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Background/Introduction No firm prospective evidence exists on the long-term course of disease-specific and generic quality of life (QoL) or their determinants in patients with acute pulmonary embolism (PE). Reliable data on this topic is essential for early identification of patients at risk of deviating from the expected course and prevention of clinical events affecting QoL recovery after PE. Purpose We examined the two-year course of QoL and the impact of events occurring after the acute phase of PE in patients from the prospective multicentre FOllow-up after aCUte pulmonary emboliSm (FOCUS) study. Methods All patients with complete QoL assessment at 3, 12 and 24 months (N=462) were included in the analysis of the two-year course of QoL; all patients with QoL assessment at 12 months, 24 months, or both (N=740) contributed to a multivariable linear mixed-effects regression for the investigation of determinants of long-term QoL. Disease-specific QoL was assessed with the Pulmonary Embolism Quality of Life (PEmb-QoL) instrument (global score: 0 = best, 100 = worst QoL), generic health-related QoL with the Euro Quality of life group (EuroQol) five-dimensions utility index (EQ-5D-5L; 0 = worst, 1 = best QoL) and the EuroQol visual analogue scale (0 = worst, 100 = best QoL). Incident events (recurrent PE, bleeding, stroke, new cancer diagnosis, and re-hospitalization) were modelled as time-varying covariates from discharge to month 12 and from month 12 to month 24. Results Among 462 patients with complete QoL assessment [200 (43.3%) women, median age 61.5 (IQR: 49–72) years, high-risk PE 15/462 (3.2%)], the median (IQR) PEmb-QoL score at 3, 12, and 24 months was 20 (9–36), 14 (5–30) and 13 (5–28), with a similar trend across all sub-dimensions (Figure 1); the mean (95% CI) EQ-5D-5L utility index 0.86 (0.84–0.88), 0.88 (0.87–0.90) and 0.87 (0.85–0.89); the mean (95% CI) EuroQoL visual analogue scale 74.2 (72.5–75.9), 76.8 (75.2–78.4) and 76.3 (74.6–78.0). Upon multivariable analysis in 740 patients with QoL data at 12 or 24 months, QoL according to all three scales was worse in women, patients of older age, with cardiopulmonary disease, with higher BMI, and in smokers, but did not change significantly at 24 vs 12 months. Incident PE recurrence or stroke did not considerably affect any of the QoL dimensions, whereas re-hospitalization for any cause worsened disease-specific QoL, a new cancer diagnosis worsened both scales of generic QoL, and bleeding worsened generic QoL as assessed by the Visual Analogue Scale (Table 1). Conclusion Generic and disease-specific QoL after PE improved in the first year and then plateaued in the second year. Disease-specific QoL was adversely affected by re-hospitalization for any cause but was robust to new cancer diagnosis and bleedings, which instead worsened generic QoL. These findings may support long-term management of patients with PE and contribute to design and interpretation of interventional studies. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Health Care

Background In pulmonary arterial hypertension (PAH), there is an excessive respiratory drive, which leads to inefficient ventilation with subsequent hypocapnia. Changes in blood gas analysis (BGA) may correlate with symptom severity and outcome. Data on impact of targeted PAH therapy on BGA are scarce and it remains unclear if these values can be used for risk stratification purposes. Purpose To assess capillary BGA in PAH at diagnosis and to evaluate the effect of targeted therapy on classical and calculated BGA parameters. Methods 147 patients (62.3±17.1 years; female/male ratio: 66.7/33.3%) with newly diagnosed PAH were treated with targeted PAH therapy. 12-month follow-up included assessment of capillary blood gases and clinical variables. Patients underwent repeat RHC after 15.9±15.5 months. Results At diagnosis, both pcO2 (66.8±1.3 mmHg) and pcCO2 (32.7±0.5 mmHg) were slightly reduced. At 12-month follow-up, pcCO2 increased significantly to values within normal range (35.3±0.4 mmHg), while pcO2 showed no significant changes. After using the formula to calculate standard pcO2, baseline values were even lower, but there were significant improvements at 12-month follow-up, also reaching normal values. Changes in pcCO2 and standard pcO2 at diagnosis correlated with hemodynamics and survival at follow-up. Repeated RHC demonstrated significant reductions in mean PAP (48.9±1.2 to 39.9±1.0 mmHg; −18.4%), and PVR (11.3±0.7 to 6.2±0.3 WU; −45.1%), and an increase in cardiac index (2.1±0.04 to 2.6±0.1 ml/min/m2; +23.8%) (all p Conclusions Targeted PAH therapy leads to significantly improved cardiopulmonary hemodynamics with subsequent increase in pcCO2, presumably due to less hyperventilation. Changes in pcCO2 and standard pcO2 (but not pcO2) correlate with hemodynamics and survival, potentially serving as non-invasive parameters for risk assessment and therapeutic response. The discrepancy between pcO2 and standard pcO2 at diagnosis suggests that pcO2 is upregulated by the hyperventilatory state. Standard pcO2 represents an easy-to-calculate parameter that can help more accurately identify PAH patients requiring O2 therapy in addition to targeted therapy. Further studies are needed in this context. Funding Acknowledgement Type of funding sources: None.

