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.

Benralizumab Prevents Recurrent Exacerbations in Patients with Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis.

Exacerbations in chronic obstructive pulmonary disease (COPD), which tend to occur in clusters and increase with disease severity, come with high societal and economic burdens. Prevention and delay of recurrent exacerbations is an unmet and significant therapeutic need for patients with COPD. GALATHEA (NCT02138916) and TERRANOVA (NCT02155660) were trials assessing efficacy of benralizumab in patients with frequent COPD exacerbations despite treatment. Although these studies found that benralizumab given as an add-on treatment did not significantly reduce annual rates of COPD exacerbations after 56 weeks of treatment, in the following exploratory post hoc analysis of the GALATHEA and TERRANOVA trials we identified a potential responder population in which treatment with benralizumab prevents recurrent COPD exacerbations during 30- and 90-day periods following an initial exacerbation, a vulnerable period for an exacerbation to occur. This responder population was characterized by high blood eosinophil counts and frequent previous exacerbations despite optimized triple therapy. These results highlight the importance of targeted therapies for high-risk populations and merit further research into the benefits of biologic therapies for COPD exacerbations.

Pulmonary manifestations and the effectiveness of enzyme replacement therapy in Fabry Disease with the p. Arg227Ter (p.R227*) mutation.

BACKGROUND: Fabry disease (FD) is caused by a defect in α-galactosidase A gene (GLA) which leads to a progressive accumulation of neutral shingolipids, mainly globotriaosylceramide and its metabolites in several organs. Pulmonary manifestations of FD mimic chronic obstructive pulmonary disease and are disproportionate to smoking status. The effect of enzyme replacement therapy (ERT) on pulmonary function is inconclusive. We studied the effect of ERT on pulmonary function in FD with a mutation p. Arg227Ter (p.R227*) which is one of the most common mutations causing classical FD in Finland and worldwide. METHODS: Patients were annually examined by multidisciplinary team. Based on the maximal pulmonary oxygen consumption at the baseline, either cardiopulmonary exercise test or combination of spirometry and 6-minute walking test were performed annually during 5-year follow-up. RESULTS: Four males and eight females met the criteria for ERT and were included in this study. Three of 12 patients had obstruction by GOLD criterion before ERT, and one had a borderline obstruction. In 5 years, five patients were classified as obstructive, although the real change in FEV1/FVC was unchanged in the whole cohort. Only one patient was an active smoker. CONCLUSION: In nonsmokers, pulmonary manifestations in classical FD are mild and might be stabilized by ERT.

Breaking inversion symmetry by protonation: experimental and theoretical NEXAFS study of the diazynium ion, N2H.

As an example of symmetry breaking in NEXAFS spectra of protonated species we present a high resolution NEXAFS spectrum of protonated dinitrogen, the diazynium ion N2H+. By ab initio calculations we show that the spectrum consists of a superposition of two nitrogen 1s absorption spectra, each including a π* band, and a nitrogen 1s to H+ charge transfer band followed by a weak irregular progression of high energy excitations. Calculations also show that, as an effect of symmetry breaking by protonation, the π* transitions are separated by 0.23 eV, only slightly exceeding the difference in the corresponding dark (symmetry forbidden) and bright (symmetry allowed) core excitations of neutral N2. By DFT and calculations and vibrational analysis, the complex π* excitation band of N2H+ is understood as due to the superposition of the significantly different vibrational progressions of excitations from terminal and central nitrogen atoms, both leading to bent final state geometries. We also show computationally that the electronic structure of the charge transfer excitation smoothly depends on the nitrogen-proton distance and that there is a clear extension of the spectra going from infinity to close nitrogen-proton distance where fine structures show some, although not fully detailed, similarities. An interesting feature of partial localization of the nitrogen core orbitals, with a strong, non-monotonous, variation with nitrogen-proton distance could be highlighted. Specific effects could be unraveled when comparing molecular cation NEXAFS spectra, as represented by recently recorded spectra of N2+ and CO+, and spectra of protonated molecules as represented here by the N2H+ ion. Both types containing rich physical effects not represented in NEXAFS of neutral molecules because of the positive charge, whereas protonation also breaks the symmetry. The effect of the protonation on dinitrogen can be separated in charge, which extends the high-energy part of the spectrum, and symmetry-breaking, which is most clearly seen in the low-energy π* transition.

