals a spontaneously formed Al gradient both along and across the nanowire, resulting in a complex core/shell structure with an Al deficient core and an Al rich shell with continuously varying Al content along the entire length of the (Al,Ga)N segment. This compositional change along the nanowire growth axis induces a polarization doping of the shell that results in a degenerate electron gas in the disk, thus screening the built-in electric fields. The high carrier density not only results in the unexpectedly high transition energies, but also in radiative lifetimes depending only weakly on temperature, leading to a comparatively high internal quantum efficiency of the GaN quantum disks up to room temperature.Comment: This document is the unedited Author's version of a Submitted Work that was subsequently accepted for publication in Nano Letters (2019), copyright (C) American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/acs.nanolett.9b01521, the supporting information is available (free of charge) under the same lin

Identification and quantification of microplastics in wastewater using focal plane array-based reflectance micro-FT-IR imaging

Microplastics (<5 mm) have been documented in environmental samples on a global scale. While these pollutants may enter aquatic environments via wastewater treatment facilities, the abundance of microplastics in these matrices has not been investigated. Although efficient methods for the analysis of microplastics in sediment samples and marine organisms have been published, no methods have been developed for detecting these pollutants within organic-rich wastewater samples. In addition, there is no standardized method for analyzing microplastics isolated from environmental samples. In many cases, part of the identification protocol relies on visual selection before analysis, which is open to bias. In order to address this, a new method for the analysis of microplastics in wastewater was developed. A pretreatment step using 30% hydrogen peroxide (H2O2) was employed to remove biogenic material, and focal plane array (FPA)-based reflectance micro-Fourier-transform (FT-IR) imaging was shown to successfully image and identify different microplastic types (polyethylene, polypropylene, nylon-6, polyvinyl chloride, polystyrene). Microplastic-spiked wastewater samples were used to validate the methodology, resulting in a robust protocol which was nonselective and reproducible (the overall success identification rate was 98.33%). The use of FPA-based micro-FT-IR spectroscopy also provides a considerable reduction in analysis time compared with previous methods, since samples that could take several days to be mapped using a single-element detector can now be imaged in less than 9 h (circular filter with a diameter of 47 mm). This method for identifying and quantifying microplastics in wastewater is likely to provide an essential tool for further research into the pathways by which microplastics enter the environment.This work is funded by a NERC (Natural Environment Research Council) CASE studentship (NE/K007521/1) with contribution from industrial partner Fera Science Ltd., United Kingdom. The authors would like to thank Peter Vale, from Severn Trent Water Ltd, for providing access to and additionally Ashley Howkins (Brunel University London) for providing travel and assistance with the sampling of the Severn Trent wastewater treatment plant in Derbyshire, UK. We are grateful to Emma Bradley and Chris Sinclair for providing helpful suggestions for our research

Seasonal SIMS δ18O record in Astarte borealis from the Baltic Sea tracks a modern regime shift in the NAO

IntroductionAstarte borealis holds great potential as an archive of seasonal paleoclimate, especially due to its long lifespan (several decades to more than a century) and ubiquitous distribution across high northern latitudes. Furthermore, recent work demonstrates that the isotope geochemistry of the aragonite shell is a faithful proxy of environmental conditions. However, the exceedingly slow growth rates of A. borealis in some locations (&lt;0.2mm/year) make it difficult to achieve seasonal resolution using standard micromilling techniques for conventional stable isotope analysis. Moreover, oxygen isotope (δ18O) records from species inhabiting brackish environments are notoriously difficult to use as paleoclimate archives because of the simultaneous variation in temperature and δ18Owater values.MethodsHere we use secondary ion mass spectrometry (SIMS) to microsample an A. borealis specimen from the southern Baltic Sea, yielding 451 SIMS δ18Oshell values at sub-monthly resolution.ResultsSIMS δ18Oshell values exhibit a quasi-sinusoidal pattern with 24 local maxima and minima coinciding with 24 annual growth increments between March 1977 and the month before specimen collection in May 2001.DiscussionAge-modeled SIMS δ18Oshell values correlate significantly with both in situ temperature measured from shipborne CTD casts (r2 = 0.52, p&lt;0.001) and sea surface temperature from the ORAS5-SST global reanalysis product for the Baltic Sea region (r2 = 0.42, p&lt;0.001). We observe the strongest correlation between SIMS δ18Oshell values and salinity when both datasets are run through a 36-month LOWESS function (r2 = 0.71, p &lt; 0.001). Similarly, we find that LOWESS-smoothed SIMS δ18Oshell values exhibit a moderate correlation with the LOWESS-smoothed North Atlantic Oscillation (NAO) Index (r2 = 0.46, p&lt;0.001). Change point analysis supports that SIMS δ18Oshell values capture a well-documented regime shift in the NAO circa 1989. We hypothesize that the correlation between the SIMS δ18Oshell time series and the NAO is enhanced by the latter’s influence on the regional covariance of water temperature and δ18Owater values on interannual and longer timescales in the Baltic Sea. These results showcase the potential for SIMS δ18Oshell values in A. borealis shells to provide robust paleoclimate information regarding hydroclimate variability from seasonal to decadal timescales