Background/Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be a late complication of acute pulmonary embolism (PE). However, up to one third of CTEPH patients do not report prior symptomatic venous thromboembolism (VTE). Furthermore, a substantial proportion of patients presenting with an acute PE event may exhibit radiological signs of chronicity at baseline computed tomography pulmonary angiography (CTPA). Purpose To determine the prevalence of baseline radiological parameters indicating chronic thrombosis or pulmonary hypertension, and ultimately pre-existing CTEPH, among patients with acute PE enrolled in the prospective multicentre Follow-Up after Acute Pulmonary Embolism (FOCUS) cohort study. Methods Patients with acute symptomatic PE and absence of a known history of CTEPH, enrolled at two large FOCUS centres, were included. The assessment of index CTPA scans was conducted by two independent expert radiologists who were unaware of the clinical characteristics and the follow-up data of the patients. CTPA parameters indicating chronicity were prespecified on the basis of recently proposed criteria in the literature. A third independent expert radiologist provided an assessment in case of disagreement between the first two. Baseline radiological data were prospectively validated with the aid of two-year prospective clinical follow-up data focusing on CTEPH and the post-PE syndrome (co-primary outcomes of the FOCUS study). Results A total of 303 patients (median age: 63 years, 44.6% women) were included. In >95% of the patients, the expert radiologists could confirm signs of acute PE at baseline CTPA. Radiological signs of chronic thrombi or pulmonary hypertension at baseline were detected in 46 (15.2%) patients. In 8 patients, the expert radiologists agreed on the presence of pre-existing CTEPH based on their interpretation of the overall radiological pattern. During follow-up, five (1.7%; 95% CI 0.7–3.8%) of 303 patients were diagnosed with CTEPH, over a median time of 95 days after baseline. Four of them were among the 8 patients in whom the radiological experts suspected pre-existing CTEPH at baseline, and among the 46 patients in whom CTPA findings suggesting chronic thrombi or chronic pulmonary hypertension were present at baseline. The use of the predefined individual parameters of chronicity from the literature also helped identifying patients with chronic disease, and could be used as a tool for screening acute PE patients for pre-existing CTEPH. Conclusion A substantial proportion of patients who are diagnosed with CTEPH during follow-up after acute PE may already have pre-existing CTEPH at the time of the index event. An intensified follow-up programme and focussed screening for CTEPH should be considered in patients with signs of chronicity at baseline CTPA. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Health Care

Background Proliferation and phenotypic modulation of vascular smooth muscle cells (SMCs) significantly contribute to the functionality of the aortic wall. Dysregulation of underlying signal transduction pathways impairs the vessel wall structure and promote the development and progression of abdominal aortic aneurysms (AAA). The PI 3-kinase (PI3K) isoform p110α is activated downstream of receptor tyrosine kinases (RTKs) and represents the most relevant PI3K isoform in SMCs. Aim This project follows the hypothesis that p110α deficiency impairs proliferation and phenotypic modulation of SMCs as well as the structure of the extracellular matrix (ECM) and therefore promotes the development and progression of AAA. It was investigated how p110α deficiency affects the plasticity of SMCs, the production and structure of ECM components, and the formation of AAA. Methods and results Western blot analyses showed that SMCs isolated from smooth muscle specific p110α−/− (sm-p110α−/−) mice were characterized by decreased expression of the differentiation markers sm-α-actin, calponin and sm-MHC. Mechanistically, phosphorylation of key modulators of the SMC phenotype – AKT1, AKT2, FOXO1, -3 and -4 as well as GSK3β – was impaired in p110α−/− SMCs after RTK stimulation. These findings indicate that phenotypic modulation of p110α−/− SMCs is restricted. In addition, protein expression of elastin and fibrillin was reduced in p110α−/− SMCs. In silico analysis (MatLab macro CT-FIRE and Curvalign) of the ECM produced by SMCs in vitro revealed a significantly reduced elastin fiber length and width in p110α−/− SMCs compared to fibers produced by WT SMCs (p Conclusion p110α deficiency in SMCs impairs aortic wall structure and promotes the development and progression of aortic aneurysms. Mechanistically, p110α activity maintains a differentiated SMC phenotype as well as the expression and assembly of ECM components. These data identify p110α signaling as a modifiable target for preventive and therapeutic strategies for aortic aneurysms. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

Rationale Pulmonary hypertension (PH) is a pulmonary vascular disease characterised by chronically elevated pulmonary arterial mean pressure, increased pulmonary vascular resistance and right ventricular (RV) dysfunction and hypertrophy. The pathogenesis includes vasoconstriction of pulmonary vessels and pulmonary vascular remodelling. Phosphatidylinositol 3'-kinase γ (PI3Kγ) is highly expressed in leukocytes, endothelial cells (EC) and cardiomyocytes, which are involved in the pathogenesis of PH. The catalytic function of PI3Kγ has been shown to be associated with numerous processes that are potentially important for both vascular remodelling and maladaptive cardiac hypertrophy, including leukocyte recruitment and endothelial cell proliferation and survival. However, inhibition of non-catalytic PI3Kγ function results in reduced nitric oxide (NO) production by endothelial NO synthase (eNOS), which may lead to increased vascular resistance. Therefore, the aim of our study was to investigate the role of both catalytic and non-catalytic PI3Kγ functions in the pathogenesis of PH. Methods The importance of PI3Kγ in the pathogenesis of PH was analysed in vivo using the hypoxia-induced mouse model of PH (21 days at 10% O2 hypoxia (HOX)). PI3Kγ knockout mice (PI3Kγ−/−), as well as mice expressing a catalytically inactive form of PI3Kγ (PI3KγKD/KD) were investigated. To specifically inhibit the non-catalytic function of PI3Kγ, C57BL/6N mice were treated with a blocking peptide via intratracheal instillation and studied in the same model. Subsequently, systolic right ventricular pressure (RVSP) was measured using a Millar pressure catheter inserted via the jugular vein. In vitro, western blotting was used to investigate the phosphorylation of eNOS (Ser1177) in pulmonary ECs from wild type (WT), PI3Kγ−/− and PI3KγKD/KD mice. Results PI3Kγ−/− mice showed significantly increased RVSP after three weeks of hypoxia compared with WT controls (HOX WT 34.16±3.47mmHg vs. HOX PI3Kγ−/− 37.04±2.43mmHg; p=0.005; n≥7). A significant increase in RVSP was also detected in PI3KγKD/KD and blocking peptide-treated mice (HOX WT 34.67±2.02mmHg vs. HOX PI3KγKD/KD 37.95±1.39mmHg; p=0.023; n≥5 and HOX vehicle 34.19±2.74mmHg vs. HOX blocking peptide 37.61±2.46mmHg; p=0.011; n≥9). Heart rate, as well as systemic blood pressure, remained unchanged. Under normoxic conditions, no difference in RVSP between the groups could be measured. Interestingly, western blot detected reduced phosphorylation of eNOS after stimulation with fetal calf serum in PI3Kγ−/− ECs compared to WT and PI3KγKD/KD. Conclusion These results show that blunting of both catalytic and non-catalytic functions of PI3Kγ in vivo do not prevent the pathogenesis of PH, but conversely enhance hypoxia-induced elevation of RVSP. In this context, reduced phosphorylation of eNOS may play a crucial role, leading to increased vasoconstriction. Additional studies are required to evaluate the underlying mechanisms in detail. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): DFG Deutsche Forschungsgemeinschaft

