New PV system concept : inductive power transfer for PV modules

The proposed new PV system concept is based on several AC modules that are connected in series using inductive power transfer. These modules include a cell matrix that is connected to a module integrated DC/AC inverter. The high frequency AC current flows through the primary side planar coil generating a magnetic flux. Outside of the PV module, there is a clamp including ferromagnetic material for the magnetic circuit that caries the magnetic flux to the secondary winding. The magnetic flux induces an AC current in the secondary winding, which is formed by the common cable. An AC/AC converter is placed at the end of the PV module strings to generate the 50 Hz and to connect the PV power plant to the electricity grid. This new PV system concept is a fundamentally new approach of the electricity transmission in the field of PV system technology. It is not restricted to the replacement or optimisation of an individual system component, but it requires the continuing development of the PV module construction and the contactless connection technology to the common cable. The proposed inductive power transfer per each PV module opens up a complete new field for the PV system technology

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT02866838

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial

BACKGROUND: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (P$_{interaction}$=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH

Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency

Multi-layered omics approaches can help define relationships between genetic factors, biochemical processes and phenotypes thus extending research of inherited diseases beyond identifying their monogenic cause 1. We implemented a multi-layered omics approach for the inherited metabolic disorder methylmalonic aciduria (MMA). We performed whole genome sequencing, transcriptomic sequencing, and mass spectrometry-based proteotyping from matched primary fibroblast samples of 230 individuals (210 affected, 20 controls) and related the molecular data to 105 phenotypic features. Integrative analysis identified a molecular diagnosis for 84% (177/210) of affected individuals, the majority (148) of whom had pathogenic variants in methylmalonyl-CoA mutase (MMUT). Untargeted analysis of all three omics layers revealed dysregulation of the TCA cycle and surrounding metabolic pathways, a finding that was further corroborated by multi-organ metabolomics of a hemizygous Mmut mouse model. Integration of phenotypic disease severity indicated downregulation of oxoglutarate dehydrogenase and upregulation of glutamate dehydrogenase, two proteins involved in glutamine anaplerosis of the TCA cycle. The relevance of disturbances in this pathway was supported by metabolomics and isotope tracing studies which showed decreased glutamine-derived anaplerosis in MMA. We further identified MMUT to physically interact with both, oxoglutarate dehydrogenase complex components and glutamate dehydrogenase providing evidence for a multi-protein metabolon that orchestrates TCA cycle anaplerosis. This study emphasizes the utility of a multi-modal omics approach to investigate metabolic diseases and highlights glutamine anaplerosis as a potential therapeutic intervention point in MMA. Take home message Combination of integrative multi-omics technologies with clinical and biochemical features leads to an increased diagnostic rate compared to genome sequencing alone and identifies anaplerotic rewiring as a targetable feature of the rare inborn error of metabolism methylmalonic aciduria

Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology.

