Radiationless decay spectrum of O 1s double core holes in liquid water.

We present a combined experimental and theoretical investigation of the radiationless decay spectrum of an O 1s double core hole in liquid water. Our experiments were carried out using liquid-jet electron spectroscopy from cylindrical microjets of normal and deuterated water. The signal of the double-core-hole spectral fingerprints (hypersatellites) of liquid water is clearly identified, with an intensity ratio to Auger decay of singly charged O 1s of 0.0014(5). We observe a significant isotope effect between liquid H2O and D2O. For theoretical modeling, the Auger electron spectrum of the central water molecule in a water pentamer was calculated using an electronic-structure toolkit combined with molecular-dynamics simulations to capture the influence of molecular rearrangement within the ultrashort lifetime of the double core hole. We obtained the static and dynamic Auger spectra for H2O, (H2O)5, D2O, and (D2O)5, instantaneous Auger spectra at selected times after core-level ionization, and the symmetrized oxygen-hydrogen distance as a function of time after double core ionization for all four prototypical systems. We consider this observation of liquid-water double core holes as a new tool to study ultrafast nuclear dynamics.

Beta blockers are associated with lower all-cause mortality among HFpEF patients.

BACKGROUND: The evidence regarding beta blocker (BB) benefit in heart failure with preserved ejection fraction (HFpEF) remains inconclusive, leading to consideration of BB withdrawal in this population. OBJECTIVES: In this study, we retrospectively analyzed the association of BB on all-cause mortality in HFpEF patients. METHODS: This is a single-center retrospective cohort study of 20,206 patients with left ventricular ejection fraction (EF) ≥ 50% who were hospitalized with decompensated HF between January 2011 and March 2020. Survival is reported at 30 days, 1 year, and 3 years. A secondary analysis comparing mortality for patients on BB with additional indications including hypertension (HTN), coronary artery disease (CAD), and atrial fibrillation (AF) was completed. Mortality was compared between patients on BB and additional therapies of spironolactone or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs). RESULTS: BB showed lower all-cause mortality at 30 days, 1 year, and 3 years (p < 0.0001). This association with lower all-cause mortality was validated by a supplementary propensity score-matched analysis. At 3 years, there was significant mortality reduction with addition of BB to either spironolactone (p = 0.0359) or ACEi/ARBs (p < 0.0001). CONCLUSION: In a large single-center retrospective registry, BB use was associated with lower mortality in HFpEF patients with a recent decompensated HF hospitalization. The mortality benefit persisted in those treated with spironolactone or ACEi/ARBs, and in those with AF. This provocative data further highlights the uncertainty of the benefit of BB use in this cohort and calls for re-consideration of BB withdrawal, especially in those tolerating it well, without conclusive, large, and randomized trials showing lack of benefit or harm.

Parity violation in resonant inelastic soft x-ray scattering at entangled core holes.

Resonant inelastic x-ray scattering (RIXS) is a major method for investigation of electronic structure and dynamics, with applications ranging from basic atomic physics to materials science. In RIXS applied to inversion-symmetric systems, it has generally been accepted that strict parity selectivity applies in the sub-kilo-electron volt region. In contrast, we show that the parity selection rule is violated in the RIXS spectra of the free homonuclear diatomic O2 molecule. By analyzing the spectral dependence on scattering angle, we demonstrate that the violation is due to the phase difference in coherent scattering at the two atomic sites, in analogy with Young's double-slit experiment. The result also implies that the interpretation of x-ray absorption spectra for inversion symmetric molecules in this energy range must be revised.

Tracking Cavity Formation in Electron Solvation: Insights from X-ray Spectroscopy and Theory.

We present time-resolved X-ray absorption spectra of ionized liquid water and demonstrate that OH radicals, H3O+ ions, and solvated electrons all leave distinct X-ray-spectroscopic signatures. Particularly, this allows us to characterize the electron solvation process through a tool that focuses on the electronic response of oxygen atoms in the immediate vicinity of a solvated electron. Our experimental results, supported by ab initio calculations, confirm the formation of a cavity in which the solvated electron is trapped. We show that the solvation dynamics are governed by the magnitude of the random structural fluctuations present in water. As a consequence, the solvation time is highly sensitive to temperature and to the specific way the electron is injected into water.

X-ray induced ultrafast charge transfer in thiophene-based conjugated polymers controlled by core-hole clock spectroscopy.