Lead halide perovskites exhibit structural instabilities and large atomic fluctuations thought to impact their optical and thermal properties, yet detailed structural and temporal correlations of their atomic motions remain poorly understood. Here, these correlations are resolved in CsPbBr3 crystals using momentum-resolved neutron and X-ray scattering measurements as a function of temperature, complemented with first-principles simulations. We uncover a striking network of diffuse scattering rods, arising from the liquid-like damping of low-energy Br-dominated phonons, reproduced in our simulations of the anharmonic phonon self-energy. These overdamped modes cover a continuum of wave vectors along the edges of the cubic Brillouin zone, corresponding to two-dimensional sheets of correlated rotations in real space, and could represent precursors to proposed two-dimensional polarons. Further, these motions directly impact the electronic gap edge states, linking soft anharmonic lattice dynamics and optoelectronic properties. These results provide insights into the highly unusual atomic dynamics of halide perovskites, relevant to further optimization of their optical and thermal properties. Neutron and X-ray scattering measurements provide further insight into the anharmonic behaviour of lead halide perovskites, revealing that rotations of PbBr6 octahedra in CsPbBr3 crystals occur in a correlated fashion along two-dimensional planes.

Tetragonal tungsten bronze (TTB) based oxides constitute a large family of dielectric materials which are known to exhibit complex distortions producing incommensurately modulated superstructures as well as significant local deviations from their average symmetry. The local deviations produce diffuse scattering in diffraction experiments. The structure as well as the charge dynamics of these materials are anticipated to be sensitive to defects, such as cation or oxygen vacancies. In this work, in an effort to understand how the structural and charge dynamical properties respond to these two types of vacancy defects, we have performed measurements of dielectric susceptibilities and single crystal diffraction experiments of two types of TTB materials with both ‘filled’ (Ba2NdFeNb4O15 and Ba2PrFeNb4O15) and ‘unfilled’ (Sr0.5Ba0.5Nb2O6) cation sublattices. We also perform these measurements before and after oxygen annealing, which alters the oxygen vacancy concentrations. Surprisingly, we find that many of the diffuse scattering features that are present in the unfilled structure are also present in the filled structure, suggesting that the random fields and disorder that are characteristic of the unfilled structure are not responsible for many of the local structural features that are reflected in the diffuse scattering. Oxygen annealing clearly affected both color and dielectric properties, consistent with a diminishment of the oxygen vacancy concentration, but had little effect on observed diffuse patterns.

The recent reports of superconductivity in Nd(1–x)Sr(x)NiO(2)/SrTiO(3) heterostructures have reinvigorated interest in potential superconductivity of low-oxidation state nickelates. Synthesis of Ni(1+)-containing compounds is notoriously difficult. In the current work, a combined sol-gel combustion and high-pressure annealing technique was employed to prepare polycrystalline perovskite Nd(1–x)Sr(x)NiO(3) (x = 0, 0.1, and 0.2). Metal nitrates and metal acetates were used as starting materials, and the latter were found to be superior to the former in terms of safety and reactivity. The Nd(1–x)Sr(x)NiO(3) compounds were subsequently reduced to Nd(1–x)Sr(x)NiO(2) using calcium hydride in a sealed, evacuated quartz tube. To understand the synthesis pathway, the evolution from NdNiO(3) to NdNiO(2) was monitored using in situ synchrotron x-ray diffraction during the reduction process. Electrical transport properties were consistent with an insulator-metal transition occurring between x = 0 and 0.1 for Nd(1–x)Sr(x)NiO(3). Superconductivity was not observed in our bulk samples of Nd(1–x)Sr(x)NiO(2). Neutron diffraction experiments at 3 and 300 K were performed on Nd(0.9)Sr(0.1)NiO(2), in which no magnetic Bragg reflections were observed, and the results of structural Rietveld refinement are provided.

