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[...]we conducted bi-variate correlations to determine whether degree of familiarity with individuals in recovery from SUDs at baseline was significantly associated with post-semester stigma scores. [...]students may have been affected by demand characteristics of the study (e.g., hypothesis guessing), training effects from the pre-test, or other procedural artifacts. [...]the addiction studies course was relatively brief (one semester) and not specifically designed to change stigma; instead, a reduction of stigma was expected to be a byproduct of having advanced education about addiction and exposure to the recovery community. [...]future research should focus on students enrolled in more comprehensive educational curricula on addiction that incorporates educational activities directly focused on changing stigmatizing attitudes.

Laser-driven particle accelerators have the potential to be much cheaper than conventional accelerators. But so far, the reliability and energy spread of the beams they produce has been poor. A technique that decouples the particle-injection and acceleration stages of these devices could improve their performance. Laser plasma accelerators 1 have produced high-quality electron beams with GeV energies from cm-scale devices 2 and are being investigated as hyperspectral fs light sources producing THz to γ -ray radiation 3 , 4 , 5 , and as drivers for future high-energy colliders 6 , 7 . These applications require a high degree of stability, beam quality and tunability. Here we report on a technique to inject electrons into the accelerating field of a laser-driven plasma wave and coupling of this injector to a lower-density, separately tunable plasma for further acceleration. The technique relies on a single laser pulse powering a plasma structure with a tailored longitudinal density profile, to produce beams that can be tuned in the range of 100– 400 MeV with per-cent-level stability, using laser pulses of less than 40 TW. The resulting device is a simple stand-alone accelerator or the front end for a multistage higher-energy accelerator.

Physics considerations for a next-generation linear collider based on laser-plasma accelerators are discussed. The ultrahigh accelerating gradient of a laser-plasma accelerator and short laser coupling distance between accelerator stages allows for a compact linac. Two regimes of laser-plasma acceleration are discussed. The highly nonlinear regime has the advantages of higher accelerating fields and uniform focusing forces, whereas the quasilinear regime has the advantage of symmetric accelerating properties for electrons and positrons. Scaling of various accelerator and collider parameters with respect to plasma density and laser wavelength are derived. Reduction of beamstrahlung effects implies the use of ultrashort bunches of moderate charge. The total linac length scales inversely with the square root of the plasma density, whereas the total power scales proportional to the square root of the density. A 1 TeV center-of-mass collider based on stages using a plasma density of 1017cm−3 requires tens of J of laser energy per stage (using 1μm wavelength lasers) with tens of kHz repetition rate. Coulomb scattering and synchrotron radiation are examined and found not to significantly degrade beam quality. A photon collider based on laser-plasma accelerated beams is also considered. The requirements for the scattering laser energy are comparable to those of a single laser-plasma accelerator stage.

Understanding dense matter hydrodynamics is critical for predicting plasma behavior in environments relevant to laser-driven inertial confinement fusion. Traditional diagnostic sources face limitations in brightness, spatiotemporal resolution, and in their ability to detect relevant electromagnetic fields. In this work, we present a dual-probe, multi-messenger laser wakefield accelerator platform combining ultrafast X-rays and relativistic electron beams at 1 Hz, to interrogate a free-flowing water target in vacuum, heated by an intense 200 ps laser pulse. This scheme enables high-repetition-rate tracking the evolution of the interaction using both particle types. Betatron X-rays reveal a cylindrically symmetric shock compression morphology assisted by low-density vapor, resembling foam-layer-assisted fusion targets. The synchronized electron beam detects time-evolving electromagnetic fields, uncovering charge separation and ion species differentiation during plasma expansion – phenomena not captured by photons or hydrodynamic simulations. We show that combining both probes provides complementary insights spanning kinetic to hydrodynamic regimes, highlighting the need for hybrid physics models to accurately predict fusion-relevant plasma behavior. The authors demonstrate dual-probe multi-messenger imaging of high-energy-density plasmas based on laser-wakefield-accelerated electrons. This enables spatiotemporally resolved simultaneous probing of plasma hydrodynamics and electromagnetic field evolution with both x-ray and electron beams.