We explore ultrafast charge transfer (CT) resonantly induced by hard X-ray radiation in organic thiophene-based polymers at the sulfur K-edge. A combination of core-hole clock spectroscopy with real-time propagation time-dependent density functional theory simulations gives an insight into the electron dynamics underlying the CT process. Our method provides control over CT by a selective excitation of a specific resonance in the sulfur atom with monochromatic X-ray radiation. Our combined experimental and theoretical investigation establishes that the dominant mechanism of CT in polymer powders and films consists of electron delocalisation along the polymer chain occurring on the low-femtosecond time scale.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021.

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

Epidemiology and outcome predictors in 450 patients with hanging-induced cardiac arrest: a retrospective study.

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors. Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period. Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009). Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality.

Backscatter tensor imaging and 3D speckle tracking for simultaneous ex vivo structure and deformation measurement of myocardium.

OBJECTIVE: Biaxial mechanical testing is a common method for elucidation of mechanical properties of excised ventricular myocardium, especially in the context of structural remodeling that accompanies heart disease. Current imaging strategies in biaxial testing are based on optical camera imaging of the tissue surface, thus providing no information about the tissue microstructure and limiting strain measurements to two dimensions. Here, these limitations are overcome by replacing the camera with ultrasound imaging in order to measure both transmural fiber orientation and 3D tissue deformation during biaxial testing. METHODS: Quasi-static biaxial mechanical testing is applied to four samples of excised porcine ventricular myocardium (two left- and two right-ventricular tissues). During testing, a rotational scan of an ultrasound linear array provides data for both backscatter tensor imaging and 3D speckle tracking, from which transmural fiber orientation and tissue deformation are computed, respectively. Ultrasound-derived fiber orientation and tissue strain are validated against histology and camera surface imaging, respectively. DISCUSSION: Ultrasound-derived fiber angle and tissue strain exhibit good accuracy, with root-mean-square errors of 9.9° and 1.2% strain, respectively. Further investigation into the optimization of backscatter tensor imaging is warranted. Replacing the rotational scan of a linear array with volume imaging with a matrix array will improve the technique. CONCLUSION: Ultrasound imaging can replace the optical camera measurement during biaxial mechanical testing of ventricular myocardium in order to accurately provide measurements of transmural fiber orientation and tissue strain. In situ knowledge of transmural fiber structure and tissue deformation can enhance the inverse problem used to determine tissue mechanical properties from biaxial testing.

Pulmonary artery compliance in different forms of pulmonary hypertension.

OBJECTIVE: Pulmonary artery compliance (PAC), estimated as stroke volume (SV) divided by pulmonary artery pulse pressure (PP), may be a predictor of survival in pulmonary arterial hypertension (PAH). Resistance-compliance (RC) time, the product of PAC and pulmonary vascular resistance, is reported to be a physiological constant. We investigated if differences in PAC and RC time exist between pulmonary hypertension (PH) subgroups and examined whether PAC is an independent predictor of transplant-free survival in PAH. METHODS: This was a retrospective analysis of adult PAH (n=532) and chronic thromboembolic PH (CTEPH, n=84) patients enrolled in the US Pulmonary Hypertension Association Registry from 2015 to 2019. PAC and RC time were compared between PH subgroups (connective tissue disease-PAH (CTD-PAH), idiopathic/heritable-PAH (i/h-PAH), drug/toxin-PAH (d/t-PAH)). Cox proportional hazards models were constructed for transplant-free survival, adjusting for REVEAL 2.0 risk score. RESULTS: There were no differences in estimated PAC between PAH subgroups, nor between PAH and CTEPH. RC time was shorter in CTEPH compared with PAH (median 0.55 (IQR 0.45-0.64) vs 0.62 (0.52-0.73) s, p<0.0001). RC time was shortest in CTD-PAH when compared with i/h-PAH and d/t-PAH ((0.59±0.18) vs (0.65±0.20) vs (0.73±0.25) s, p=0.0001). PAC was associated with transplant-free survival (HR 0.72, 95% CI 0.55 to 0.94, p=0.02) but was not an independent predictor of outcome after adjustment for REVEAL 2.0 score. CONCLUSION: PAC was similar between PH groups and was not an independent predictor of transplant-free survival in PAH. RC time was different between PH subgroups, challenging RC time constancy. TRIAL REGISTRATION NUMBER: NCT04071327.

Dynamics of core-excited ammonia: disentangling fragmentation pathways by complementary spectroscopic methods.