80These guidelines focus on valvular heart disease in adults and adolescents, are oriented towards management, and will not deal with endocarditis and congenital valve diseases in adults and adolescents, since recent guidelines have been produced by the ESC on these topics. Although valvular heart disease is less common in industrialized countries than coronary disease, heart failure, or hypertension, guidelines are needed in this field for several reasons: valvular heart disease is common and often requires intervention; substantial advances have been made in the understanding of its pathophysiology; the patient population has changed with a continuous decline of acute rheumatic fever and an increased incidence of degenerative valvular diseases in industrialized countries. The incidence of endocarditis remains stable and other causes of valve disease are rare. Because of the predominance of degenerative valve disease, the two most frequent valve diseases are now calcific aortic stenosis and mitral regurgitation. Aortic regurgitation and mitral stenosis have become less common. Diagnosis is now dominated by echocardiography, which has become the standard to evaluate valve structure and function. Treatment has not only developed through the continuing progress in prosthetic valve technology, but has also been reoriented by the development of conservative surgical approaches and the introduction of percutaneous interventional techniques.openopenVahanian, A; Baumgartner, ; H, ; Bax, ; J, ; Butchart, ; E, ; Dion, ; R, ; Filippatos, ; G, ; Flachskampf, ; F, ; Hall, ; R, ; Iung, ; B, ; Kasprzak, ; J, ; Nataf, ; P, ; Tornos, ; P, ; Torracca, ; L, ; Wenink, ; A, ; Silvia, ; Priori, G.; Blanc, Jean-Jacques; Andrzej, ; Budaj, ; John, ; Camm, ; Veronica, ; Dean, ; Jaap, ; Deckers, ; Kenneth, ; Dickstein, ; John, ; Lekakis, ; Keith, ; Mcgregor, ; Marco, ; Metra, ; João, ; Morais, ; Ady, ; Osterspey, ; Juan, ; Tamargo, ; Luis, José; Zamorano, ; Annalisa, ; Angelini, ; Manuel, ; Antunes, ; Angel, Miguel; Fernandez, Garcia; Christa, ; Gohlke-Baerwolf, ; Gilbert, ; Habib, ; John, ; Mcmurray, ; Catherine, ; Otto, ; Luc, ; Pierard, ; Josè, ; Pomar, L.; Bernard, ; Prendergast, ; Raphael, ; Rosenhek, ; Sousa, Miguel; Uva, ; Juan, ; Tamargo,Vahanian, A; Baumgartner, ; H, ; Bax, ; J, ; Butchart, ; E, ; Dion, ; R, ; Filippatos, ; G, ; Flachskampf, ; F, ; Hall, ; R, ; Iung, ; B, ; Kasprzak, ; J, ; Nataf, ; P, ; Tornos, ; P, ; Torracca, ; L, ; Wenink, ; A, ; Silvia, ; Priori, G.; Blanc, Jean Jacques; Andrzej, ; Budaj, ; John, ; Camm, ; Veronica, ; Dean, ; Jaap, ; Deckers, ; Kenneth, ; Dickstein, ; John, ; Lekakis, ; Keith, ; Mcgregor, ; Marco, ; Metra, Marco; João, ; Morais, ; Ady, ; Osterspey, ; Juan, ; Tamargo, ; Luis, José; Zamorano, ; Annalisa, ; Angelini, ; Manuel, ; Antunes, ; Angel, Miguel; Fernandez, Garcia; Christa, ; Gohlke, Baerwolf; Gilbert, ; Habib, ; John, ; Mcmurray, ; Catherine, ; Otto, ; Luc, ; Pierard, ; Josè, ; Pomar, L.; Bernard, ; Prendergast, ; Raphael, ; Rosenhek, ; Sousa, Miguel; Uva, ; Juan, ; Tamargo

Retention of progenitor cell phenotype in otospheres from guinea pig and mouse cochlea

Abstract\ud \ud Background\ud Culturing otospheres from dissociated organ of Corti is an appropriate starting point aiming at the development of cell therapy for hair cell loss. Although guinea pigs have been widely used as an excellent experimental model for studying the biology of the inner ear, the mouse cochlea has been more suitable for yielding otospheres in vitro. The aim of this study was to compare conditions and outcomes of otosphere suspension cultures from dissociated organ of Corti of either mouse or guinea pig at postnatal day three (P3), and to evaluate the guinea pig as a potential cochlea donor for preclinical cell therapy.\ud \ud \ud Methods\ud Organs of Corti were surgically isolated from P3 guinea pig or mouse cochlea, dissociated and cultivated under non-adherent conditions. Cultures were maintained in serum-free DMEM:F12 medium, supplemented with epidermal growth factor (EGF) plus either basic fibroblast growth factor (bFGF) or transforming growth factor alpha (TGFα). Immunofluorescence assays were conducted for phenotype characterization.\ud \ud \ud Results\ud The TGFα group presented a number of spheres significantly higher than the bFGF group. Although mouse cultures yielded more cells per sphere than guinea pig cultures, sox2 and nestin distributed similarly in otosphere cells from both organisms. We present evidence that otospheres retain properties of inner ear progenitor cells such as self-renewal, proliferation, and differentiation into hair cells or supporting cells.\ud \ud \ud Conclusions\ud Dissociated guinea pig cochlea produced otospheres in vitro, expressing sox2 and nestin similarly to mouse otospheres. Our data is supporting evidence for the presence of inner ear progenitor cells in the postnatal guinea pig. However, there is limited viability for these cells in neonatal guinea pig cochlea when compared to the differentiation potential observed for the mouse organ of Corti at the same developmental stage