We investigate the spin-glass transition in the strongly frustrated well-known compound $Fe_2TiO_5$. A remarkable feature of this transition, widely discussed in the literature, is its anisotropic properties: the transition manifests itself in the magnetic susceptibly only along one axis, despite $Fe^{3+}$ $d^5$ spins having no orbital component. We demonstrate, using neutron scattering, that below the transition temperature $T_g = 55 K$, $Fe_2TiO_5$ develops nanoscale surfboard shaped antiferromagnetic regions in which the $Fe^{3+}$ spins are aligned perpendicular to the axis which exhibits freezing. We show that the glass transition may result from the freezing of transverse fluctuations of the magnetization of these regions and we develop a mean-field replica theory of such a transition, revealing a type of magnetic van der Waals effect., 14 pages, 4 figures, 6 page supplemental material, 2 figures

BACKGROUND: Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality.METHODS: Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) was an open-label, randomised controlled trial in 81 hospital-based pulmonary hypertension centres in 22 countries. The study enrolled patients aged 18-75 years with symptomatic PAH at intermediate risk of 1-year mortality (based on the European Society for Cardiology-European Respiratory Society guideline thresholds for WHO functional class and 6-min walk distance [6MWD]) who were receiving treatment with a PDE5i with or without an endothelin receptor antagonist for at least 6 weeks before randomisation. Patients were excluded if they had been previously treated with riociguat, had used prostacyclin analogues or prostacyclin receptor agonists within 30 days before randomisation, had clinically significant restrictive or obstructive parenchymal lung disease, or had left heart disease. Patients were randomly assigned (1:1) to remain on PDE5i treatment (oral sildenafil [≥60 mg per day] or oral tadalafil [20-40 mg per day]; the PDE5i group) or to switch to oral riociguat (up to 2·5 mg three times per day; the riociguat group), using an interactive voice and web response system, stratified by cause of PAH. The primary endpoint was clinical improvement by week 24, defined as an absence of clinical worsening and prespecified improvements in at least two of three variables (6MWD, WHO functional class, and N-terminal prohormone of brain natriuretic peptide), analysed using last observation carried forward in all randomly assigned patients with observed values at baseline and week 24 who received at least one dose of study medication (the full analysis set). Secondary endpoints included clinical worsening events. The trial has been completed and is registered with ClinicalTrials.gov, NCT02891850.FINDINGS: Between Jan 11, 2017, and July 31, 2019, 293 patients were screened, of which 226 patients were randomly assigned to the riociguat group (n=111) or to the PDE5i group (n=115). 211 patients completed the study and 14 patients discontinued (seven in each group). One patient assigned to the PDE5i group did not receive treatment, so 225 patients were included in the safety analysis, and one further patient in the PDE5i group had missing components of the composite primary endpoint at baseline, so 224 patients were included in the full analysis set. The primary endpoint was met by 45 (41%) of 111 patients in the riociguat group and 23 (20%) of 113 patients in the PDE5i group; odds ratio [OR] 2·78 (95% CI 1·53-5·06; p=0·0007). Clinical worsening events occurred in one (1%) of 111 patients in the riociguat group (hospitalisation due to worsening PAH) and 10 (9%) of 114 patients in the PDE5i group (hospitalisation due to worsening PAH [n=9]; disease progression [n=1]; OR 0·10 [0·01-0·73]; p=0·0047). The most frequently occurring adverse events were hypotension (15 [14%]), headache (14 [13%]), and dyspepsia (10 [9%]) in the riociguat group, and headache (eight [7%]), cough (seven [6%]), and upper respiratory tract infection (seven [6%]) in the PDE5i group. Serious adverse events were reported in eight (7%) of 111 patients in the riociguat group and 19 (17%) of 114 patients in the PDE5i group. During the study, four patients died in the PDE5i group, one of them during the safety follow-up period.INTERPRETATION: Switching to riociguat from PDE5i treatment, both of which act via the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway, could be a strategic option for treatment escalation in patients with PAH at intermediate risk of 1-year mortality.FUNDING: Bayer AG, Merck Sharp & Dohme.

The discovery of a rotational symmetry breaking, or nematic, state in the superconducting doped topological insulator MxBi2Se3 (M = Cu, Sr, Nb) indicates a multicomponent superconducting order parameter which is topological. Many questions remain in this family of materials. In particular, the nematic axis of twofold symmetry is always pinned along one of three rotationally equivalent directions in the threefold symmetric basal plane in the rhombohedral crystal. Crystallographic strain has been proposed as the origin of the choice of pinning axis. Here, we discuss nematic pinning of the superconducting state, summarizing our magnetotransport, magnetization, penetration depth, and calorimetry measurements, which support the theoretical picture of topological superconductivity. We discuss the impact of controlled disorder via proton irradiation on the nematic superconducting state and discuss results of our multimodal technique for searching for crystallographic strain below 1 K via simultaneous diffraction and magnetotransport measurements.

We report inelastic x-ray scattering measurements of the in-plane polarized transverse acoustic phonon mode propagating along $q\ensuremath{\parallel}[100]$ in various hole-doped compounds belonging to the 122 family of iron-based superconductors. The slope of the dispersion of this phonon mode is proportional to the square root of the shear modulus ${C}_{66}$ in the $q\ensuremath{\rightarrow}0$ limit and, hence, sensitive to the tetragonal to orthorhombic structural phase transition occurring in these compounds. In contrast to a recent report for $\mathrm{Ba}{({\mathrm{Fe}}_{0.94}{\mathrm{Co}}_{0.06})}_{2}{\mathrm{As}}_{2}$ [Weber et al., Phys. Rev. B 98, 014516 (2018)], we find qualitative agreement between values of ${C}_{66}$ deduced from our experiments and those derived from measurements of the Young modulus in ${\mathrm{Ba}}_{1\ensuremath{-}x}{(\mathrm{K},\mathrm{Na})}_{x}{\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ at optimal doping. These results provide an upper limit of about 50 \AA{} for the nematic correlation length for the investigated optimally hole-doped compounds. Furthermore, we also studied compounds at lower doping levels exhibiting the orthorhombic magnetic phase, where ${C}_{66}$ is not accessible by volume probes, as well as the ${C}_{4}$ tetragonal magnetic phase.