Fragmentation dynamics of core-excited isolated ammonia molecules is studied by two different and complementary experimental methods, high-resolution resonant Auger spectroscopy and electron energy-selected Auger electron-photoion coincidence spectroscopy (AEPICO). The combined use of these two techniques allows obtaining information on different dissociation patterns, in particular fragmentation before relaxation, often called ultrafast dissociation (UFD), and fragmentation after relaxation. The resonant Auger spectra contain the spectral signature of both molecular and fragment final states, and therefore can provide information on all events occurring during the core-hole lifetime, in particular fragmentation before relaxation. Coincidence measurements allow correlating Auger electrons with ionic fragments from the same molecule, and relating the ionic fragments to specific Auger final electronic states, and yield additional information on which final states are dissociative, and which ionic fragments can be produced in timescales either corresponding to the core-hole lifetime or longer. Furthermore, we show that by the combined use of two complementary experimental techniques we are able to identify more electronic states of the NH2+ fragment with respect to the single one already reported in the literature.

The Lung Allocation Score Remains Inequitable for Patients with Pulmonary Arterial Hypertension, Even after the 2015 Revision.

Rationale: The lung allocation score (LAS) was revised in 2015 to improve waiting list mortality and rate of transplant for patients with pulmonary arterial hypertension (PAH). Objectives: We sought to determine if the 2015 revision achieved its intended goals. Methods: Using the Standard Transplant Analysis and Research file, we assessed the impact of the 2015 LAS revision by comparing the pre- and postrevision eras. Registrants were divided into the LAS diagnostic categories: group A-chronic obstructive pulmonary disease; group B-pulmonary arterial hypertension; group C-cystic fibrosis; and group D-interstitial lung disease. Competing risk regressions were used to assess the two mutually exclusive competing risks of waiting list death and transplant. Cumulative incidence plots were created to visually inspect risks. Measurements and Main Results: The LAS at organ matching increased by 14.2 points for registrants with PAH after the 2015 LAS revision, the greatest increase among diagnostic categories (other LAS categories: Δ, -0.9 to +2.8 points). Before the revision, registrants with PAH had the highest risk of death and lowest likelihood of transplant. After the 2015 revision, registrants with PAH still had the highest risk of death, now similar to those with interstitial lung disease, and the lowest rate of transplant, now similar to those with chronic obstructive pulmonary disease. Conclusions: Although the 2015 LAS revision improved access to transplant and reduced the risk of waitlist death for patients with PAH, it did not go far enough. Significant differences in waitlist mortality and likelihood of transplant persist.

Alternative Pathway to Double-Core-Hole States.

Excited double-core-hole states of isolated water molecules resulting from the sequential absorption of two x-ray photons have been investigated. These states are formed through an alternative pathway, where the initial step of core ionization is accompanied by the shake-up of a valence electron, leading to the same final states as in the core-ionization followed by core-excitation pathway. The capability of the x-ray free-electron laser to deliver very intense, very short, and tunable light pulses is fully exploited to identify the two different pathways.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Photochemical Ring-Opening Reaction of 1,3-Cyclohexadiene: Identifying the True Reactive State.

The photochemically induced ring-opening isomerization reaction of 1,3-cyclohexadiene to 1,3,5-hexatriene is a textbook example of a pericyclic reaction and has been amply investigated with advanced spectroscopic techniques. The main open question has been the identification of the single reactive state which drives the process. The generally accepted description of the isomerization pathway starts with a valence excitation to the lowest lying bright state, followed by a passage through a conical intersection to the lowest lying doubly excited state, and finally a branching between either the return to the ground state of the cyclic molecule or the actual ring-opening reaction leading to the open-chain isomer. Here, in a joint experimental and computational effort, we demonstrate that the evolution of the excitation-deexcitation process is much more complex than that usually described. In particular, we show that an initially high-lying electronic state smoothly decreasing in energy along the reaction path plays a key role in the ring-opening reaction.

Refraction-corrected backscatter tensor imaging of excised porcine ventricular myocardium.

Backscatter tensor imaging (BTI) is performed on excised porcine right- and left-ventricular myocardium to estimate the transmural myofiber orientation. Calculation of the backscatter spatial coherence employs measured sound speeds of the myocardium and the fluid that separates the tissue from the imaging array to account for effects of refraction during the delay-and-sum beamforming calculation. Compared to the assumption of a homogeneous sound speed in the imaging region, accounting for refraction yields significantly increased average spatial coherence as well as contrast of spatial coherence between the along- and across-fiber directions, thus improving sensitivity of BTI for myofiber orientation estimation.

