The XENONnT dark matter experiment.

The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.9 tonnes of cryogenic liquid xenon (8.5 tonnes total mass in cryostat). The experiment is expected to extend the sensitivity to WIMP dark matter by more than an order of magnitude compared to XENON1T, thanks to the larger active mass and the significantly reduced background, improved by novel systems such as a radon removal plant and a neutron veto. This article describes the XENONnT experiment and its sub-systems in detail and reports on the detector performance during the first science run.

Prevention of venous thromboembolic events in patients with lower leg immobilization after trauma: Systematic review and network meta-analysis with meta-epsidemiological approach.

BACKGROUND: Lower limb trauma requiring immobilization is a significant contributor to overall venous thromboembolism (VTE) burden. The clinical effectiveness of thromboprophylaxis for this indication and the optimal agent strategy are still a matter of debate. Our main objective was to assess the efficacy of pharmacological thromboprophylaxis to prevent VTE in patients with isolated temporary lower limb immobilization after trauma. We aimed to estimate and compare the clinical efficacy and the safety of the different thromboprophylactic treatments to determine the best strategy. METHODS AND FINDINGS: We conducted a systematic review and a Bayesian network meta-analysis (NMA) including all available randomized trials comparing a pharmacological thromboprophylactic treatment to placebo or to no treatment in patients with leg immobilization after trauma. We searched Medline, Embase, and Web of Science until July 2021. Only RCT or observational studies with analysis of confounding factors including adult patients requiring temporary immobilization for an isolated lower limb injury treated conservatively or surgically and assessing pharmacological thromboprophylactic agents or placebo or no treatment were eligible for inclusion. The primary endpoint was the incidence of major VTE (proximal deep vein thrombosis, symptomatic VTE, and pulmonary embolism-related death). We extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses for NMA and appraised selected trials with the Cochrane review handbook. Fourteen studies were included (8,198 patients). Compared to the control group, rivaroxaban, fondaparinux, and low molecular weight heparins were associated with a significant risk reduction of major VTE with an odds ratio of 0.02 (95% credible interval (CrI) 0.00 to 0.19), 0.22 (95% CrI 0.06 to 0.65), and 0.32 (95% CrI 0.15 to 0.56), respectively. No increase of the major bleeding risk was observed with either treatment. Rivaroxaban has the highest likelihood of being ranked top in terms of efficacy and net clinical benefit. The main limitation is that the network had as many indirect comparisons as direct comparisons. CONCLUSIONS: This NMA confirms the favorable benefit/risk ratio of thromboprophylaxis for patients with leg immobilization after trauma with the highest level of evidence for rivaroxaban. TRIAL REGISTRATION: PROSPERO CRD42021257669.

Assessment of physicians' resilience level during the COVID-19 pandemic.

We aim to assess physicians' level of resilience and define factors that improve or decrease the resilience level during the COVID-19 pandemic. Physicians from hospitals located in areas with different COVID-19 caseload levels, were invited to participate in a national e-survey between April and May 2020. Study participants were mainly emergency physicians, and anaesthesiologists, infectious disease consultants, and intensive care. The survey assessed participant's characteristics, factors potentially associated with resilience, and resilience using the Connor-Davidson Resilience Scale (RISC-25), with higher scores indicative of greater resilience. Factors associated with the resilience score were assessed using a multivariable linear regression. Of 451 responding physicians involved in the care of COVID-19 patients, 442 were included (98%). Age was 36.1 ± 10.3 years and 51.8% were male; 63% worked in the emergency department (n = 282), 10.4% in anesthesiology (n = 46), 9.9% in infectious disease department (n = 44), 4.8% in intensive care unit (n = 21) or other specialties (n = 49). The median RISC-25 score was at 69 (IQR 62-75). Factors associated with higher RISC scores were anesthesia as a specialty, parenthood, no previous history of anxiety or depression and nor increased anxiety. To conclude, this study is the first to characterize levels of resilience among physicians involved in COVID-19 unit. Our data points to certain protective characteristics and some detrimental factors, such as anxiety or depression, that could be amenable to remediating or preventing strategies to promote resilience and support caregivers in a pandemic.

Venous thromboembolism risk stratification for patients with lower limb trauma and cast or brace immobilization.

BACKGROUND: Thromboprophylaxis for patients with non-surgical isolated lower-limb trauma requiring immobilization is a matter of debate. Our aim was to develop and validate a clinical risk- stratification model based on Trauma, Immobilization and Patients' characteristics (the TIP score). METHODS: The TIP score criteria and the cut-off were selected by a consensus of international experts (n = 27) using the Delphi method. Retrospective validation was performed in a population-based case-control study (MEGA study). The potential score's impact in anticoagulant treatment was assessed in a prospective single-center observational cohort study. FINDINGS: After four successive rounds, 30 items constituting the TIP score were selected: thirteen items for trauma, three for immobilization and 14 for patient characteristics were selected, each rated on a scale of 1 to 3. In the validation database, the TIP score had an AUC of 0·77 (95% CI 0.70 to 0.85). Using the cut-off proposed by the experts (≥5) and assuming a prevalence of 1·8%, the TIP scores had a sensitivity, specificity and negative predictive values of 89·9%, 30·7% and 99·4% respectively. In the prospective cohort, 84·2% (165/196) of all the patients concerned who presented at the emergency department had a low VTE risk not requiring thromboprophylaxis according to their TIP scores. The 3-month rate of symptomatic VTE was 1/196 [95% CI 0.1-2.8] this patient was in the sub-group TIP score ≥5. CONCLUSION: For patients with non-surgical lower-limb trauma and orthopedic immobilization, the TIP score allows an individual VTE risk-assessment and shows promising results in guiding thromboprophylaxis.