How often segmentectomy is feasible in lung cancer surgery: a population-based evaluation.

OBJECTIVES: Despite promising outcomes in lung cancer surgery, segmentectomy has not gained wide acceptance at the population level. Our aim was to evaluate the potential role of segmentectomy in real-world practice. METHODS: All patients diagnosed with lung cancer and operated between January 2013 and December 2019 in Central Finland and Ostrobothnia were included. This intent-to-treat analysis sub-grouped segmentectomy patients by indications: (i) high-risk patients with stage I disease (n = 40), (ii) ≤20 mm ground-glass opacity (n = 12), (iii) carcinoid (n = 12), (iv) special indication (n = 20) including synchronous and metachronous disease, fissure-crossing tumour, and synchronous other solid cancers requiring surgery, (v) solid ≤2 cm tumour (n = 14) in medically fit patient. To evaluate the potential role of segmentectomy, all preoperative CT scans were re-evaluated. RESULTS: Of 269 patients, in 98 (36.4%) intention of surgery was segmentectomy. Indication was high risk in 40 (14.9%), ground-glass opacity in 12 (4.5%), carcinoid in 12 (4.5%), special indication in 20 (7.4%) and ≤2 cm solid tumour in medically fit patients in 14 (5.2%). The major complication rate was ≤15% in all groups with excellent 3-year recurrence-free survival between 76.5% and 100%. Segmentectomy could have been technically potential in up to 46.8% of patients. This was exactly the rate performed in the last 3-year period of this study. CONCLUSIONS: Performed and potential segmentectomy rates underline the importance of adaptation of this technique with possibility to offer curative surgery to many high risk and special patients with low morbidity and mortality.

Association of performance in a stair-climbing test with complications and survival after lung cancer resection in the video-assisted thoracoscopic surgery era: population-based outcomes.

INTRODUCTION: With a population-based cohort in the video-assisted thoracoscopic surgery (VATS) era, we aimed to evaluate the value of the stair-climbing test (SCT) on short- and long-term outcomes of lung cancer surgery. METHODS: All patients operated due to primary lung cancer in Central Finland and Ostrobothnia from 2013 to June 2020 were included. For the analysis, clinical variables including the outcome of SCT and cause-specific mortality were available. Short- and long-term outcomes were compared between <11 m (n=66) and >12 m SCT (n=217) groups. RESULTS: Patients with poor performance (<11 m) had more comorbidities and worse lung function but did not differ in tumour stage or treatment. No differences between groups were observed in major morbidity rate (10.6% versus 11.1%, p=0.918) or median hospital stay (5 (IQR 4-7) versus 4 (IQR 3-7), p=0.179). At 1-year, fewer patients were alive and living at home in the climbing <11 m group (81.3%) compared to the >12 m group (94.2%), p=0.002. No difference was observed in cancer-specific 5-year survival. Non-cancer-specific survival (62.9% versus 83.1%, p<0.001) and overall survival (49.9% versus 70.0%, p<0.001) were worse in the <11 m group. After adjustment for confounding factors, SCT remained as a significant predictor for non-cancer-specific (HR 4.28; 95% CI 2.10-8.73) and overall mortality (HR 2.38; 95% CI 1.43-3.98). CONCLUSIONS: With SCT-based exercise testing, VATS can be performed safely, with a similar major morbidity rate in the poor performance group (<11 m) compared to >12 m group. Poor exercise performance increases non-cancer-specific mortality. Being a major predictor of survival, exercise capacity should be included in prognostic models.