The recent reports of superconductivity in Nd1-x Sr x NiO2/SrTiO3 heterostructures have reinvigorated interest in potential superconductivity of low-oxidation state nickelates. Synthesis of Ni1+-containing compounds is notoriously difficult. In the current work, a combined sol-gel combustion and high-pressure annealing technique was employed to prepare polycrystalline perovskite Nd1-x Sr x NiO3 (x = 0, 0.1, and 0.2). Metal nitrates and metal acetates were used as starting materials, and the latter were found to be superior to the former in terms of safety and reactivity. The Nd1-x Sr x NiO3 compounds were subsequently reduced to Nd1-x Sr x NiO2 using calcium hydride in a sealed, evacuated quartz tube. To understand the synthesis pathway, the evolution from NdNiO3 to NdNiO2 was monitored using in situ synchrotron x-ray diffraction during the reduction process. Electrical transport properties were consistent with an insulator-metal transition occurring between x = 0 and 0.1 for Nd1-x Sr x NiO3. Superconductivity was not observed in our bulk samples of Nd1-x Sr x NiO2. Neutron diffraction experiments at 3 and 300 K were performed on Nd0.9Sr0.1NiO2, in which no magnetic Bragg reflections were observed, and the results of structural Rietveld refinement are provided.

Lead halide perovskites exhibit structural instabilities and large atomic fluctuations thought to impact their optical and thermal properties, yet detailed structural and temporal correlations of their atomic motions remain poorly understood. Here, these correlations are resolved in CsPbBr

The anomalous Hall effect (AHE) is an intriguing transport phenomenon occurring typically in ferromagnets as a consequence of broken time reversal symmetry and spin-orbit interaction. It can be caused by two microscopically distinct mechanisms, namely, by skew or side-jump scattering due to chiral features of the disorder scattering, or by an intrinsic contribution directly linked to the topological properties of the Bloch states. Here we show that the AHE can be artificially engineered in materials in which it is originally absent by combining the effects of symmetry breaking, spin orbit interaction and proximity-induced magnetism. In particular, we find a strikingly large AHE that emerges at the interface between a ferromagnetic manganite (La0.7Sr0.3MnO3) and a semimetallic iridate (SrIrO3). It is intrinsic and originates in the proximity-induced magnetism present in the narrow bands of strong spin-orbit coupling material SrIrO3, which yields values of anomalous Hall conductivity and Hall angle as high as those observed in bulk transition-metal ferromagnets. These results demonstrate the interplay between correlated electron physics and topological phenomena at interfaces between 3d ferromagnets and strong spin-orbit coupling 5d oxides and trace an exciting path towards future topological spintronics at oxide interfaces., The anomalous Hall effect (AHE) occurs in ferromagnets caused by intrinsic and extrinsic mechanisms. Here, Yoo et al. report large anomalous Hall conductivity and Hall angle at the interface between a ferromagnet La0.7Sr0.3MnO3 and a semimetallic SrIrO3, due to the interplay between correlated physics and topological phenomena.

LaNiO3&minus, &delta, single crystals have been obtained via high pressure floating zone growth under 149 bar of oxygen pressure. We find a radial gradient in the magnetic properties of specimens extracted from the as-grown boule, which we correlate with the appearance of ordered oxygen vacancy structures. This radial oxygen inhomogeneity has been characterized systematically using a combination of magnetization and X-ray scattering measurements. We establish the presence of rhombohedral ( R 3 &macr, c ), oxygen stoichiometric specimens at the periphery of the boule and the presence of a dilute concentration of ordered oxygen-deficient orthorhombic La2Ni2O5 in the center. Furthermore, we demonstrate that the as-grown, oxygen-deficient central regions of the crystal can be annealed under high oxygen pressure, without loss of crystallinity, into fully oxygenated LaNiO3, recovering magnetic properties that are characteristic of stoichiometric specimens from the exterior region of the crystal. Thus, single crystals of LaNiO3&minus, possess oxygen content that can be reversibly modified under oxidizing and reducing conditions.

Herzinsuffizienz ist mit hoher Sterblichkeit, haufigen Krankenhausaufnahmen, schlechter Lebensqualitat und steigenden Kosten assoziiert. Trotz Fortschritten bei medikamentosen und Device-basieren Therapien bleiben Mortalitat und Morbiditat nach Ersthospitalisierung wegen akuter kardialer Dekompensation (AKD) hoch. In randomisierten Studien, die den Wert verschiedener Formen des nichtinvasiven Telemonitorings pruften, wurden Hospitalisierungen wegen AKD selten vermindert, weil klinische Zeichen und Symptome keine fruhen Indikatoren der AKD darstellen, sodass bei ihrem Auftreten stationare Behandlungen oft schon unvermeidbar sind. Unter verschiedenen implantierbaren Monitoring-Devices erwies sich in den USA das drahtlose Telemonitoring des pulmonalarteriellen Drucks (PAP) mit dem CardioMEMS™-Sensor (Abbott, Sylmar, Kalifornien, USA) als sicher und klinisch effektiv. Bei so uberwachten Patienten wurden – unabhangig von der kardialen Pumpfunktion – Hospitalisierungen wegen AKD deutlich reduziert, weil die Fruherkennung hamodynamischer Dekompensationen an einem PAP-Anstieg noch vor Auftreten klinischer Symptome eine praventive Therapieanpassung ermoglichte. Derzeit wird diese Technologie auch in Europa erprobt. Die Leitlinie der Europaischen Gesellschaft fur Kardiologie empfiehlt, bei Risikopatienten die Implantation eines CardioMEMS™-Sensors zu erwagen (Klasse IIb-B). Technische Weiterentwicklungen implantierbarer Systeme erlauben z. B. die Druckmessung im linken Vorhof, die erweiterte Nutzung hamodynamischer Daten (z. B. kontinuierliche Druckmessung) oder eine Selbstuberwachung durch Patienten mit einem interaktiven Modul. Anwendungsbreite und Bedeutung druckgefuhrter Therapien werden in Zukunft absehbar weiter wachsen mit der reellen Chance einer effektiveren Vermeidung von klinischen Ereignissen auch in Risikopopulationen.

