Higgs Oscillations in a Unitary Fermi Superfluid.

Symmetry-breaking phase transitions are central to our understanding of states of matter. When a continuous symmetry is spontaneously broken, new excitations appear that are tied to fluctuations of the order parameter. In superconductors and fermionic superfluids, the phase and amplitude can fluctuate independently, giving rise to two distinct collective branches. However, amplitude fluctuations are difficult to both generate and measure, as they do not couple directly to the density of fermions and have only been observed indirectly to date. Here, we excite amplitude oscillations in an atomic Fermi gas with resonant interactions by an interaction quench. Exploiting the sensitivity of Bragg spectroscopy to the amplitude of the order parameter, we measure the time-resolved response of the atom cloud, directly revealing amplitude oscillations at twice the frequency of the gap. The magnitude of the oscillatory response shows a strong temperature dependence, and the oscillations appear to decay faster than predicted by time-dependent Bardeen-Cooper-Schrieffer theory applied to our experimental setup.

Emergent Inflation of the Efimov Spectrum under Three-Body Spin-Exchange Interactions.

We resolve the unexpected and long-standing disagreement between experiment and theory in the Efimovian three-body spectrum of ^{7}Li, commonly referred to as the lithium few-body puzzle. Our results show that the discrepancy arises out of the presence of strong nonuniversal three-body spin-exchange interactions, which enact an effective inflation of the universal Efimov spectrum. This conclusion is obtained from a thorough numerical solution of the quantum mechanical three-body problem, including precise interatomic interactions and all spin degrees of freedom for three alkali-metal atoms. Our results show excellent agreement with the experimental data regarding both the Efimov spectrum and the absolute rate constants of three-body recombination, and in addition reveal a general product propensity for such triatomic reactions in the Paschen-Back regime, stemming from Wigner's spin conservation rule.

Time Trends in Causes of Death in People with HIV: Insights from the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in acquired immunodeficiency syndrome (AIDS)-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years is scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005-2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female at birth. Out of these deaths, 147 (9.0%) were HIV/AIDS-related, 373 (22.9%) due to non-AIDS, non-hepatic (NANH) cancers, 166 (10.2%) liver-related, and 158 (9.7%) cardiovascular-related. The median age at death increased from 45.0 [40.0,53.0] years in 2005-2007 to 61.0 [56.0,69.5] years in 2020-2022. HIV/AIDS and liver-related causes of death decreased, whereas deaths from NANH cancers increased, and cardiovascular-related deaths remained relatively stable. CONCLUSION: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus co-infection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbidities, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

Time-resolved X-ray diffraction diagnostic development for the National Ignition Facility.

We present the development of an experimental platform that can collect four frames of x-ray diffraction data along a single line of sight during laser-driven, dynamic-compression experiments at the National Ignition Facility. The platform is comprised of a diagnostic imager built around ultrafast sensors with a 2-ns integration time, a custom target assembly that serves also to shield the imager, and a 10-ns duration, quasi-monochromatic x-ray source produced by laser-generated plasma. We demonstrate the performance with diffraction data for Pb ramp compressed to 150 GPa and illuminated by a Ge x-ray source that produces ∼7 × 1011, 10.25-keV photons/ns at the 400 µm diameter sample.

Extended X-ray absorption fine structure of dynamically-compressed copper up to 1 terapascal.

Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal. These results nearly double the highest pressure at which extended x-ray absorption fine structure has been reported in any material. In this work, the copper temperature is unexpectedly found to be much higher than predicted when adjacent to diamond layer(s), demonstrating the important influence of the sample environment on the thermal state of materials; this effect may introduce additional temperature uncertainties in some previous experiments using diamond and provides new guidance for future experimental design.

Thermodynamic fluctuation theorems govern human sensorimotor learning.

The application of thermodynamic reasoning in the study of learning systems has a long tradition. Recently, new tools relating perfect thermodynamic adaptation to the adaptation process have been developed. These results, known as fluctuation theorems, have been tested experimentally in several physical scenarios and, moreover, they have been shown to be valid under broad mathematical conditions. Hence, although not experimentally challenged yet, they are presumed to apply to learning systems as well. Here we address this challenge by testing the applicability of fluctuation theorems in learning systems, more specifically, in human sensorimotor learning. In particular, we relate adaptive movement trajectories in a changing visuomotor rotation task to fully adapted steady-state behavior of individual participants. We find that human adaptive behavior in our task is generally consistent with fluctuation theorem predictions and discuss the merits and limitations of the approach.

Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution: Implementation of Causal Inference Methods.

This report provides a final summary of the principal findings and key conclusions of a study supported by an HEI grant aimed at "Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution." It is the second and final report on this topic. The study was designed to advance four critical areas of inquiry and methods development. First, it focused on predicting short- and long-term exposures to ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) at high spatial resolution (1 km × 1 km) for the continental United States over the period 2000-2016 and linking these predictions to health data. Second, it developed new causal inference methods for estimating exposure-response (ER) curves (ERCs) and adjusting for measured confounders. Third, it applied these methods to claims data from Medicare and Medicaid beneficiaries to estimate health effects associated with short- and long-term exposure to low levels of ambient air pollution. Finally, it developed pipelines for reproducible research, including approaches for data sharing, record linkage, and statistical software. Our HEI-funded work has supported an extensive portfolio of analyses and the development of statistical methods that can be used to robustly understand the health effects of short- and long-term exposure to low levels of ambient air pollution. Our Phase 1 report (Dominici et al. 2019) provided a high-level overview of our statistical methods, data analysis, and key findings, grouped into the following five areas: (1) exposure prediction, (2) epidemiological studies of ambient exposures to air pollution at low levels, (3) sensitivity analysis, (4) methodological contributions in causal inference, and (5) an open access research data platform. The current, final report includes a comprehensive overview of the entire research project.Considering our (1) massive study population, (2) numerous sensitivity analyses, and (3) transparent assessment of covariate balance indicating the quality of causal inference for simulating randomized experiments, we conclude that conditionally on the required assumptions for causal inference, our results collectively indicate that long-term PM2.5 exposure is likely to be causally related to mortality. This conclusion assumes that the causal inference assumptions hold and, more specifically, that we accounted adequately for confounding bias. We explored various modeling approaches, conducted extensive sensitivity analyses, and found that our results were robust across approaches and models. This work relied on publicly available data, and we have provided code that allows for reproducibility of our analyses.Our work provides comprehensive evidence of associations between exposures to PM2.5, NO2, and O3 and various health outcomes. In the current report, we report more specific results on the causal link between long-term exposure to PM2.5 and mortality, even at PM2.5 levels below or equal to 12 µg/m3, and mortality among Medicare beneficiaries (ages 65 and older). This work relies on newly developed causal inference methods for continuous exposure.For the period 2000-2016, we found that all statistical approaches led to consistent results: a 10-µg/m3 decrease in PM2.5 led to a statistically significant decrease in mortality rate ranging between 6% and 7% (= 1 - 1/hazard ratio [HR]) (HR estimates 1.06 [95% CI, 1.05 to 1.08] to 1.08 [95% CI, 1.07 to 1.09]). The estimated HRs were larger when studying the cohort of Medicare beneficiaries that were always exposed to PM2.5 levels lower than 12 µg/m3 (1.23 [95% CI, 1.18 to 1.28] to 1.37 [95% CI, 1.34 to 1.40]).Comparing the results from multiple and single pollutant models, we found that adjusting for the other two pollutants slightly attenuated the causal effects of PM2.5 and slightly elevated the causal effects of NO2 exposure on all-cause mortality. The results for O3 remained almost unchanged.We found evidence of a harmful causal relationship between mortality and long-term PM2.5 exposures adjusted for NO2 and O3 across the range of annual averages between 2.77 and 17.16 µg/m3 (included >98% of observations) in the entire cohort of Medicare beneficiaries across the continental United States from 2000 to 2016. Our results are consistent with recent epidemiological studies reporting a strong association between long-term exposure to PM2.5 and adverse health outcomes at low exposure levels. Importantly, the curve was almost linear at exposure levels lower than the current national standards, indicating aggravated harmful effects at exposure levels even below these standards.There is, in general, a harmful causal impact of long-term NO2 exposures to mortality adjusted for PM2.5 and O3 across the range of annual averages between 3.4 and 80 ppb (included >98% of observations). Yet within low levels (annual mean ≤53 ppb) below the current national standards, the causal impacts of NO2 exposures on all-cause mortality are nonlinear with statistical uncertainty.The ERCs of long-term O3 exposures on all-cause mortality adjusted for PM2.5 and NO2 are almost flat below 45 ppb, which shows no statistically significant effect. Yet we observed an increased hazard when the O3 exposures were higher than 45 ppb, and the HR was approximately 1.10 when comparing Medicare beneficiaries with annual mean O3 exposures of 50 ppb versus those with 30 ppb.institutions, including those that support the Health Effects Institute; therefore, it may not reflect the views or policies of these parties, and no endorsement by them should be inferred.A list of abbreviations and other terms appears at the end of this volume.