Low-cost exercise interventions improve long-term cardiometabolic health independently of a family history of type 2 diabetes: a randomized parallel group trial.

INTRODUCTION: To investigate the effect of an exercise prescription and a 1-year supervised exercise intervention, and the modifying effect of the family history of type 2 diabetes (FH), on long-term cardiometabolic health. RESEARCH DESIGN AND METHODS: For this prospective randomized trial, we recruited non-diabetic participants with poor fitness (n=1072, 30-70 years). Participants were randomly assigned with stratification for FH either in the exercise prescription group (PG, n=144) or the supervised exercise group (EG, n=146) group and compared with a matched control group from the same population study (CON, n=782). The PG and EG received exercise prescriptions. In addition, the EG attended supervised exercise sessions two times a week for 60 min for 12 months. Cardiometabolic risk factors were measured at baseline, 1 year, 5 years, and 6 years. The CON group received no intervention and was measured at baseline and 6 years. RESULTS: The EG reduced their body weight, waist circumference, diastolic blood pressure, and low-density lipoprotein-cholesterol (LDL-C) but not physical fitness (p=0.074) or insulin or glucose regulation (p>0.1) compared with the PG at 1 year and 5 years (p≤0.011). The observed differences were attenuated at 6 years; however, participants in the both intervention groups significantly improved their blood pressure, high-density lipoprotein-cholesterol, and insulin sensitivity compared with the population controls (p≤0.003). FH modified LDL-C and waist circumference responses to exercise at 1 year and 5 years. CONCLUSIONS: Low-cost physical activity programs have long-term beneficial effects on cardiometabolic health regardless of the FH of diabetes. Given the feasibility and low cost of these programs, they should be advocated to promote cardiometabolic health. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02131701.

Extended resections and other special cases in lung cancer surgery: Real-world population-based outcomes.

BACKGROUND: Lung cancer invading outside a lobe centrally or peripherally, or presenting with synchronous or metachronous tumors, requires a special approach. Here, we aimed to evaluate the rate and outcomes of surgery of these patients in a medium-volume practice using real-world, population-based data. METHODS: All patients (n = 269) on whom lung cancer surgery was performed in Central Finland and Ostrobothnia between January 2013 and December 2019 were included. A total of 40 patients with sleeve (n = 18) or other extended resections (n = 9), multifocal diseases (n = 14), and other operated synchronous cancers (n = 3) required an extended or otherwise special surgical approach (extended group). Short- and long-term outcomes were compared to high-risk (n = 72) and normal patient groups (n = 157). RESULTS: The rate of extended resection was 14.9%. The rates of PET-CT (95%), invasive staging (35%), and brain imaging (42.5%) were highest in extended group compared to other groups. Extended group had larger and higher rate of stage III tumors than high-risk and normal groups. All extended group patients underwent anatomic lung resection with better lymph node yield than the other two groups, with a neoadjuvant and/or adjuvant treatment rate of 70.0%. Major complications occurred in 7.5% in the extended group, 19.4% in the high-risk group, and 6.4% in the normal group; at one year, alive and living at home rates were 88.2%, 83.3%, and 97.8%, and overall five-year survival rates 75.6%, 62.4%, and 63.9% (P = 0.287), respectively. CONCLUSIONS: After guideline-based evaluation, a significant rate of these special cases can be resected with a low complication rate and good long-term survival in real-world practice. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Extended resections for lung cancer include tumors spreading outside the lung The rate of extended resection was 14.9% in a population-based setting Major complications occurred in 7.5% and five-year survival was 75.6% What this study adds Complication rate and long-term outcome were similar compared to normal patients Guideline-based evaluation results with excellent outcome in real-world practice.

The carbon and oxygen K-edge NEXAFS spectra of CO.