A number of praseodymium-containing cobalt perovskites undergo temperature-dependent metal-insulator transitions that involve a transfer of electrons between cobalt and praseodymium cations. We have used high-resolution inelastic x-ray scattering to directly measure the changes in the acoustic phonon dispersion through this transition in one such single crystal, ${(\mathrm{P}{\mathrm{r}}_{0.85}{\mathrm{Y}}_{0.15})}_{0.7}\mathrm{C}{\mathrm{a}}_{0.3}\mathrm{Co}{\mathrm{O}}_{3\ensuremath{-}\ensuremath{\delta}}$, in an effort to understand the role of the lattice in the transition. Transverse and acoustic modes were measured in the pseudocubic (200), (220), and (222) zones both above and below the transition temperature. The resultant dispersion curves reveal that the transition is associated with a significant hardening of the pseudocubic ${C}_{11}$ elastic constant, whereas ${C}_{12}$ and ${C}_{44}$ do not significantly change. Analysis of the temperature-dependent damping of the longitudinal acoustic mode in the (200) zone reveals a peak in the damping at temperatures just above the transition temperature. Significant elastic diffuse scattering is also observed above the transition temperature, likely resulting from clusters in which the electron transfer is beginning to occur as a precursor to the phase transition. The presence of these clusters likely limits the phonon lifetimes, thus leading to the observed damping.

Disorder is generically anticipated to suppress long range charge density wave (CDW) order. We report transport, thermodynamic, and scattering experiments on Pd$_x$ErTe$_3$, a model CDW system with disorder induced by intercalation. The pristine parent compound ($x=0$) shows two separate, mutually perpendicular, incommensurate unidirectional CDW phases setting in at 270 K and 165 K. Here we track the suppression of signatures corresponding to these two parent transitions as the Pd concentration increases. At the largest values of $x$, we observe complete suppression of long range CDW order in favor of superconductivity. We also report evidence from electron and x-ray diffraction which suggests a tendency toward short-range ordering along both wavevectors which persists even well above the crossover temperature. Pd$_x$ErTe$_3$ provides a promising model system for the study of the interrelation of charge order and superconductivity in the presence of quenched disorder., Comment: 9 pages, 7 figures

Heart failure (HF) is an emerging epidemic associated with significant morbidity and mortality, impaired quality of life and high healthcare costs. Despite major advances in pharmacological and device-based therapies, mortality and morbidity have remained high after an index hospitalization for acute cardiac decompensation (ACD). Randomized trials evaluating various forms of noninvasive telemonitoring failed to improve rehospitalization rates in such patients, possibly due to lack of sensitivity of clinical signs and symptoms as early indicators of HF. Among different implantable monitoring devices, wireless remote monitoring of the pulmonary artery pressure (PAP) with the CardioMEMS™ sensor (Abbott, Sylmar, CA, USA) has been shown to be safe and clinically effective in the USA. The patients showed substantial reductions in hospital admissions for ACD, irrespective of left ventricular pump function, because PAP-guided HF management facilitates timely recognition of incipient ACD and appropriate modification of medical treatment before hospitalization becomes unavoidable. These encouraging results have also stimulated evaluation of this novel technology outside the USA. Studies are also underway in Europe and European HF guidelines recommend considering implantation of a CardioMEMS™ sensor in high-risk patients (class IIb-B). More technologically refined implantable hemodynamic monitoring systems allowing, for example, left atrial pressure measurements, are under development. Promising novel approaches to using information from such devices include continuous hemodynamic monitoring and patient self-management based on the pressure information. Thus, pressure-guided HF management is likely to further expand in the future and may help improve clinical outcomes also in high-risk HF populations.

The family of rare-earth ($R$) tritellurides $R\mathrm{T}{\mathrm{e}}_{3}$ features charge-density-wave (CDW) order related to strongly momentum-dependent electron-phonon coupling. Similar to other CDW compounds, superconductivity is observed when the CDW order is suppressed via hydrostatic pressure [J. J. Hamlin et al., Phys. Rev. Lett. 102, 177002 (2009)]. What sets the heavier members of the $R\mathrm{T}{\mathrm{e}}_{3}$ series apart is the observation of a second CDW transition at lower temperatures having an in-plane ordering wave vector ${q}_{\mathrm{CDW},2}\ensuremath{\parallel}[100]$ of almost the same magnitude but orthogonal to the ordering wave vector ${q}_{\mathrm{CDW},1}\ensuremath{\parallel}[001]$ observed at higher temperatures [N. Ru et al., Phys. Rev. B 77, 035114 (2008)]. Here, we report an inelastic x-ray scattering investigation of the lattice dynamics of $\mathrm{DyT}{\mathrm{e}}_{3}$ In particular, we show that there are several phonon modes along both in-plane directions, which respond to the onset of the CDW transition at ${T}_{\mathrm{CDW},1}=308\phantom{\rule{4pt}{0ex}}\mathrm{K}$. Surprisingly, these soft modes close to ${q}_{\mathrm{CDW},2}=(0.68,0,0)$ show strong softening near ${T}_{\mathrm{CDW},1}$ but do not exhibit any response to the lower-temperature transition at ${T}_{\mathrm{CDW},2}=68\phantom{\rule{4pt}{0ex}}\mathrm{K}$. Our results indicate that the low-temperature CDW order is not just the 90\ifmmode^\circ\else\textdegree\fi{} rotated analogue of the one appearing at high temperatures.

