The prognostic value of DLCO and pulmonary blood flow in patients with pulmonary hypertension

Background Cardiac output is a prognostic marker in patients with pulmonary hypertension. Pulmonary blood flow as a surrogate for cardiac output can be measured non-invasively by inert gas rebreathing. We hypothesized that pulmonary blood flow can predict outcome in patients with pulmonary hypertension. Methods From January 2009 to January 2012, we measured pulmonary blood flow by inert gas rebreathing in outpatients with pulmonary hypertension. Patients with pulmonary hypertension confirmed by right heart catheterization and a valid inert gas rebreathing maneuver were followed until January 2016. The investigated outcome was all-cause mortality. Results We included 259 patients (mean age 65 +/- 13 years, 53% female) with pulmonary hypertension and classified into groups 1 (n = 103), 2 (n = 26), 3 (n = 80), and 4 (n = 50) according to the current pulmonary hypertension classification system. The median time between pulmonary hypertension diagnosis and inert gas rebreathing was 9 (IQR 0; 36) months. During a median follow-up time of 51 (IQR 20; 68) months, 109 patients (42%) died. Parameters significantly associated with survival (in order of decreasing statistical strength) were diffusion capacity of the lung for carbon monoxide (DLCO), 6-minute walk distance (6-MWD), age, NTpro-BNP, WHO functional class, group 3 pulmonary hypertension, and tricuspid annular plane systolic excursion (TAPSE), while baseline hemodynamics and pulmonary blood flow were not. In multivariable Cox regression analysis, DLCO, age, 6-MWD, and TAPSE remained significant and independent predictors of the outcome. DLCO as the strongest parameter also significantly predicted survival in aetiological subgroups except for group 4. Conclusions DLCO is a strong and independent predictor for survival in patients with pulmonary hypertension of different aetiologies, while pulmonary blood flow measured by inert gas rebreathing is not

Rainfall threshold for initiating effective stress decrease and failure in weathered tephra slopes

Rainfall is one of the most important triggers of slope failure. Weathered pyroclastic (tephra) deposits are especially vulnerable to slope failure because they commonly form slopes of high porosity and high clay content. Empirically derived thresholds for the triggering of landslides are commonly based on rainfall conditions and have been widely applied in volcanic soils. However, so far only few researchers utilized pore water pressure in the slope as additional variable for the threshold calibration. Here, we derived a new rainfall threshold for initiating the decrease in effective stress in the slope by analyzing a long-term record of rainfall and piezometer data from a slide-prone coastal area in northern New Zealand that consists of clayey, halloysitic tephra deposits. The level of effective stress decrease increased with rainfall intensity and duration. We observed highest effective stress decrease of up to 36% during rainfall events that triggered landslides in our study area. The effective stress threshold exhibits a satisfactory predictive capability. The probability of correctly predicting a decrease in effective stress is 53%. The effective stress threshold contributes towards the implementation of the decrease in effective stress into rainfall thresholds for the occurrence of landslides

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome

Change of right heart size and function by long-term therapy with riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

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An Optical Atomic Clock Based on a Highly Charged Ion

Optical atomic clocks are the most accurate measurement devices ever constructed and have found many applications in fundamental science and technology. The use of highly charged ions (HCI) as a new class of references for highest accuracy clocks and precision tests of fundamental physics has long been motivated by their extreme atomic properties and reduced sensitivity to perturbations from external electric and magnetic fields compared to singly charged ions or neutral atoms. Here we present the first realisation of this new class of clocks, based on an optical magnetic-dipole transition in Ar$^{13+}$. Its comprehensively evaluated systematic frequency uncertainty of $2.2\times10^{-17}$ is comparable to that of many optical clocks in operation. From clock comparisons we improve by eight and nine orders of magnitude upon the uncertainties for the absolute transition frequency and isotope shift ($^{40}$Ar vs. $^{36}$Ar), respectively. These measurements allow us to probe the largely unexplored quantum electrodynamic nuclear recoil, presented as part of improved calculations of the isotope shift which reduce the uncertainty of previous theory by a factor of three. This work establishes forbidden optical transitions in HCI as references for cutting-edge optical clocks and future high-sensitivity searches for physics beyond the standard model.Comment: Main: 20 pages, 3 figures. Supplement: 19 pages, 2 figure

Left ventricular support adjustment to aortic valve opening with analysis of exercise capacity