We present and analyze high resolution near edge X-ray absorption fine structure (NEXAFS) spectra of CO+ at the carbon and oxygen K-edges. The spectra show a wealth of features that appear very differently at the two K-edges. The analysis of these features can be divided into three parts; (i) repopulation transition to the open shell orbital - here the C(1s) or O(1s) to 5σ transition, where the normal core hole state is reached from a different initial state and different interaction than in X-ray photoelectron spectroscopy; (ii) spin coupled split valence bands corresponding to C(1s) or O(1s) to π* transitions; (iii) remainder weak and long progressions towards the double ionization potentials containing a manifold of peaks. These parts, none of which has correspondence in NEXAFS spectra of neutral molecules, are dictated by the localization of the singly occupied 5σ orbital, adding a dimension of chemistry to the ionic NEXAFS technique.

Energy-Dependent Relative Cross Sections in Carbon 1s Photoionization: Separation of Direct Shake and Inelastic Scattering Effects in Single Molecules.

We demonstrate that the possibility of monitoring relative photoionization cross sections over a large photon energy range allows us to study and disentangle shake processes and intramolecular inelastic scattering effects. In this gas-phase study, relative intensities of the carbon 1s photoelectron lines from chemically inequivalent carbon atoms in the same molecule have been measured as a function of the incident photon energy in the range of 300-6000 eV. We present relative cross sections for the chemically shifted carbon 1s lines in the photoelectron spectra of ethyl trifluoroacetate (the "ESCA" molecule). The results are compared with those of methyl trifluoroacetate and S-ethyl trifluorothioacetate as well as a series of chloro-substituted ethanes and 2-butyne. In the soft X-ray energy range, the cross sections show an extended X-ray absorption fine structure type of wiggles, as was previously observed for a series of chloroethanes. The oscillations are damped in the hard X-ray energy range, but deviations of cross-section ratios from stoichiometry persist, even at high energies. The current findings are supported by theoretical calculations based on a multiple scattering model. The use of soft and tender X-rays provides a more complete picture of the dominant processes accompanying photoionization. Such processes reduce the main photoelectron line intensities by 20-60%. Using both energy ranges enabled us to discern the process of intramolecular inelastic scattering of the outgoing electron, whose significance is otherwise difficult to assess for isolated molecules. This effect relates to the notion of the inelastic mean free path commonly used in photoemission studies of clusters and condensed matter.

Electronic structure dynamics in a low bandgap polymer studied by time-resolved photoelectron spectroscopy.

Means to measure the temporal evolution following a photo-excitation in conjugated polymers are a key for the understanding and optimization of their function in applications such as organic solar cells. In this paper we study the electronic structure dynamics by direct pump-probe measurements of the excited electrons in such materials. Specifically, we carried out a time-resolved photoelectron spectroscopy (TRPES) study of the polymer PCPDTBT by combining an extreme ultraviolet (XUV) high harmonic generation source with a time-of-flight spectrometer. After excitation to either the 1st excited state or to a higher excited state, we follow how the electronic structure develops and relaxes on the electron binding energy scale. Specifically, we follow a less than 50 fs relaxation of the higher exited state and a 10 times slower relaxation of the 1st excited state. We corroborate the results using DFT calculations. Our study demonstrates the power of TRPES for studying photo-excited electron energetics and dynamics of solar cell materials.

Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes.

Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release.

Radial extracorporeal shockwave therapy compared with manual therapy in runners with iliotibial band syndrome.

BACKGROUND: Although different conservative treatment options have been proposed, there is a paucity of research on the management of iliotibial band syndrome (ITBS) in runners. OBJECTIVE: To compare two treatment protocols for ITBS; radial shockwave therapy (RSWT) and manual therapy (ManT). Both therapies were administered concurrently with an exercise rehabilitation programme. METHODS: The study was designed as a randomised controlled clinical trial. Twenty-four runners with ITBS received 3 treatments at weekly intervals of either RSWT (n= 11) or ManT (n= 13). In addition, all subjects followed an exercise programme for at least 4 weeks. Main outcome measures were established as mean differences (MD) in pain during treadmill running. RESULTS: There was no significant difference in pain reduction between the two interventions at 4 weeks (p= 0.796), and 8 weeks (p= 0.155) follow-up. Thus, both groups reported similar magnitude of reduced pain during the intervention (p= 0.864). The shockwave therapy (SWT) group reported a 51% decrease in pain at week 4 (p= 0.022), and a 75% decrease at week 8 (p= 0.004). The ManT group showed a 61% reduction in pain at week 4 (p= 0.059), and a 56% reduction at week 8 (p= 0.067). CONCLUSIONS: RSWT and ManT were equally effective in reducing pain in subjects with ITBS.