Die erhohte Aufmerksamkeit gegenuber der pulmonalen Hypertonie (PH) fuhrt dazu, dass diese haufiger und zunehmend auch bei alteren Patienten, die vermehrt unter Begleiterkrankungen leiden, diagnostiziert wird. Bei Vorliegen einer PH und einer Lungen- oder Linksherzerkrankung muss differenziert werden, ob die Linksherz- oder Lungenerkrankung die Ursachen einer meist milden PH sind oder unabhangige Komorbiditaten. Zudem kann ein Schlafapnoesyndrom zur PH und umgekehrt eine schwere PH zur zentralen Schlafapnoe fuhren. Die Befundinterpretation ist anspruchsvoll, erfordert Erfahrung, eine komplette hamodynamische Evaluierung, die Bildgebung sowie die Bewertung von Lungenfunktion und Spiroergometrie. Sie sollte immer unter Einbeziehung eines Expertenzentrums erfolgen. Sowohl beim Vorliegen einer Lungenfibrose, einer COPD mit und ohne Lungenemphysem als auch bei Linksherzinsuffizienz hat der gleichzeitige Nachweis einer PH eine negative prognostische Bedeutung. Gleichwohl konnte bisher in kontrollierten Studien nicht belegt werden, dass eine Senkung des pulmonalarteriellen Drucks (PAP) zu einer signifikanten Verbesserung von Belastbarkeit oder Prognose fuhrt. Eine gezielte medikamentose PH-Therapie ist bisher nicht zugelassen. Die Therapie der Grunderkrankung steht im Vordergrund. Nach Korrektur einer Mitralklappeninsuffizienz und unter nichtinvasiver Beatmung (NIPPV) bei alveolarer Hypoventilation ist mit einer hamodynamischen und funktionellen Verbesserung zu rechnen. Bei der diastolischen Linksherzinsuffizienz zielt die Therapie auf eine Optimierung des Flussigkeitsstatus. Patienten mit PH und Linksherz- oder Lungenerkrankungen sollten klinischen Studien zugefuhrt werden.

Since its discovery in 2014, the magnetic tetragonal ${C}_{4}$ phase has been identified in a growing number of hole-doped 122 Fe-based superconducting compounds. Exhibiting a unique double-Q magnetic structure and a strong competition with both superconducting and magnetic order parameters, the ${C}_{4}$ phase and the conditions of its formation are of significant interest to understanding the fundamental mechanisms in these materials. Particularly, separating the importance of direct changes to the relative size of hole and electron pockets at the Fermi surface (achieved via charge doping) from the role of structural changes due to differences of ionic radii of dopants is useful to determine the underlying parameter which causes the ${C}_{4}$ instability. Here, we report the discovery of the ${C}_{4}$ phase in a fourth member of the hole-doped 122 materials ${\mathrm{Ca}}_{\text{1-x}}{\mathrm{Na}}_{\text{x}}{\mathrm{Fe}}_{\text{2}}{\mathrm{As}}_{\text{2}}\phantom{\rule{4pt}{0ex}}(0.20\ensuremath{\le}x\ensuremath{\le}0.50)$ as determined from neutron and x-ray powder diffraction studies. The maximum of the ${C}_{4}$ dome is observed at $x=0.44$ with a reentrant temperature ${T}_{r}=52$ K and an extent of $\mathrm{\ensuremath{\Delta}}x\ensuremath{\sim}0.07$ in composition. It is observed that for a range of compositions within the ${C}_{4}$ dome $(0.40\ensuremath{\le}x\ensuremath{\le}0.42$), there is a second reentrance $({T}_{{r}_{2}}\phantom{\rule{4pt}{0ex}}l\phantom{\rule{4pt}{0ex}}{T}_{r})$ where the antiferromagnetic ${C}_{2}$ phase is recovered---a feature previously only seen in ${\mathrm{Ba}}_{\text{1-x}}{\mathrm{K}}_{\text{x}}{\mathrm{Fe}}_{\text{2}}{\mathrm{As}}_{\text{2}}$. A phase diagram is presented for ${\mathrm{Ca}}_{\text{1-x}}{\mathrm{Na}}_{\text{x}}{\mathrm{Fe}}_{\text{2}}{\mathrm{As}}_{\text{2}}$ and compared to the other $\mathrm{Na}$-doped 122's---${A}_{\text{1-x}}{\mathrm{Na}}_{\text{x}}{\mathrm{Fe}}_{\text{2}}{\mathrm{As}}_{\text{2}}$ with $A$ = Ba, Sr, and Ca. The structural parameters for these three systems are compared and the importance of the ``chemical pressure'' due to changing the $A$-site ion ($A$ = Ba, Sr, Ca) is discussed.