Plasma accelerators sustain extreme field gradients and potentially enable future compact linear colliders. Although tremendous progress has been achieved in accelerating electron beams in a plasma accelerator, positron acceleration with collider-relevant parameters is challenging. A recently proposed positron acceleration scheme relying on the wake generated by an electron drive beam in a plasma column has been shown to be able to accelerate positron witness beams with low emittance and low energy spread. However, since this scheme relies on cylindrical symmetry, it is possibly prone to transverse instabilities that could lead, ultimately, to beam breakup. In this article, we show that the witness beam itself is subject to various damping mechanisms and, therefore, this positron acceleration scheme is inherently stable toward the misalignment of the drive and witness beams. This enables stable, high-quality plasma-based positron acceleration.

Late-stage cancer immunotherapy trials often lead to unusual survival curve shapes, like delayed curve separation or a plateauing curve in the treatment arm. It is critical for trial success to anticipate such effects in advance and adjust the design accordingly. Here, we use in silico cancer immunotherapy trials – simulated trials based on three different mathematical models – to assemble virtual patient cohorts undergoing late-stage immunotherapy, chemotherapy, or combination therapies. We find that all three simulation models predict the distinctive survival curve shapes commonly associated with immunotherapies. Considering four aspects of clinical trial design – sample size, endpoint, randomization rate, and interim analyses – we demonstrate how, by simulating various possible scenarios, the robustness of trial design choices can be scrutinized, and possible pitfalls can be identified in advance. We provide readily usable, web-based implementations of our three trial simulation models to facilitate their use by biomedical researchers, doctors, and trialists. Conventional clinical trial design methods are not necessarily tailored for the unique characteristics of immunotherapies. Here the authors use late-stage in silico cancer immunotherapy trials to investigate how design decisions affect the trial outcome.

The Agricultural Marketing Service (AMS) purchases beef for the National School Lunch Program and other federal nutrition assistance programs. For beef that will be delivered to food service facilities raw, each ca. 900-kg lot of boneless beef raw material and each ca. 4,500-kg sublot of resultant ground beef is tested for standard plate count (SPC) organisms, coliforms, and O157:H7. In addition, 1 of every 10 lots of boneless beef, randomly selected, is tested for O26, O45, O103, O111, O121, and O145. For beef that will be cooked using a validated lethality step at a federally inspected establishment before delivery, each lot of boneless beef and each sublot of ground beef is tested for SPC organisms, coliforms, and only. Any lot or sublot exceeding predefined critical limits (CLs) of 100,000 CFU g for SPC organisms, 1,000 CFU g for coliforms, or 500 CFU g for or for beef containing or any of previously mentioned serotypes is rejected for purchase. For school years 2015 through 2018 (July 2014 through June 2018), 220,497,254 kg of boneless beef and 189,347,318 kg of ground beef were produced for AMS. For boneless beef, 133 (0.06%), 164 (0.07%), and 106 (0.04%) of 240,488 lots exceeded CLs for SPC organisms, coliforms, and respectively; 2,038 (1.30%) and 116 (0.07%) of 156,671 lots were positive for and O157:H7, respectively; and 59 (0.36%) of 16,515 lots were positive for non-O157 Shiga toxin-producing . For ground beef, 46 (0.10%), 27 (0.06%), and 19 (0.04%) of 45,769 sublots exceeded CLs for SPC organisms, coliforms, and respectively; and 329 (1.40%) and 18 (0.08%) of 23,475 sublots were positive for and O157:H7, respectively. All lots and sublots found to exceed indicator organism CLs or to contain pathogens were identified, rejected for purchase, and diverted from federal nutrition assistance programs.