Surface behavior of hydrated guanidinium and ammonium ions: a comparative study by photoelectron spectroscopy and molecular dynamics.

Through the combination of surface sensitive photoelectron spectroscopy and molecular dynamics simulation, the relative surface propensities of guanidinium and ammonium ions in aqueous solution are characterized. The fact that the N 1s binding energies differ between these two species was exploited to monitor their relative surface concentration through their respective photoemission intensities. Aqueous solutions of ammonium and guanidinium chloride, and mixtures of these salts, have been studied in a wide concentration range, and it is found that the guanidinium ion has a greater propensity to reside at the aqueous surface than the ammonium ion. A large portion of the relative excess of guanidinium ions in the surface region of the mixed solutions can be explained by replacement of ammonium ions by guanidinium ions in the surface region in combination with a strong salting-out effect of guanidinium by ammonium ions at increased concentrations. This interpretation is supported by molecular dynamics simulations, which reproduce the experimental trends very well. The simulations suggest that the relatively higher surface propensity of guanidinium compared with ammonium ions is due to the ease of dehydration of the faces of the almost planar guanidinium ion, which allows it to approach the water-vapor interface oriented parallel to it.

A multi purpose source chamber at the PLEIADES beamline at SOLEIL for spectroscopic studies of isolated species: cold molecules, clusters, and nanoparticles.

This paper describes the philosophy and design goals regarding the construction of a versatile sample environment: a source capable of producing beams of atoms, molecules, clusters, and nanoparticles in view of studying their interaction with short wavelength (vacuum ultraviolet and x-ray) synchrotron radiation. In the design, specific care has been taken of (a) the use standard components, (b) ensuring modularity, i.e., that swiftly switching between different experimental configurations was possible. To demonstrate the efficiency of the design, proof-of-principle experiments have been conducted by recording x-ray absorption and photoelectron spectra from isolated nanoparticles (SiO2) and free mixed clusters (Ar/Xe). The results from those experiments are showcased and briefly discussed.

Molecular sinkers: X-ray photoemission and atomistic simulations of benzoic acid and benzoate at the aqueous solution/vapor interface.

In this work, we provide a detailed microscopic picture of the behavior of benzoic acid at the aqueous solution/vapor interface in its neutral as well as in its dissociated form (benzoate). This is achieved through a combination of highly surface-sensitive X-ray photoelectron spectroscopy experiments and fully atomistic molecular simulations. We show that significant changes occur in the interface behavior of the neutral acid upon release of the proton. The benzoic acid molecules are found to be strongly adsorbed at the interface layer with the planes of the aromatic rings oriented almost parallel to the water surface. In contrast, in the benzoate form, the carboxylate group shows a sinker-like behavior while the aromatic ring acts as a buoy, oriented nearly perpendicular to the surface. Furthermore, a significant fraction of the molecular ions move from the interface layer into the bulk of the solution. We rationalize these findings in terms of the very different hydration properties of the carboxylic group in the two charge states. The molecule has an amphiphilic nature, and the deprotonation thus changes the hydrophobic/hydrophilic balance between the nonpolar aromatic and the polar carboxylic parts of the molecule. That, consequently, leads to a pronounced reorientation and depletion of the molecules at the interface.

The protonation state of small carboxylic acids at the water surface from photoelectron spectroscopy.

