Two-dimensional overdamped fluctuations of the soft perovskite lattice in CsPbBr3.

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.

Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects.

The ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all experiments (5 Escherichia coli, 2 Klebsiella pneumoniae, and 1 Proteus mirabilis). MICs were performed via agar dilution. Urinary bactericidal titers (UBTs) were performed via modified Schlichter test using participant's drug-free urine as the diluent. Urinary time-kill analyses were performed on pooled 24-h urine aliquots from days 1 and 5. All experiments were performed in triplicate with and without the addition of 25 mg/liter of glucose-6-phosphate (G6P). Mean 24-h urine concentrations of fosfomycin ranged from 324.7 to 434.6 mg/liter regardless of study day or dosing regimen. The urinary antibacterial activity of fosfomycin was also similar across study days and dosing regimens. UBT values did not correlate with MICs determined in the presence of G6P. Fosfomycin was reliably bactericidal in urine only against the 5 E. coli strains, regardless of genotype or MIC value. Together, these data do not support the use of oral fosfomycin tromethamine for pathogens other than E. coli or at a dosing frequency higher than QOD. Fosfomycin MICs determined in the presence of G6P may not accurately reflect the in vivo activity given the lack of G6P in human urine. (This study has been registered at ClinicalTrials.gov under identifier NCT02570074.).

Deep inspirations attenuate postprandial airway inflammation in college-aged adults with elevated baseline exhaled nitric oxide: A pilot study.

Airway inflammation (assessed by exhaled nitric oxide (eNO)) increases after a single high-fat meal (HFM), yet this response may be modified by airway stretch and baseline eNO level.Purpose: The purpose of this study was to investigate whether deep inspirations (DIs) would attenuate airway inflammation post-HFM and whether this is modulated by baseline eNO level.Methods: A total of sixteen healthy college-aged participants completed a randomized cross-over study with 8 lower eNO (14.8 ± 2.0 ppb: 3 M/5F; age: 22.0 ± 2.2 yrs) and 8 higher eNO (29.3 ± 11.6 ppb 5 M/3F; age: 22.5 ± 2.6 yrs) participants. All participants completed a control (CON) condition (no DIs pre-HFM) and DI condition (60 DI's to total lung capacity immediately pre-HFM) after an overnight fast. The primary outcome was eNO. Participants had 20 minutes to consume the HFM (1 g fat/1 kg body weight) and eNO was performed at 2- and 4- hours post-HFM. To determine whether baseline eNO levels impacted the effect of DI's, a median split was performed on their baseline eNO level.Results: There was a significant increase in eNO as a main effect of time (p < 0.001). However when analyzing the potential effect of baseline eNO, there was no significant increase in eNO post-HFM in the higher eNO group in the DI condition (p = 0.54). DIs modified the eNO response to a HFM in the group with a higher baseline eNO value.Conclusions: These data display a possible bronchoprotective protect of DIs against postprandial airway inflammation in participants with higher initial eNO level.

The relation of local order to material properties in relaxor ferroelectrics.

Correlating electromechanical and dielectric properties with nanometre-scale order is the defining challenge for the development of piezoelectric oxides. Current lead (Pb)-based relaxor ferroelectrics can serve as model systems with which to unravel these correlations, but the nature of the local order and its relation to material properties remains controversial. Here we employ recent advances in diffuse scattering instrumentation to investigate crystals that span the phase diagram of PbMg1/3Nb2/3O3-xPbTiO3 (PMN-xPT) and identify four forms of local order. From the compositional dependence, we resolve the coupling of each form to the dielectric and electromechanical properties observed. We show that relaxor behaviour does not correlate simply with ferroic diffuse scattering; instead, it results from a competition between local antiferroelectric correlations, seeded by chemical short-range order, and local ferroic order. The ferroic diffuse scattering is strongest where piezoelectricity is maximal and displays previously unrecognized modulations caused by anion displacements. Our observations provide new guidelines for evaluating displacive models and hence the piezoelectric properties of environmentally friendly next-generation materials.

Spin Stripe Order in a Square Planar Trilayer Nickelate.