Cortisol awakening response in the airborne rescue service.

BACKGROUND: Work-related stress may lead to mental and physical illnesses. Emergency physicians may be particularly vulnerable to developing such diseases due to their extreme emotional working environment. AIMS: The purpose of the study was to analyse the hormonal stress burden of emergency physicians in the airborne rescue service to create an empirical basis for developing appropriate measures against chronic stress in the rescue service. METHODS: Three salivary cortisol samples were collected after awakening in 15 min intervals-each on a flight rescue day, a clinic day and a free day-to calculate the extent of the hormonal stress load of the emergency physicians. A nested linear mixed-model analysis was used in 40 cases to investigate hormonal stress. Furthermore, professional years and gender were included in the calculations. RESULTS: The mixed model showed neither a main effect for measurement time nor for day but a significant interaction effect (P = 0.002). The cortisol level rises strongly on the flight rescue and the clinic day, while on the free day it shows a moderate increase. Professional years and gender also proved to be statistically significant for the cortisol level of emergency physicians (P < 0.001). CONCLUSIONS: The results show a significantly higher cortisol increase on working days compared with a free day, which indicates a stronger stress burden on working days of emergency physicians in the airborne rescue service. Future studies should examine the stress level of emergency physicians in more detail to prove whether the working conditions of emergency physicians need to be modified.

Participation, retention and uptake in a multicentre pre-exposure prophylaxis cohort using online, smartphone-compatible data collection.

OBJECTIVES: The aim of the study was to assess the feasibility of a national pre-exposure prophylaxis (PrEP) programme using smartphone-compatible data collection. METHODS: This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone-compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV-negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow-up (number with first follow-up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. RESULTS: Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52-137]. Retention at first follow-up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33-47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. CONCLUSIONS: In a national PrEP programme using smartphone-compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.

[Tourniquet use in the Helicopter Emergency Medical Service : Analysis based on data of the DRF Luftrettung (German Air Rescue) in the period 2015-2020]. / Der Einsatz von Tourniquets im Rahmen der Luftrettung : Analyse anhand der Daten der DRF Luftrettung im Zeitraum 2015­2020.

BACKGROUND: In 2016 the first German recommendation for the preclinical use of tourniquets was published. Currently little is known of the frequency of the use of tourniquets in the prehospital setting in Germany. This study evaluated how often a tourniquet is used in a civilian German Helicopter Emergency Medical Service (HEMS). METHOD: After the approval of the scientific working group of the DRF Luftrettung HEMS, the electronic database (HEMSDER) of the DRF Luftrettung HEMS was analyzed for the period 2015-2020 under the abovementioned question. All patients with a tourniquet application were included in the study and a comparison was made with the total trauma cohort and a subgroup analysis between patients who additionally required airway management and patients without additional airway management in the cohort of tourniquet patients. The analysis was mainly descriptive. Parametric test (t-tests and χ2-tests) were used for group comparison. RESULTS: During the study period 67,321 trauma patients were treated and in 866 (1.3% of all trauma patients) a tourniquet was used. The mean age of these patients was 45.9 years (±19.5 years), 710 (84%) were male, 439 (51%) suffered a monotrauma, 296 (34%) suffered multiple trauma, 339 (38%) required a prehospital airway management and 321 (37%) of these were intubated. Significant differences between patients with tourniquet application and the rest of the trauma cohort were detected in general data (monotrauma, polytrauma and high-speed trauma, massive bleeding), vital signs at the scene of the accident (GCS, HF, SpO2) and necessary interventions, such as pressure bandages and use of hemostyptics, tranexamic acid, analgesia, the frequency of intubation and colloidal volume replacement. Due to limitations of the data set we could not obtain information regarding the limb used for the tourniquet, whether a conversion of the tourniquet was carried out and if the tourniquet was used according to the current German trauma guidelines. CONCLUSION: With a frequency of 1.3% the need for a prehospital tourniquet application is low in civilian trauma patients. Monotrauma with isolated extremity injuries represent about half of the patients treated with tourniquets. The other half is represented by multiple injuries or multiple trauma patients who require significantly more invasive measures, such as airway management and more complex on-scene interventions are needed. The available data do not allow any conclusions to be drawn about the location and the quality of the tourniquet application. Future documentation systems should incorporate data on the use of tourniquets, such as the location of use, indications (tactical use/massive bleeding), bleeding control achieved (yes/no) or second tourniquet necessary, conversion (yes/no) and any obvious complications.