We report highly surface sensitive core-level photoelectron spectra of small carboxylic acids (formic, acetic and butyric acid) and their respective carboxylate conjugate base forms (formate, acetate and butyrate) in aqueous solution. The relative surface propensity of the carboxylic acids and carboxylates is obtained by monitoring their respective C1s signal intensities from a solution in which their bulk concentrations are equal. All the acids are found to be enriched at the surface relative to the corresponding carboxylates. By monitoring the PE signals of acetic acid and acetate as a function of total concentration, we find that the protonation of acetic acid is nearly complete in the interface layer. This is in agreement with literature surface tension data, from which it is inferred that the acids are enriched at the surface while (sodium) formate and acetate, but not butyrate, are depleted. For butyric acid, we conclude that the carboxylate form co-exists with the acid in the interface layer. The free energy cost of replacing an adsorbed butyric acid molecule with a butyrate ion at 1.0 M concentration is estimated to be >5 kJ mol(-1). By comparing concentration dependent surface excess data with the evolution of the corresponding photoemission signals it is furthermore possible to draw conclusions about how the distribution of molecules that contribute to the excess is altered with bulk concentration.

Quantitative analysis of [11C]AZ10419369 binding to 5-HT1B receptors in human brain.

A novel radioligand for positron emission tomography (PET) imaging of serotonin 5-HT(1B) receptors, [(11)C]AZ10419369, has been recently described. In this study, the potential for quantitative analysis of [(11)C]AZ10419369 binding to central 5-HT(1B) receptors was evaluated in human subjects. PET measurements were performed after injection of [(11)C]AZ10419369 in 10 subjects. Data were analyzed with kinetic modeling and linear graphical analysis using the arterial plasma as input function, and with reference tissue models using cerebellar cortex as the reference region. Binding of [(11)C]AZ10419369 was highest in pallidum, ventral striatum, and occipital cortex and lowest in cerebellum. The percentage of unchanged radioligand in plasma was 97% to 99%, indicating that no significant amounts of radioactive metabolites were formed during the time of analysis. Time-activity curves of [(11)C]AZ10419369 could be described with both one-tissue compartment (1-TC) and two-tissue compartment (2-TC) models in the majority of subjects. The 2-TC model failed to deliver reasonable estimates of the kinetic parameters. However, stable estimates of binding potential (BP(ND)) were obtained by constraining K(1)/k(2) to the distribution volume obtained with the 1-TC model in the cerebellar cortex. BP(ND) values estimated with reference tissue models were correlated with the corresponding values obtained with kinetic modeling. The findings support the use of reference tissue models in applied clinical studies with [(11)C]AZ10419369.

Circularly polarized x rays: another probe of ultrafast molecular decay dynamics.

Dissociative nuclear motion in core-excited molecular states leads to a splitting of the fragment Auger lines: the Auger-Doppler effect. We present here for the first time experimental evidence for an Auger-Doppler effect following F1s → a(1g)* inner-shell excitation by circularly polarized x rays in SF(6). In spite of a uniform distribution of the dissociating S-F bonds near the polarization plane of the light, the intersection between the subpopulation of molecules selected by the core excitation with the cone of dissociation induces a strong anisotropy in the distribution of the S-F bonds that contributes to the scattering profile measured in the polarization plane.

Photoinduced formation of N2 molecules in ammonium compounds.

Via fluorescence yield (FY) and resonant inelastic scattering spectroscopy in the soft X-ray range we find that soft X-rays induce formation of N2 molecules in solid NH4Cl and in related compounds. The nitrogen molecules form weak bonds in NH4Cl, so that a substantial fraction of the molecules remains in the sample. From measurements of the FY as a function of exposure and temperature, the rates for the photochemical processes are estimated. At elevated temperatures (363 K), several nitrogen atoms are removed from the sample per incoming photon. At lower temperatures (233 K), the rate is reduced to around 0.02 nitrogen atoms for each incoming photon. Virtually all these atoms form N2 molecules which are bound in the sample. The generality and implications of these results are briefly discussed.