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OBJECTIVES:The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs. DESIGN:We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses. SETTING:Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. PATIENTS:Adult patients presenting to the emergency department with severe sepsis or septic shock. INTERVENTIONS:EGDT vs. usual care. MEASUREMENTS AND MAIN RESULTS:A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p< 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], –8% [–19% to 4%] and relative risk reduction, 1.34 [0.89–2.01] in quintile 1 suggesting harm from EGDT, and 12% [1–23%] and 0.64 [0.42–0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive. CONCLUSIONS:Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE. 

A compact high-flux, short-pulse neutron source would have applications from nuclear astrophysics to cancer therapy. Laser-driven neutron sources can achieve fluxes much higher than spallation and reactor neutron sources by reducing the volume and time in which the neutron-producing reactions occur by orders of magnitude. We report progress towards an efficient laser-driven neutron source in experiments with a cryogenic deuterium jet on the Texas Petawatt laser. Neutrons were produced both by laser-accelerated multi-MeV deuterons colliding with Be and mixed metallic catchers and by d ( d , n ) 3 He fusion reactions within the jet. We observed deuteron yields of 10 13 /shot in quasi-Maxwellian distributions carrying ∼ 8 − 10 % of the input laser energy. We obtained neutron yields greater than 10 10 /shot and found indications of a deuteron-deuteron fusion neutron source with high peak flux ( > 1 0 22 cm −2  s −1 ). The estimated fusion neutron yield in our experiment is one order of magnitude higher than any previous laser-induced dd fusion reaction. Though many technical challenges will have to be overcome to convert this proof-of-principle experiment into a consistent ultra-high flux neutron source, the neutron fluxes achieved here suggest laser-driven neutron sources can support laboratory study of the rapid neutron-capture process, which is otherwise thought to occur only in astrophysical sites such as core-collapse supernova, and binary neutron star mergers. 

We present the first measurement of cosmic-ray fluxes of ${}^6\mathrm{Li}$and ${}^7\mathrm{Li}$isotopes in the rigidity range from 1.9 to 25 GV. The measurements are based on $9.7\times {10}^5$ ${}^6\mathrm{Li}$and $1.04\times {10}^6$ ${}^7\mathrm{Li}$nuclei collected by the Alpha Magnetic Spectrometer on the International Space Station from May 2011 to October 2023. We observe that over the entire rigidity range the ${}^6\mathrm{Li}$and ${}^7\mathrm{Li}$fluxes exhibit nearly identical time variations and, above $\sim 4\mathrm{GV}$, the time variations of ${}^6\mathrm{Li}$, ${}^7\mathrm{Li}$, He, Be, B, C, N, and O fluxes are identical. Above $\sim 7\mathrm{GV}$, we find an identical rigidity dependence of the ${}^6\mathrm{Li}$and ${}^7\mathrm{Li}$fluxes. This shows that they are both produced by collisions of heavier cosmic-ray nuclei with the interstellar medium and, in particular, excludes the existence of a sizable primary component in the ${}^7\mathrm{Li}$flux. Published by the American Physical Society2025 

We report the properties of precision time structures of cosmic nuclei He, Li, Be, B, C, N, and O fluxes over an 11-year solar cycle from May 2011 to November 2022 in the rigidity range from 1.92 to 60.3 GV. The nuclei fluxes show similar but not identical time variations with amplitudes decreasing with increasing rigidity. In particular, below 3.64 GV the Li, Be, and B fluxes, and below 2.15 GV the C, N, and O fluxes, are significantly less affected by solar modulation than the He flux. We observe that these differences in solar modulation are linearly correlated with the differences in the spectral indices of the cosmic nuclei fluxes. This shows, in a model-independent way, that solar modulation of galactic cosmic nuclei depends on their spectral shape. In addition, solar modulation differences due to nuclei velocity dependence on the mass-to-charge ratio ( $A/Z$) are not observed. Published by the American Physical Society2025 

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron ( $D$) flux are presented. The measurements are based on $21\times {10}^6$ $D$nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the $D$flux exhibits nearly identical time variations with the $p$, ${}^3\mathrm{He}$, and ${}^4\mathrm{He}$fluxes. Above 4.5 GV, the $D/{}^4\mathrm{He}$flux ratio is time independent and its rigidity dependence is well described by a single power law $\propto R^{\mathrm{\Delta }}$with ${\mathrm{\Delta }}_{D/{}^4\mathrm{He}}=-0.108\pm 0.005$. This is in contrast with the ${}^3\mathrm{He}/{}^4\mathrm{He}$flux ratio for which we find ${\mathrm{\Delta }}_{{}^3\mathrm{He}/{}^4\mathrm{He}}=-0.289\pm 0.003$. Above $\sim 13\mathrm{GV}$we find a nearly identical rigidity dependence of the $D$and $p$fluxes with a $D/p$flux ratio of $0.027\pm 0.001$. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the $D$flux equal to $9.4\pm 0.5\%$of the ${}^4\mathrm{He}$flux and the secondary component of the $D$flux equal to $58\pm 5\%$of the ${}^3\mathrm{He}$flux. Published by the American Physical Society2024