Discovery of X-ray polarization angle rotation in active galaxy Mrk 421

The magnetic field conditions in astrophysical relativistic jets can be probed by multiwavelength polarimetry, which has been recently extended to X-rays. For example, one can track how the magnetic field changes in the flow of the radiating particles by observing rotations of the electric vector position angle $\Psi$. Here we report the discovery of a $\Psi_{\mathrm x}$ rotation in the X-ray band in the blazar Mrk 421 at an average flux state. Across the 5 days of Imaging X-ray Polarimetry Explorer (IXPE) observations of 4-6 and 7-9 June 2022, $\Psi_{\mathrm x}$ rotated in total by $\geq360^\circ$. Over the two respective date ranges, we find constant, within uncertainties, rotation rates ($80 \pm 9$ and $91 \pm 8 ^\circ/\rm day$) and polarization degrees ($\Pi_{\mathrm x}=10\%\pm1\%$). Simulations of a random walk of the polarization vector indicate that it is unlikely that such rotation(s) are produced by a stochastic process. The X-ray emitting site does not completely overlap the radio/infrared/optical emission sites, as no similar rotation of $\Psi$ was observed in quasi-simultaneous data at longer wavelengths. We propose that the observed rotation was caused by a helical magnetic structure in the jet, illuminated in the X-rays by a localized shock propagating along this helix. The optically emitting region likely lies in a sheath surrounding an inner spine where the X-ray radiation is released

Magnetic Field Properties inside the Jet of Mrk 421: Multiwavelength Polarimetry Including the Imaging X-ray Polarimetry Explorer

We conducted a polarimetry campaign from radio to X-ray wavelengths of the high-synchrotron-peak (HSP) blazar Mrk 421, including Imaging X-ray Polarimetry Explorer (IXPE) measurements on 2022 December 6-8. We detected X-ray polarization of Mrk 421 with a degree of $\Pi_{\rm X}$=14$\pm$1$\%$ and an electric-vector position angle $\psi_{\rm X}$=107$\pm$3$^{\circ}$ in the 2-8 keV band. From the time variability analysis, we find a significant episodic variation in $\psi_{\rm X}$. During 7 months from the first IXPE pointing of Mrk 421 in 2022 May, $\psi_{\rm X}$ varied across the range of 0$^{\circ}$ to 180$^{\circ}$, while $\Pi_{\rm X}$ maintained similar values within $\sim$10-15$\%$. Furthermore, a swing in $\psi_{\rm X}$ in 2022 June was accompanied by simultaneous spectral variations. The results of the multiwavelength polarimetry show that the X-ray polarization degree was generally $\sim$2-3 times greater than that at longer wavelengths, while the polarization angle fluctuated. Additionally, based on radio, infrared, and optical polarimetry, we find that rotation of $\psi$ occurred in the opposite direction with respect to the rotation of $\psi_{\rm X}$ over longer timescales at similar epochs. The polarization behavior observed across multiple wavelengths is consistent with previous IXPE findings for HSP blazars. This result favors the energy-stratified shock model developed to explain variable emission in relativistic jets. The accompanying spectral variation during the $\psi_{\rm X}$ rotation can be explained by a fluctuation in the physical conditions, e.g., in the energy distribution of relativistic electrons. The opposite rotation direction of $\psi$ between the X-ray and longer-wavelength polarization accentuates the conclusion that the X-ray emitting region is spatially separated from that at longer wavelengths.Comment: 17 pages, 13 figures, 4 tables; Accepted for publication in A&