High repetition rate plasma mirror device for attosecond science.

This report describes an active solid target positioning device for driving plasma mirrors with high repetition rate ultra-high intensity lasers. The position of the solid target surface with respect to the laser focus is optically monitored and mechanically controlled on the nm scale to ensure reproducible interaction conditions for each shot at arbitrary repetition rate. We demonstrate the target capabilities by driving high-order harmonic generation from plasma mirrors produced on glass targets with a near-relativistic intensity few-cycle pulse laser system operating at 1 kHz. During experiments, residual target surface motion can be actively stabilized down to 47 nm (root mean square), which ensures sub-300-as relative temporal stability of the plasma mirror as a secondary source of coherent attosecond extreme ultraviolet radiation in pump-probe experiments.

Observation of longitudinal and transverse self-injections in laser-plasma accelerators.

Laser-plasma accelerators can produce high-quality electron beams, up to giga electronvolts in energy, from a centimetre scale device. The properties of the electron beams and the accelerator stability are largely determined by the injection stage of electrons into the accelerator. The simplest mechanism of injection is self-injection, in which the wakefield is strong enough to trap cold plasma electrons into the laser wake. The main drawback of this method is its lack of shot-to-shot stability. Here we present experimental and numerical results that demonstrate the existence of two different self-injection mechanisms. Transverse self-injection is shown to lead to low stability and poor-quality electron beams, because of a strong dependence on the intensity profile of the laser pulse. In contrast, longitudinal injection, which is unambiguously observed for the first time, is shown to lead to much more stable acceleration and higher-quality electron beams.

Aberration-free laser beam in the soft x-ray range.

By seeding an optical-field-ionized population-inverted plasma amplifier with the 25th harmonic of an IR laser, we have achieved what we believe to be the first aberration-free laser beam in the soft x-ray spectral range. This laser emits within a cone of 1.34 mrad(1/e(2)) at a repetition rate of 10 Hz at a central wavelength of 32.8 nm. The beam exhibits a circular profile and wavefront distortions as low as lambda/17. A theoretical analysis of these results shows that this high beam quality is due to spatial filtering of the seed beam by the plasma amplifier aperture.

A high-intensity highly coherent soft X-ray femtosecond laser seeded by a high harmonic beam.

Synchrotrons have for decades provided invaluable sources of soft X-rays, the application of which has led to significant progress in many areas of science and technology. But future applications of soft X-rays--in structural biology, for example--anticipate the need for pulses with much shorter duration (femtoseconds) and much higher energy (millijoules) than those delivered by synchrotrons. Soft X-ray free-electron lasers should fulfil these requirements but will be limited in number; the pressure on beamtime is therefore likely to be considerable. Laser-driven soft X-ray sources offer a comparatively inexpensive and widely available alternative, but have encountered practical bottlenecks in the quest for high intensities. Here we establish and characterize a soft X-ray laser chain that shows how these bottlenecks can in principle be overcome. By combining the high optical quality available from high-harmonic laser sources (as a seed beam) with a highly energetic soft X-ray laser plasma amplifier, we produce a tabletop soft X-ray femtosecond laser operating at 10 Hz and exhibiting full saturation, high energy, high coherence and full polarization. This technique should be readily applicable on all existing laser-driven soft X-ray facilities.

Imaging and quality assessment of high-harmonic focal spots.

We present a direct method of studying the focusability of an intense, short-pulse extreme-ultraviolet (XUV) beam obtained by high-harmonic generation. We perform near-field imaging of the focal spot of five high-harmonic orders strongly focused by a broadband toroidal mirror. To visualize the focal spot directly, we image the fluorescence induced by an XUV beam on a cerium-doped YAG crystal on a visible CCD camera. We can thus measure the harmonic spot size on a single image, together with the Strehl ratio, to evaluate the quality of focusing. Such techniques should become instrumental in optimizing the focusing conditions and reaching intensities required for exploring attosecond nonlinear optics in the XUV range.

Global optimization of high harmonic generation.

We investigate the relevance of the absorption limit concept in the optimization of high harmonic generation. Thanks to the first direct observation of the coherence length of the process from high-contrast Maker fringes, we unravel experimental conditions for which the harmonic dipole response is enhanced when phase matching is realized within the absorption limit, leading to record conversion efficiencies in argon. Moreover, we show that harmonic generation in guided or freely propagating geometries are equivalent in the loose focusing regime. This analysis is generalized to other advanced phase-matching schemes, thereby predicting the possibility to boost the conversion efficiencies using light noble gases.