Trilayer nickelates, which exhibit a high degree of orbital polarization combined with an electron count (d^{8.67}) corresponding to overdoped cuprates, have been identified as a promising candidate platform for achieving high-T_{c} superconductivity. One such material, La_{4}Ni_{3}O_{8}, undergoes a semiconductor-insulator transition at ∼105 K, which was recently shown to arise from the formation of charge stripes. However, an outstanding issue has been the origin of an anomaly in the magnetic susceptibility at the transition and whether it signifies the formation of spin stripes akin to single layer nickelates. Here we report single crystal neutron diffraction measurements (both polarized and unpolarized) that establish that the ground state is indeed magnetic. The ordering is modeled as antiferromagnetic spin stripes that are commensurate with the charge stripes, the magnetic ordering occurring in individual trilayers that are essentially uncorrelated along the crystallographic c axis. A comparison of the charge and spin stripe order parameters reveals that, in contrast to single-layer nickelates such as La_{2-x}Sr_{x}NiO_{4} as well as related quasi-2D oxides including manganites, cobaltates, and cuprates, these orders uniquely appear simultaneously, thus demonstrating a stronger coupling between spin and charge than in these related low-dimensional correlated oxides.

Key inflammatory pathways underlying vascular remodeling in pulmonary hypertension.

Independent of the underlying cause, pulmonary hypertension (PH) remains a devastating condition that is characterized by limited survival. Cumulating evidence indicates that in addition to a dysbalance of mediators regulating vascular tone and growth factors promoting vascular remodeling, failure to resolve inflammation and altered immune processes play a pivotal role in the development and progression of PH. Here, we highlight the role of key inflammatory pathways in the pathobiology of vascular remodeling and PH, and discuss potential therapeutic interventions that may halt disease progression or even reverse pulmonary vascular remodeling. Perivascular inflammation is present in all forms of PH, and inflammatory pathways involve numerous mediators and cell types including macrophages, neutrophils, T cells, dendritic cells, and mast cells. Dysfunctional bone morphogenic protein receptor 2 (BMPR2) signaling and dysregulated immunity enable the accumulation of macrophages and other inflammatory cells in obliterative vascular lesions. Regulatory T cells (Tregs) were shown to be of particular relevance in the control of inflammatory responses. Key cytokines/chemokines include interleukin-6, functioning via classic or trans-signaling, macrophage migratory inhibitory factor (MIF), but also other mediators such as neutrophil-derived myeloperoxidase. The expanding knowledge on this topic has resulted in multiple opportunities for sophisticated therapeutic interventions.

Pulmonary hypertension in HFpEF and HFrEF: Pathophysiology, diagnosis, treatment approaches.

Pulmonary hypertension (PH) is a frequent hemodynamic condition that is highly prevalent in patients with heart failure and reduced (HFrEF) or preserved ejection fraction (HFpEF). Irrespective of left ventricular EF, the presence of PH and right ventricular (RV) dysfunction are highly relevant for morbidity and mortality in patients with heart failure. While elevated left-sided filling pressures and functional mitral regurgitation primarily lead to post-capillary PH, current guidelines and recommendations distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH), the latter being defined by a pulmonary vascular resistance (PVR) of ≥3 Wood units. Here, we describe the pathophysiology and clinical relevance of these distinct entities, and report on the diagnostic work-up including remote pulmonary artery pressure (PAP) monitoring. Furthermore, we highlight strategies to manage PH and improve RV function in heart failure, which may include optimized management of HFrEF and HFpEF (medical and interventional), sufficient volume control, catheter-based mitral valve repair, and-in selected cases-targeted PH therapy. In this context, we also highlight gaps in evidence and the need for further research.

Pulmonary hypertension and valvular heart disease.

Pulmonary hypertension (PH) is an important contributor to morbidity and mortality in patients with left-sided heart disease, including valvular heart disease. In this context, elevated left atrial pressure primarily leads to the development of post-capillary PH. Despite the fact that repair of left-sided valvular heart disease by surgical or interventional approaches will improve PH, recent studies have highlighted that PH (pre- or post-interventional) remains an important predictor of long-term outcome. Here, we review the current knowledge on PH in valvular heart disease taking into account new hemodynamic PH definitions, and the distinction between post- and pre-capillary components of PH. A specific focus is on the precise characterization of hemodynamics and cardiopulmonary interaction, and on potential strategies for the management of residual PH after mitral or aortic valve interventions. In addition, we highlight the clinical significance of tricuspid regurgitation, which may occur as a primary condition or as a consequence of PH and right heart dilatation (functional). In this context, proper patient selection for potential tricuspid valve interventions is crucial. Finally, the article highlights gaps in evidence, and points toward future perspectives.

