TechSource (United States)

Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum, to facilitate delivery of active pharmaceutical ingredients to the underlying tissue. Numerous MAP products are proposed and there is significant clinical potential in priority areas such as vaccination. However, since their inception scientists have hypothesized about the risk of a clinically significant MAP-induced infection.Safety data from two major Phase 3 clinical trials involving hundreds of participants, who in total received tens of thousands of MAP applications, does not identify any clinically significant infections. However, the incumbent data set is not extensive enough to make definitive generalizable conclusions. A comprehensive assessment of the infection risk is therefore advised for MAP products, and this should be informed by clinical and pre-clinical data, theoretical analysis and informed opinions.In this article, a group of key stakeholders identify some of the key product- and patient-specific factors that may contribute to the risk of infection from a MAP product and provide expert opinions in the context of guidance from regulatory authorities. Considerations that are particularly pertinent to the MAP dosage form include the specifications of the finished product (e.g. microbial specification), it's design features, the setting for administration, the skill of the administrator, the anatomical application site, the target population and the clinical context. These factors, and others discussed in this article, provide a platform for the development of MAP risk assessments and a stimulus for early and open dialogue between developers, regulatory authorities and other key stakeholders, to expedite and promote development of safe and effective MAP products.

The higher efficiency of superconducting radio-frequency (SRF) cavities compared to normal-conducting ones enables the development of high-energy continuous-wave linear accelerators (linacs). Recent progress in the development of high-quality Nb$_3$Sn film coatings along with the availability of cryocoolers with high cooling capacity at 4 K makes it feasible to operate SRF cavities cooled by thermal conduction at relevant accelerating gradients for use in accelerators. A possible use of conduction-cooled SRF linacs is for environmental applications, requiring electron beams with energy of $1 - 10$ MeV and 1 MW of power. We have designed a 915 MHz SRF linac for such an application and developed a prototype single-cell cavity to prove the proposed design by operating it with cryocoolers at the accelerating gradient required for 1 MeV energy gain. The cavity has a $\sim 3$ $\mu$m thick Nb$_3$Sn film on the inner surface, deposited on a $\sim4$ mm thick bulk Nb substrate and a bulk $\sim7$ mm thick Cu outer shell with three Cu attachment tabs. The cavity was tested up to a peak surface magnetic field of 53 mT in liquid He at 4.3 K. A horizontal test cryostat was designed and built to test the cavity cooled with three Gifford-McMahon cryocoolers. The rf tests of the conduction-cooled cavity, performed at General Atomics, achieved a peak surface magnetic field of 50 mT and stable operation was possible with up to 18.5 W of rf heat load. The peak frequency shift due to microphonics was 23 Hz. These results represent the highest peak surface magnetic field achieved in a conduction-cooled SRF cavity to date and meet the requirements for a 1 MeV energy gain.

A new experiment collects data, since November 2019, at a depth of 210 m.w.e. in the Callio Lab in the Pyhasalmi mine in Finland. The setup, called NEMESIS (New Emma MEasurementS Including neutronS), incorporates infrastructure from the EMMA experiment with neutron and large-area plastic scintillator detectors. The experiment’s primary aim is to combine muon tracking with position-sensitive neutron detection to measure precision yields, multiplicities, and lateral distributions of high-multiplicity neutron events induced by cosmic muons in various materials. The data are relevant for background evaluation of the deep-underground searches for Dark Matter (DM), neutrino-less double beta decay, etc. Preliminary analysis revealed anomalies in muon-suppressed neutron multiplicity spectra collected during a 344-day run (live time) with a 565 kg Pb target. The spectra, otherwise well described by an exponential fit, show three peaks at high multiplicities. Although still at a low statistical significance, these small excesses match the outcome of an earlier measurement. The nature of the anomalies remains unclear, but, in principle, they may be a signature of self-annihilation of a WIMP with a mass close to 13 GeV/c2. With that assumption, the expected cross-section would be around 10−42 cm2 for Spin-Dependent or 10−46 cm2 for Spin Independent interactions. We propose verifying this hypothesis with an upgraded NEMESIS experiment, able to collect an order of magnitude more data than this measurement. Based on the statistical uncertainty, analysis of the event rate indicates that cross-section limits for DM mass range of approximately 3-40 GeV/c2 can be investigated with such a setup.

Abstract Technology development is typically the process of developing and demonstrating new or unproven technology, the application of existing technology to new or different uses, or the combination of existing and proven technology to achieve a specific goal. Technology development associated with a specific acquisition project for nuclear weapon typically should be identified early in the project life cycle and its maturity level should evolve to a confidence level that allows the project to establish a credible technical scope, schedule, and cost baseline. Projects that perform concurrent technology development and design implementation may run the risk of proceeding with an ill‐defined project baseline.In the climate of declining federal budgets and increased budget scrutiny, it is prudent to determine—as early as possible within a program schedule—the viability of technologies, and the ability of those technologies to support a specific project as well as the overall U.S. nuclear deterrent mission.This paper describes the approach and tools used within the nuclear weapons programs for assessing the maturity of technologies and their readiness for insertion into the project design and execution schedule.

A diagnostic to measure electron cloud formation and trapping in a quadrupole magnet has been developed, installed, and successfully tested at PSR. Beam studies with this diagnostic show that the electron flux striking the wall in the quadrupole is comparable to or larger than in an adjacent drift. In addition, the trapped electron signal, obtained using the sweeping feature of diagnostic, was larger than expected and decayed very slowly with an exponential time constant of 50 to 100 {micro}s. Experimental results were also obtained which suggest that a significant fraction of the electrons observed in the adjacent drift space were seeded by electrons ejected from the quadrupole.

The Fortran 90 RIAPMTQ/IMPACT code package is a pair of linked beam-dynamics simulation codes that have been developed for end-to-end computer simulations of multiple-charge state heavy-ion linacs for future exotic-beam facilities. The simulations can extend from the low-energy beam-transport line after the ECR ion source to the end of the linac. The work has been performed by a collaboration including LANL, LBNL, ANL, and MSU. The code RIAPMTQ simulates the linac front end including the LEBT, RFQ, and MEBT, and the code IMPACT simulates the main superconducting linac. The codes have been benchmarked for rms beam properties against previously existing codes at ANL and MSU. The codes allow high-statistics runs on parallel supercomputing platforms, such as NERSC at LBNL for studies of beam losses. The codes also run on desktop PC computers for low-statistics design work. We show results from 10-million-particle simulations at NERSC of designs by ANL and MSU for the Rare-Isotope Accelerator.

Theoretical fluxes of gamma rays escaping the surface of Mars were calculated. These and other calculated fluxes are needed to model the counting rates in the Mars Odyssey gamma ray spectrometer that are used to determine elemental compositions and other results using these measurements. Cross sections for the formation of gamma rays by both thermal and fast neutrons were compiled and evaluated. These evaluated cross sections were used with neutron fluxes calculated with the Monte Carlo N Particle Extended (MCNPX) code to get gamma ray production rates as a function of depth in the Martian surface. The fluxes of these gamma rays as a function of angle at the Martian surface were then calculated using gamma ray attenuation coefficients.

Abstract DPVL, a high‐level video stream protocol, facilitates the advancement of high information content monitors independently of whether displaying that information content is achieved within a single monitor unit or by an array of monitors. This proposed standard defines video packet structures, a capability management scheme and a monitor control scheme.