Background LVAD speed adjustment according to a functioning aortic valve has hypothetic advantages but could lead to submaximal support. The consequences of an open aortic valve policy on exercise capacity and hemodynamics have not yet been investigated systematically. Methods Ambulatory patients under LVAD support (INCOR®, Berlin Heart, mean support time 465 ± 257 days, average flow 4.0 ± 0.3 L/min) adjusted to maintain a near normal aortic valve function underwent maximal cardiopulmonary exercise testing (CPET) and right heart catheterization (RHC) at rest and during constant work rate exercise (20 Watt). Results Although patients (n = 8, mean age 45 ± 13 years) were in NYHA class 2, maximum work-load and peak oxygen uptake on CPET were markedly reduced with 69 ± 13 Watts (35% predicted) and 12 ± 2 mL/min/kg (38% predicted), respectively. All patients showed a typical cardiac limitation pattern and severe ventilatory inefficiency with a slope of ventilation to carbon dioxide output of 42 ± 12. On RHC, patients showed an exercise-induced increase of mean pulmonary artery pressure (from 16 ± 2.4 to 27 ± 2.8 mmHg, p < 0.001), pulmonary artery wedge pressure (from 9 ± 3.3 to 17 ± 5.3 mmHg, p = 0.01), and cardiac output (from 4.7 ± 0.5 to 6.2 ± 1.0 L/min, p = 0.008) with a corresponding slight increase of pulmonary vascular resistance (from 117 ± 35.4 to 125 ± 35.1 dyn*sec*cm−5, p = 0.58) and a decrease of mixed venous oxygen saturation (from 58 ± 6 to 32 ± 9%, p < 0.001). Conclusion An open aortic valve strategy leads to impaired exercise capacity and hemodynamics, which is not reflected by NYHA-class. Unknown compensatory mechanisms can be suspected. Further studies comparing higher vs. lower support are needed for optimization of LVAD adjustment strategies

Long-term follow-up and quality of life in patients receiving extracorporeal membrane oxygenation for pulmonary embolism and cardiogenic shock

Background Since 2019, European guidelines recommend considering extracorporeal life support as salvage strategy for the treatment of acute high-risk pulmonary embolism (PE) with circulatory collapse or cardiac arrest. However, data on long-term survival, quality of life (QoL) and cardiopulmonary function after extracorporeal membrane oxygenation (ECMO) are lacking. Methods One hundred and nineteen patients with acute PE and severe cardiogenic shock or in need of mechanical resuscitation (CPR) received venoarterial or venovenous ECMO from 2007 to 2020. Long-term data were obtained from survivors by phone contact and personal interviews. Follow-up included a QoL analysis using the EQ-5D-5L questionnaire, echocardiography, pulmonary function testing and cardiopulmonary exercise testing. Results The majority of patients (n = 80, 67%) were placed on ECMO during or after CPR with returned spontaneous circulation. Overall survival to hospital discharge was 45.4% (54/119). Nine patients died during follow-up. At a median follow-up of 54.5 months (25–73; 56 ± 38 months), 34 patients answered the QoL questionnaire. QoL differed largely and was slightly reduced compared to a German reference population (EQ5D5L index 0.7 ± 0.3 vs. 0.9 ± 0.04; p  < 0.01). 25 patients (73.5%) had no mobility limitations, 22 patients (65%) could handle their activities, while anxiety and depression were expressed by 10 patients (29.4%). Return-to-work status was 33.3% (average working hours: 36.2 ± 12.5 h/per week), 15 (45.4%) had retired from work early. 12 patients (35.3%) expressed limited exercise tolerance and dyspnea. 59% (20/34) received echocardiography and pulmonary function testing, 50% (17/34) cardiopulmonary exercise testing. No relevant impairment of right ventricular function and an only slightly reduced mean peak oxygen uptake (76.3% predicted) were noted. Conclusions Survivors from severe intractable PE in cardiogenic shock or even under CPR with ECMO seem to recover well with acceptable QoL and only minor cardiopulmonary limitations in the long term. To underline these results, further research with larger study cohorts must be obtained

Tuning spontaneous emission through waveguide cavity effects in semiconductor nanowires

The ability to tailor waveguide cavities and couple them with quantum emitters has developed a realm of nanophotonics encompassing, for example, highly efficient single photon generation or the control of giant photon nonlinearities. Opening new grounds by pushing the interaction of the waveguide cavity and integrated emitters further into the deep subwavelength regime, however, has been complicated by nonradiative losses due to the increasing importance of surface defects when decreasing cavity dimensions. Here, we show efficient suppression of nonradiative recombination for thin waveguide cavities using core-shell semiconductor nanowires. We experimentally reveal the advantages of such nanowires, which host mobile emitters, that is, free excitons, in a one-dimensional (1D) waveguide, highlighting the resulting potential for tunable, active, nanophotonic devices. In our experiment, controlling the nanowire waveguide diameter tunes the luminescence lifetime of excitons in the nanowires across 2 orders of magnitude up to 80 ns. At the smallest wire diameters, we show that this luminescence lifetime can be manipulated by engineering the dielectric environment of the nanowires. Exploiting this unique handle on the spontaneous emission of mobile emitters, we demonstrate an all-dielectric spatial control of the mobile emitters along the axis of the 1D nanowire waveguide

Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy

Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

Using a sample of 122 million Upsilon(3S) events recorded with the BaBar detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for the $h_b(1P)$ spin-singlet partner of the P-wave chi_{bJ}(1P) states in the sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We observe an excess of events above background in the distribution of the recoil mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width of the observed signal is consistent with experimental resolution, and its significance is 3.1sigma, including systematic uncertainties. We obtain the value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid Communications