Untargeted and targeted analysis of sarin poisoning biomarkers in rat urine by liquid chromatography and tandem mass spectrometry.

Chemical warfare agents continue to pose a real threat to humanity, despite their prohibition under the Chemical Weapons Convention. Sarin is one of the most toxic and lethal representatives of nerve agents. The methodology for the targeted analysis of known sarin metabolites has reached great heights, but little attention has been paid to the untargeted analysis of biological samples of victims exposed to this deadly poisonous substance. At present, the development of computational and statistical methods of analysis offers great opportunities for finding new metabolites or understanding the mechanisms of action or effect of toxic substances on the organism. This study presents the targeted LC-MS/MS determination of methylphosphonic acid and isopropyl methylphosphonic acid in the urine of rats exposed to a non-lethal dose of sarin, as well as the untarget urine analysis by LC-HRMS. Targeted analysis of polar acidic sarin metabolites was performed on a mixed-mode reversed-phase anion-exchange column, and untargeted analysis on a conventional reversed-phase C18 column. Isopropyl methylphosphonic acid was detected and quantified within 5 days after subcutaneous injection of sarin at a dose of 1/4 LD50. A combination of generalized additive mixed models and dose-response analysis with database searches using accurate mass of precursor ions and corresponding MS/MS spectra enabled us to propose new six potential biomarkers of biological response to exposure. The results confirm the well-known fact that sarin poisoning has a significant impact on the victims' metabolome, with inhibition of acetylcholinesterase being just the first step and trigger of the complex toxicodynamic response.

Heat flows in rock cracks naturally optimize salt compositions for ribozymes.

Catalytic nucleic acids, such as ribozymes, are central to a variety of origin-of-life scenarios. Typically, they require elevated magnesium concentrations for folding and activity, but their function can be inhibited by high concentrations of monovalent salts. Here we show that geologically plausible high-sodium, low-magnesium solutions derived from leaching basalt (rock and remelted glass) inhibit ribozyme catalysis, but that this activity can be rescued by selective magnesium up-concentration by heat flow across rock fissures. In contrast to up-concentration by dehydration or freezing, this system is so far from equilibrium that it can actively alter the Mg:Na salt ratio to an extent that enables key ribozyme activities, such as self-replication and RNA extension, in otherwise challenging solution conditions. The principle demonstrated here is applicable to a broad range of salt concentrations and compositions, and, as such, highly relevant to various origin-of-life scenarios.

Establishing gold and platinum standards to 1 terapascal using shockless compression.

New techniques are advancing the frontier of high-pressure physics beyond 1 terapascal, leading to new discoveries and offering stringent tests for condensed-matter theory and advanced numerical methods. However, the ability to absolutely determine the pressure state remains challenging, and well-calibrated pressure-density reference materials are required. We conducted shockless dynamic compression experiments at the National Ignition Facility and the Z machine to obtain quasi-absolute, high-precision, pressure-density equation-of-state data for gold and platinum. We derived two experimentally constrained pressure standards to terapascal conditions. Establishing accurate experimental determinations of extreme pressure will facilitate better connections between experiments and theory, paving the way toward improving our understanding of material response to these extreme conditions.

Probing the Solar Meridional Circulation Using Fourier Legendre Decomposition.

We apply the helioseismic methodology of Fourier Legendre decomposition to 88 months of Dopplergrams obtained by the Helioseismic and Magnetic Imager (HMI) as the basis of inferring the depth variation of the mean meridional flow, as averaged between 20° and 60° latitude and in time, in both the northern and southern hemispheres. We develop and apply control procedures designed to assess and remove center-to-limb artifacts using measurements obtained by performing the analysis with respect to artificial poles at the east and west limbs. Forward modeling is carried out using sensitivity functions proportional to the mode kinetic energy density to evaluate the consistency of the corrected frequency shifts with models of the depth variation of the meridional circulation in the top half of the convection zone. The results, taken at face value, imply substantial differences between the meridional circulation in the northern and southern hemispheres. The inferred presence of a return (equatorward propagating) flow at a depth of approximately 40 Mm below the photosphere in the northern hemisphere is surprising and appears to be inconsistent with many other helioseismic analyses. This discrepancy may be the result of the inadequacy of our methodology to remove systematic errors in HMI data. Our results appear to be at least qualitatively similar to those by Gizon et al., which point to an anomaly in HMI data that is not present in MDI or GONG data.

Metastability of diamond ramp-compressed to 2 terapascals.