Die pulmonale Hypertonie (PH) ist ein haufiges Phanomen, welches als Folge verschiedener Erkrankungen (z. B. Herzinsuffizienz, chronische Lungenerkrankungen, Lungenembolie), als eigenstandige Erkrankung der kleinen Lungengefase oder als Mischform auftreten kann. Unabhangig von der Genese ist eine PH bedeutsam fur die Symptomatik und die Prognose. Eine exakte Diagnose und Klassifikation sowie das Verstandnis der hamodynamischen Zusammenhange bieten die Grundlage fur haufig diffizile Therapieentscheidungen. Kurzlich fand die 5. Weltkonferenz zur PH in Nizza statt, auf der wichtige Standards und Definitionen festgelegt bzw. aktualisiert wurden. Die wichtigsten Ergebnisse sowie die Einordnung neuer Therapieoptionen werden in diesem Artikel zusammengefasst.

The competition between superconductivity and other ground states of solids is one of the challenging topics in condensed matter physics. Apart from high-temperature superconductors [1,2] this interplay also plays a central role in the layered transition-metal dichalcogenides, where superconductivity is stabilized by suppressing charge-density-wave order to zero temperature by intercalation [3] or applied pressure [4-7]. 1T-TiSe$_2$ forms a prime example, featuring superconducting domes on intercalation as well as under applied pressure. Here, we present high energy-resolution inelastic x-ray scattering measurements of the CDW soft phonon mode in intercalated Cu$_x$TiSe$_2$ and pressurized 1T-TiSe$_2$ along with detailed ab-initio calculations for the lattice dynamical properties and phonon-mediated superconductivity. We find that the intercalation-induced superconductivity can be explained by a solely phonon-mediated pairing mechanism, while this is not possible for the superconducting phase under pressure. We argue that a hybridization of phonon and exciton modes in the pairing mechanism is necessary to explain the full observed temperature-pressure-intercalation phase diagram. These results indicate that 1T-TiSe$_2$ under pressure is close to the elusive state of the excitonic insulator.

We present a high-energy-resolution inelastic x-ray scattering data investigation of the charge-density-wave (CDW) soft phonon mode upon entering the superconducting state in $2H\text{\ensuremath{-}}\mathrm{NbS}{\mathrm{e}}_{2}$. Measurements were done close to the CDW ordering wave vector ${\mathbit{q}}_{\mathrm{CDW}}$ at $\mathbit{q}={\mathbit{q}}_{\mathrm{CDW}}+(0,0,l),0.15\ensuremath{\le}l\ensuremath{\le}0.5$, for $T=10\phantom{\rule{0.28em}{0ex}}\mathrm{K}$ (CDW order) and $3.8\phantom{\rule{0.28em}{0ex}}\mathrm{K}$ (CDW order+superconductivity). We observe changes of the phonon line shape that are characteristic for systems with strong electron-phonon coupling in the presence of a superconducting energy gap $2{\mathrm{\ensuremath{\Delta}}}_{c}$ and from which we can demonstrate an $l$ dependence of the superconducting gap. Reversely, our data imply that the CDW energy gap is strongly localized along the $c$* direction. The confinement of the CDW gap to a very small momentum region explains the rather low competition and easy coexistence of CDW order and superconductivity in $2H\text{\ensuremath{-}}\mathrm{NbS}{\mathrm{e}}_{2}$. However, the energy gained by opening ${\mathrm{\ensuremath{\Delta}}}_{\mathrm{CDW}}$ seems to be too small to be the driving force of the phase transition at ${T}_{\mathrm{CDW}}=33\phantom{\rule{0.28em}{0ex}}\mathrm{K}$, which is better described as an electron-phonon coupling driven structural phase transition.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more common forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern because of limited ressources and the need to base treatments on scientific evidence. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, representing an unmet need of targeted PH therapies. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, several working groups were initiated, one of which was specifically dedicated to PH associated with left heart disease. This article summarizes the results and recommendations of this working group.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the targeted therapy of PAH. This article summarizes the results and recommendations of the working group on targeted treatment of PAH.

X-ray diffraction was employed to study the evolution of the charge density wave (CDW) in Cu_{x}TiSe_{2} as a function of copper intercalation in order to clarify the relationship between the CDW and superconductivity. The results show a CDW incommensuration arising at an intercalation value coincident with the onset of superconductivity at around x=0.055(5). Additionally, it was found that the charge density wave persists to higher intercalant concentrations than previously assumed, demonstrating that the CDW does not terminate inside the superconducting dome. A charge density wave peak was observed in samples up to x=0.091(6), the highest copper concentration examined in this study. The phase diagram established in this work suggests that charge density wave incommensuration may play a role in the formation of the superconducting state.

Intracranial infectious aneurysms are rare but hazardous complications of an infective endocarditis. To date, there are no evidence-based recommendations for the treatment of patients with this condition. Therefore, it remains an interdisciplinary challenge to decide which treatment steps are required and in which order they should be carried out. To illustrate the interdisciplinary dilemma in the treatment of these patients, we here present a case of a 23-year-old, drug-addicted woman with infectious endocarditis. While antibiotic treatment of the streptococcus-mitis-induced endocarditis stabilized the overall status of the patient, rupture of a basilar artery aneurysm caused her sudden death. We discuss the decision-making processes of the treatment, potential difficulties and dilemmas when dealing with patients suffering from infectious endocarditis and infectious intracranial aneurysm. Based upon case reports, studies and reviews, we present the options and risks of conservative, neurosurgical, endovascular, and cardiosurgical treatment of intracranial infectious aneurysms, and propose a patient-centered, interdisciplinary treatment concept.