Anticoagulation in pulmonary arterial hypertension - association with mortality, healthcare utilization, and quality of life: The Pulmonary Hypertension Association Registry (PHAR).

BACKGROUND: Routine long-term anticoagulation in pulmonary arterial hypertension (PAH) is controversial. To date, anticoagulation has been found to be beneficial or neutral in idiopathic disease (IPAH) and neutral-to-harmful in connective tissue disease (CTD-PAH). We sought to examine the association between anticoagulation and mortality, healthcare utilization, and quality of life (QoL) in PAH. METHODS: The PHAR is a prospective registry of PAH patients referred to 58 pulmonary hypertension care centers in the United States. We compared patients who received anticoagulation during enrollment (questionnaire documented) to those who did not. Cox proportional hazard models were used for mortality, Poisson multivariate regression models for healthcare utilization, and generalized estimating equations for QOL RESULTS: Of 1175 patients included, 316 patients were treated with anticoagulation. IPAH/hereditary PAH (HPAH) comprised 46% of the cohort and CTD-PAH comprised 33%. After adjustment for demographics, clinical characteristics, site and disease severity, anticoagulation was not associated with mortality in the overall population (HR, 1.00; 95% CI, 0.72-1.36), IPAH/HPAH (HR, 1.19; 95% CI, 0.74-1.94), or CTD-PAH (HR 0.87; 95% CI, 0.53-1.42). Anticoagulation was associated with an increased rate of emergency department visits (IRR: 1.41), hospitalizations (IRR: 1.30), and hospital days (IRR 1.33). QOL measured by emPHasis-10 score was worse in patients receiving anticoagulation (mean difference 1.74; 95% CI 0.40-3.09). CONCLUSIONS: Anticoagulation is not associated with higher mortality, but is associated with increased healthcare utilization in the PHAR. PAH-specific QoL may be worse in patients receiving anticoagulation. The risks and benefits surrounding routine prescription of anticoagulation for PAH should be carefully considered.

An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension.

Preclinical and early clinical studies suggest that angiotensin-converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin-converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi-center, open-label, exploratory, single-dose, dose-escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.1, 0.2, 0.4, or 0.8 mg/kg. Dose escalation occurred after four or more participants per cohort were dosed and a review of safety, tolerability, pharmacokinetics, and hemodynamic data up to 24 h postdose was undertaken. The primary endpoint was a change in cardiopulmonary hemodynamics (pulmonary vascular resistance, cardiac index, and mean pulmonary artery pressure) from baseline. Secondary/exploratory objectives included safety and tolerability, effect on renin-angiotensin system peptides, and pharmacokinetics. GSK2586881 demonstrated no consistent or sustained effect on acute cardiopulmonary hemodynamics in participants with PAH receiving background PAH therapy (N = 23). All doses of GSK2586881 were well tolerated. GSK2586881 was quantifiable in plasma for up to 4 h poststart of infusion in all participants and caused a consistent and sustained reduction in angiotensin II and a corresponding increase in angiotensin (1-7) and angiotensin (1-5). While there does not appear to be a consistent acute vasodilatory response to single doses of GSK2586881 in participants with PAH, the potential benefits in terms of chronic vascular remodeling remain to be determined.

Recoil lineshapes in hard X-ray photoelectron spectra of large molecules - free and anchored-on-surface 10-aminodecane-1-thiol.

Core-level photoelectron spectroscopy of molecules presents unique opportunities but also challenges in the Hard X-ray Spectroscopy (HAXPES) realm. Here we focus on the manifestation of the photoelectron recoil effects in core-level photoemission spectra, using the independent normal-mode oscillators approach that allows to model and investigate the resulting recoil lineshapes for molecules of large sizes with only a slight computational effort. We model the recoil lineshape for N 1s and C 1s photoemission using the 10-aminodecane-1-thiol molecule as an example. It represents also a class of compounds commonly used in creating self-assembled monolayers (SAMs) on surfaces. Attachment of the -SH head group to the surface is modelled here in a simplified way by anchoring the sulfur atom of a single molecule. The effects of the orientation of photoemission in the molecular frame on the recoil lineshape of such anchored molecules are illustrated and discussed as a possible geometry probe. Time-evolution of the recoil excitations from the initial emission site across the entire molecule is also visualized.