BackgroundResearch in migraine points towards central-peripheral complexity with a widespread pattern of structures involved. Migraine-associated neck and shoulder muscle pain has clinically been conceptualized as myofascial trigger points (mTrPs). However, concepts remain controversial, and the identification of mTrPs is mostly restricted to manual palpation in clinical routine. This study investigates a more objective, quantitative assessment of mTrPs by means of magnetic resonance imaging (MRI) with T2 mapping.MethodsTen subjects (nine females, 25.6 ± 5.2 years) with a diagnosis of migraine according to ICHD-3 underwent bilateral manual palpation of the upper trapezius muscles to localize mTrPs. Capsules were attached to the skin adjacent to the palpated mTrPs for marking. MRI of the neck and shoulder region was performed at 3 T, including a T2-prepared, three-dimensional (3D) turbo spin echo (TSE) sequence. The T2-prepared 3D TSE sequence was used to generate T2 maps, followed by manual placement of regions of interest (ROIs) covering the trapezius muscles of both sides and signal alterations attributable to mTrPs.ResultsThe trapezius muscles showed an average T2 value of 27.7 ± 1.4 ms for the right and an average T2 value of 28.7 ± 1.0 ms for the left side (p = 0.1055). Concerning signal alterations in T2 maps attributed to mTrPs, nine values were obtained for the right (32.3 ± 2.5 ms) and left side (33.0 ± 1.5 ms), respectively (p = 0.0781). When comparing the T2 values of the trapezius muscles to the T2 values extracted from the signal alterations attributed to the mTrPs of the ipsilateral side, we observed a statistically significant difference (p = 0.0039). T2 hyperintensities according to visual image inspection were only reported in four subjects for the right and in two subjects for the left side.ConclusionsOur approach enables the identification of mTrPs and their quantification in terms of T2 mapping even in the absence of qualitative signal alterations. Thus, it (1) might potentially challenge the current gold-standard method of physical examination of mTrPs, (2) could allow for more targeted and objectively verifiable interventions, and (3) could add valuable models to understand better central-peripheral mechanisms in migraine.

Defect engineering is foundational to classical electronic device development and for emerging quantum devices. Here, we report on defect engineering of silicon with ion pulses from a laser accelerator in the laser intensity range of 10 19  W cm −2 and ion flux levels of up to 10 22  ions cm −2 s −1 , about five orders of magnitude higher than conventional ion implanters. Low energy ions from plasma expansion of the laser-foil target are implanted near the surface and then diffuse into silicon samples locally pre-heated by high energy ions from the same laser-ion pulse. Silicon crystals exfoliate in the areas of highest energy deposition. Color centers, predominantly W and G-centers, form directly in response to ion pulses without a subsequent annealing step. We find that the linewidth of G-centers increases with high ion flux faster than the linewidth of W-centers, consistent with density functional theory calculations of their electronic structure. Intense ion pulses from a laser-accelerator drive materials far from equilibrium and enable direct local defect engineering and high flux doping of semiconductors. Defect engineering and doping of semiconductors by ion irradiation are essential in large-scale integration of electronic devices. Here, intense ion pulses from a laser-accelerator, with flux levels up to 10 22  ions cm -2 s -1 , are used to induce and optimize silicon color centers and photon emitters in the telecom band.

Invasive pulmonary aspergillosis is a major cause of death among immunosuppressed individuals despite the best available therapy. Depriving the pathogen of iron is an essential component of host defense in this infection, but the mechanisms by which the host achieves this are complex. Iron is essential to the virulence of Aspergillus species, and restricting iron availability is a critical mechanism of antimicrobial host defense. Macrophages recruited to the site of infection are at the crux of this process, employing multiple intersecting mechanisms to orchestrate iron sequestration from pathogens. To gain an integrated understanding of how this is achieved in aspergillosis, we generated a transcriptomic time series of the response of human monocyte-derived macrophages to Aspergillus and used this and the available literature to construct a mechanistic computational model of iron handling of macrophages during this infection. We found an overwhelming macrophage response beginning 2 to 4 h after exposure to the fungus, which included upregulated transcription of iron import proteins transferrin receptor-1, divalent metal transporter-1, and ZIP family transporters, and downregulated transcription of the iron exporter ferroportin. The computational model, based on a discrete dynamical systems framework, consisted of 21 3-state nodes, and was validated with additional experimental data that were not used in model generation. The model accurately captures the steady state and the trajectories of most of the quantitatively measured nodes. In the experimental data, we surprisingly found that transferrin receptor-1 upregulation preceded the induction of inflammatory cytokines, a feature that deviated from model predictions. Model simulations suggested that direct induction of transferrin receptor-1 (TfR1) after fungal recognition, independent of the iron regulatory protein-labile iron pool (IRP-LIP) system, explains this finding. We anticipate that this model will contribute to a quantitative understanding of iron regulation as a fundamental host defense mechanism during aspergillosis. IMPORTANCE Invasive pulmonary aspergillosis is a major cause of death among immunosuppressed individuals despite the best available therapy. Depriving the pathogen of iron is an essential component of host defense in this infection, but the mechanisms by which the host achieves this are complex. To understand how recruited macrophages mediate iron deprivation during the infection, we developed and validated a mechanistic computational model that integrates the available information in the field. The insights provided by this approach can help in designing iron modulation therapies as anti-fungal treatments.