Carbon is the fourth-most prevalent element in the Universe and essential for all known life. In the elemental form it is found in multiple allotropes, including graphite, diamond and fullerenes, and it has long been predicted that even more structures can exist at pressures greater than those at Earth's core1-3. Several phases have been predicted to exist in the multi-terapascal regime, which is important for accurate modelling of the interiors of carbon-rich exoplanets4,5. By compressing solid carbon to 2 terapascals (20 million atmospheres; more than five times the pressure at Earth's core) using ramp-shaped laser pulses and simultaneously measuring nanosecond-duration time-resolved X-ray diffraction, we found that solid carbon retains the diamond structure far beyond its regime of predicted stability. The results confirm predictions that the strength of the tetrahedral molecular orbital bonds in diamond persists under enormous pressure, resulting in large energy barriers that hinder conversion to more-stable high-pressure allotropes1,2, just as graphite formation from metastable diamond is kinetically hindered at atmospheric pressure. This work nearly doubles the highest pressure at which X-ray diffraction has been recorded on any material.

Role of soluble guanylyl cyclase in renal afferent and efferent arterioles.

Renal arteriolar tone depends considerably on the dilatory action of nitric oxide (NO) via activation of soluble guanylyl cyclase (sGC) and cGMP action. NO deficiency and hypoxia/reoxygenation are important pathophysiological factors in the development of acute kidney injury. It was hypothesized that the NO-sGC-cGMP system functions differently in renal afferent arterioles (AA) compared with efferent arterioles (EA) and that the sGC activator cinaciguat differentially dilates these arterioles. Experiments were performed in isolated, perfused mouse glomerular arterioles. Hypoxia (0.1% oxygen) was achieved by using a hypoxia chamber. Phosphodiesterase 5 (PDE5) and sGC subunits were considerably expressed on the mRNA level in AA. PDE5 inhibition with sildenafil, which blocks cGMP degradation, diminished the responses to ANG II bolus application in AA, but not significantly in EA. Vasodilation induced by sildenafil in ANG II-preconstricted vessels was stronger in EA than AA. Cinaciguat, an NO- and heme-independent sGC activator, dilated EA more strongly than AA after NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) treatment and preconstriction with ANG II. Cinaciguat-induced dilatation of l-NAME-pretreated and ANG II-preconstricted arterioles was similar to controls without l-NAME treatment. Cinaciguat also induced dilatation in iodinated contrast medium treated AA. Furthermore, it dilated EA, but not AA, after hypoxia/reoxygenation. The results reveal an important role of the NO-sGC-cGMP system for renal dilatation and that EA have a more potent sGC activated dilatory system. Furthermore, AA seem to be more sensitive to hypoxia/reoxygenation than EA under these experimental conditions.

Air pollution and COVID-19 mortality in the United States: Strengths and limitations of an ecological regression analysis.

Assessing whether long-term exposure to air pollution increases the severity of COVID-19 health outcomes, including death, is an important public health objective. Limitations in COVID-19 data availability and quality remain obstacles to conducting conclusive studies on this topic. At present, publicly available COVID-19 outcome data for representative populations are available only as area-level counts. Therefore, studies of long-term exposure to air pollution and COVID-19 outcomes using these data must use an ecological regression analysis, which precludes controlling for individual-level COVID-19 risk factors. We describe these challenges in the context of one of the first preliminary investigations of this question in the United States, where we found that higher historical PM2.5 exposures are positively associated with higher county-level COVID-19 mortality rates after accounting for many area-level confounders. Motivated by this study, we lay the groundwork for future research on this important topic, describe the challenges, and outline promising directions and opportunities.

Evaluating the impact of long-term exposure to fine particulate matter on mortality among the elderly.

Many studies link long-term fine particle (PM2.5) exposure to mortality, even at levels below current U.S. air quality standards (12 micrograms per cubic meter). These findings have been disputed with claims that the use of traditional statistical approaches does not guarantee causality. Leveraging 16 years of data-68.5 million Medicare enrollees-we provide strong evidence of the causal link between long-term PM2.5 exposure and mortality under a set of causal inference assumptions. Using five distinct approaches, we found that a decrease in PM2.5 (by 10 micrograms per cubic meter) leads to a statistically significant 6 to 7% decrease in mortality risk. Based on these models, lowering the air quality standard to 10 micrograms per cubic meter would save 143,257 lives (95% confidence interval, 115,581 to 170,645) in one decade. Our study provides the most comprehensive evidence to date of the link between long-term PM2.5 exposure and mortality, even at levels below current standards.