Low clinical conversion rate in clinically isolated syndrome patients - diagnostic benefit of McDonald 2010 criteria?

BACKGROUND AND PURPOSE: New diagnostic criteria of multiple sclerosis (MS) increase the number of patients being diagnosed with MS whilst a substantial part might not convert to clinically definite MS (CDMS). The diagnostic accuracy of the McDonald 2005 and 2010 criteria for conversion to CDMS was evaluated in an unselected cohort of patients in whom an MS diagnostic work-up was decided. METHODS: Clinical, magnetic resonance imaging and cerebrospinal fluid data were analysed for all patients who presented with symptoms suspicious for MS at the university based MS outpatient clinic between 2006 and 2010 (n = 165). RESULTS: Follow-up was available for 131 patients. During the mean follow-up period of 2 years, 19% of patients developed CDMS whereas 64% of the patients fulfilling McDonald 2010 criteria did not convert to CDMS. CONCLUSION: The low clinical conversion rate indicates that the new diagnostic criteria may increase the incidence of MS cases with a less active disease course.

[Telemonitoring and pulmonary artery pressure-guided treatment of heart failure]. / Telemonitoring und Pulmonalisdruck-geführte Therapie der Herzinsuffizienz.

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.

Observation of a Charge Density Wave Incommensuration Near the Superconducting Dome in Cu_{x}TiSe_{2}.

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.

[The Therapeutic Dilemma in Treatment of Intracranial Infectious Aneurysm in Patients with Infective Endocarditis: Proposal for a Patient-Centered, Interdisciplinary Treatment Concept]. / Das infektiöse Pseudoaneurysma - eine seltene Komplikation bei Patienten mit septischem Krankheitsbild: aktuelle Datenlage und Vorschlag eines diagnostischen und therapeutischen Algorithmus.

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.

[Riociguat: stimulator of soluble guanylate-cyclase. New mode of action for the treatment of pulmonary arterial and non operable chronic thromboembolic pulmonary hypertension]. / Riociguat: Stimulation der löslichen Guanylatzyklase. Neuer Wirkmechanismus zur Behandlung der pulmonal-arteriellen und der nicht operablen chronisch thromboembolischen pulmonalen Hypertonie.

Riociguat is the first clinically available soluble Guanylate-cyclase stimulator (sGC) and representative of a completely new class of drugs. Riociguat is approved for pulmonary arterial hypertension (PAH) and non-operable or recurrent/persistent chronic thromboembolic pulmonary hypertension (CTEPH). Moreover, Riociguat is currently under investigation for a wider spectrum of diseases. This article focusses on its mode of action and clinical trial data. Finally, based on these data, the status of approval, as well as the costs a proposal is given how Riociguat can be integrated in the current treatment of PAH and CTEPH.

Echocardiographic screening for pulmonary arterial hypertension in HIV-positive patients.

Human immunodeficiency virus (HIV) infection is associated with an increased risk for pulmonary arterial hypertension (PAH). Upon the screening of 220 asymptomatic HIV-positive individuals by echocardiography, we detected and confirmed HIV-associated PAH in 0.45 % of cases. Mild elevations of systolic pulmonary arterial pressure most probably owing to left ventricular diastolic dysfunction were found in 7.7 % of cases, without progress after 2 years. We suggest that the screening of asymptomatic HIV-positive patients for PAH should not be performed.

Unconventional superconductivity in Ba(0.6)K(0.4)Fe2As2 from inelastic neutron scattering.

A new family of superconductors containing layers of iron arsenide has attracted considerable interest because of their high transition temperatures (T(c)), some of which are >50 K, and because of similarities with the high-T(c) copper oxide superconductors. In both the iron arsenides and the copper oxides, superconductivity arises when an antiferromagnetically ordered phase has been suppressed by chemical doping. A universal feature of the copper oxide superconductors is the existence of a resonant magnetic excitation, localized in both energy and wavevector, within the superconducting phase. This resonance, which has also been observed in several heavy-fermion superconductors, is predicted to occur when the sign of the superconducting energy gap takes opposite values on different parts of the Fermi surface, an unusual gap symmetry which implies that the electron pairing interaction is repulsive at short range. Angle-resolved photoelectron spectroscopy shows no evidence of gap anisotropy in the iron arsenides, but such measurements are insensitive to the phase of the gap on separate parts of the Fermi surface. Here we report inelastic neutron scattering observations of a magnetic resonance below T(c) in Ba(0.6)K(0.4)Fe(2)As(2), a phase-sensitive measurement demonstrating that the superconducting energy gap has unconventional symmetry in the iron arsenide superconductors.