Fungal diversity of selected habitat specific Cynorkis species (Orchidaceae) in the central highlands of Madagascar

About 90% of Cynorkis species are endemic to the biodiversity hotspot of Madagascar. This terrestrial habitat-specific genus received little study for fungal diversity to support conservation. We evaluated the diversity of culturable fungi of 11 species and soil characteristics from six sites spanning a >40 km radius in and along the region’s inselbergs. Peloton-forming fungi were grown in vitro from root/protocorm slices and positively identified using DNA sequencing. The fungal diversity was then correlated with soil pH, NO3-N, P, and K. All species harbored either putative mycorrhizal associates in the Rhizoctonia complex or Hypocreales fungi. Tulasnella Operational Taxonomic Units (OTUs) were most prevalent in all soil types while Serendipita OTUs were found in species inhabiting granite/rock outcrops in moist soil (seepage areas). Most Cynorkis species were present in soil with low NO3-N and P levels with diversity of mycorrhizal fungi inversely correlated to NO3-N levels. Of the different orchid life stages sampled, only one species (Cynorkis fastigiata) yielded putative mycorrhizal fungi from juvenile stages. As diversity of mycorrhizal fungi of Cynorkis spp. was negatively correlated with NO3-N, and majority of the studied taxa were found in soils with low NO3-N and P contents, reintroduction studies must include analysis of N and P in detail. For the first time, we showed that the assemblage of culturable fungi in the roots of habitat-specific species of Cynorkis (Orchidaceae) are intimately tied to specific soil characteristics

Cultic resilience and inter-city engagement at the dawn of urban history: protohistoric Mesopotamia and the ‘city seals’, 3200-2750 BC

Within the context of early urbanism, elite groups developed the world’s earliest writing in Mesopotamia, 3200-2750 BC, comprising administrative documents in the form of inscribed clay tablets. How did these proto-literate urban communities engage with each other and what strategies did they employ to address major challenges to their survival? The ‘city seal’ evidence survives as seal impressions on clay bureaucratic artefacts, both inscribed tablets and impressed sealings. These impressions feature signs representing the names of Mesopotamian cities, many of them identifiable with known sites. The documents stand at the threshold of history, as the earliest evidence for inter-city engagement. Using an innovative methodology and interpretive framework of cultic resilience, we integrate archaeometric, iconographic, and functional analyses of the earliest stages of writing and sealing, to argue that the city seal evidence provides unique insights into inter-city cooperation by Mesopotamian cities during a critical episode of early urban development

Eukaryotic richness in the abyss: insights from pyrotag sequencing

Background: The deep sea floor is considered one of the most diverse ecosystems on Earth. Recent environmental DNA surveys based on clone libraries of rRNA genes confirm this observation and reveal a high diversity of eukaryotes present in deep-sea sediment samples. However, environmental clone-library surveys yield only a modest number of sequences with which to evaluate the diversity of abyssal eukaryotes. Methodology/Principal Findings: Here, we examined the richness of eukaryotic DNA in deep Arctic and Southern Ocean samples using massively parallel sequencing of the 18S ribosomal RNA (rRNA) V9 hypervariable region. In very small volumes of sediments, ranging from 0.35 to 0.7 g, we recovered up to 7,499 unique sequences per sample. By clustering sequences having up to 3 differences, we observed from 942 to 1756 Operational Taxonomic Units (OTUs) per sample. Taxonomic analyses of these OTUs showed that DNA of all major groups of eukaryotes is represented at the deep-sea floor. The dinoflagellates, cercozoans, ciliates, and euglenozoans predominate, contributing to 17%, 16%, 10%, and 8% of all assigned OTUs, respectively. Interestingly, many sequences represent photosynthetic taxa or are similar to those reported from the environmental surveys of surface waters. Moreover, each sample contained from 31 to 71 different metazoan OTUs despite the small sample volume collected. This indicates that a significant faction of the eukaryotic DNA sequences likely do not belong to living organisms, but represent either free, extracellular DNA or remains and resting stages of planktonic species. Conclusions/Significance: In view of our study, the deep-sea floor appears as a global DNA repository, which preserves genetic information about organisms living in the sediment, as well as in the water column above it. This information can be used for future monitoring of past and present environmental changes.French ANR Aquaparadox; ANR DeepOases; Swiss National Science Foundation [31003A-125372]; WM Keck foundationinfo:eu-repo/semantics/publishedVersio