The effects of short-term fish oil supplementation on pulmonary function and airway inflammation following a high-fat meal.

INTRODUCTION: Many environmental and dietary influences can cause immune cells to produce biological mediators that increase airway inflammation. A high-fat meal (HFM) is one stimulus that increases airway inflammation in healthy individuals. Supplementation with omega-3 fatty acids can reduce inflammation systemically and may be beneficial to the airways. PURPOSE: To determine if omega-3 fatty acid supplementation via fish oil would mitigate the airway inflammatory response induced by a single HFM. METHODS: Seventeen non-asthmatic men (22 ± 2 years.) were supplemented with 3,000 mg × day(-1) fish oil or a placebo for 3 weeks. Fractional exhaled nitric oxide (FENO; a marker of airway inflammation), impulse oscillometry (a measure of respiratory impedance), pulmonary function, and triglycerides were measured prior to and 2 h following a HFM. RESULTS: Following a HFM, triglycerides increased in both fish oil and placebo groups compared to pre-HFM (~59 and ~49 %, respectively, p < 0.05). The percent increase in FENO was greater in the placebo group compared to the fish oil group (25.7 ± 16.7 vs. -1.99 ± 10.5 %, respectively, p < 0.05). A significant correlation was observed between blood triglycerides and FENO in the placebo group (r = 0.61; p < 0.05), but not the fish oil group (p = 0.21). CONCLUSION: A single HFM increases airway inflammation and omega-3 fatty acid supplementation via fish oil protects against HFM associated changes in airway health.

[Cor pulmonale and pulmonary hypertension. Update after the world conference in Nice]. / Cor pulmonale und pulmonale Hypertonie. Update nach der Weltkonferenz in Nizza.

Pulmonary hypertension (PH) is a common phenomenon which may occur as a consequence of various diseases (e.g. heart failure, chronic lung diseases and pulmonary embolism), as a distinct disease of the small pulmonary arterioles or a combination of both. Independent from the origin, PH has an important impact on patient symptoms and prognosis. Establishment of an exact diagnosis and classification as well as an understanding of the hemodynamic interrelationships provide the basis for often challenging treatment decisions. Recently, the fifth World Symposium on PH took place in Nice, France, where important standards and definitions were specified. The most relevant results including the rating of novel treatment options are summarized in this article.

Evolution of magnetic surfboards and spin glass behavior in (Fe1-pGap)2TiO5.

The unusual anisotropy of the spin glass (SG) transition in the pseudobrookite system Fe2TiO5has been interpreted as arising from an induced, van der Waals-like, interaction among magnetic clusters. Here we present susceptibility (χ) and specific heat data (C) for Fe2TiO5diluted with non-magnetic Ga, (Fe1-pGap)2TiO5, for disorder parameterp= 0, 0.11, and 0.42, and elastic neutron scattering data forp= 0.20. A uniform suppression ofTgis observed upon increasingp, along with a value ofχTgthat increases asTgdecreases, i.e.dχ(Tg)/dTg<0We also observeCT∝T2in the low temperature limit. The observed behavior places (Fe1-pGap)2TiO5in the category of a strongly geometrically frustrated SG.

High contrast x-ray speckle from atomic-scale order in liquids and glasses.

The availability of ultrafast pulses of coherent hard x rays from the Linac Coherent Light Source opens new opportunities for studies of atomic-scale dynamics in amorphous materials. Here, we show that single ultrafast coherent x-ray pulses can be used to observe the speckle contrast in the high-angle diffraction from liquid Ga and glassy Ni(2)Pd(2)P and B(2)O(3). We determine the thresholds above which the x-ray pulses disturb the atomic arrangements. Furthermore, high contrast speckle is observed in scattering patterns from the glasses integrated over many pulses, demonstrating that the source and optics are sufficiently stable for x-ray photon correlation spectroscopy studies of dynamics over a wide range of time scales.