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Cardiologists performing coronary angiography (CA) and percutaneous coronary intervention (PCI) are at risk of health problems related to chronic occupational radiation exposure. Unlike during CA and PCI, physician radiation exposure during right heart catheterization (RHC) and endomyocardial biopsy (EMB) has not been adequately studied. The objective of this study was to assess physicians' radiation doses during RHC with and without EMB and compare them to those of CA and PCI.Procedural head-level physician radiation doses were collected by real-time dosimeters. Radiation-dose metrics (fluoroscopy time, air kerma [AK] and dose area product [DAP]), and physician-level radiation doses were compared among RHC, RHC with EMB, CA, and PCI.Included in the study were 351 cardiac catheterization procedures. Of these, 36 (10.3%) were RHC, 42 (12%) RHC with EMB, 156 (44.4%) CA, and 117 (33.3%) PCI. RHC with EMB and CA had similar fluoroscopy time. AK and DAP were progressively higher for RHC, RHC with EMB, CA, and PCI. Head-level physician radiation doses were similar for RHC with EMB vs CA (P = 0.07). When physicians' radiation doses were normalized to DAP, RHC and RHC with EMB had the highest doses.Physicians' head-level radiation doses during RHC with EMB were similar to those of CA. After normalizing to DAP, RHC and RHC with EMB were associated with significantly higher physician radiation doses than CA or PCI. These observations suggest that additional protective measures should be undertaken to decrease physicians' radiation exposure during RHC and, in particular, RHC with EMB.

Historically, patients with restrictive (RCM) and hypertrophic cardiomyopathy (HCM) experienced longer wait-times for heart transplant (HT) and increased waitlist mortality. Recently, a new HT allocation system was implemented in the United States. We sought to determine the impact of the new HT system on RCM/HCM patients. Adult patients with RCM/HCM listed for HT between November 2015 and September 2019 were identified from the UNOS database. Patients were stratified into two groups: old system and new system. We identified 872 patients who met inclusion criteria. Of these, 608 and 264 were classified in the old and new system groups, respectively. The time in the waitlist was shorter (25 vs. 54 days, P

Background: Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. Methods: In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II–III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2–4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. Findings: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (−36 mm Hg, 95% CI −43·2 to −28·1; p2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB −1·8, −2·4 to −1·2; p

Extensive deployment of solar energy conversion systems requires the development of materials and technologies which go beyond utility-scale Si photovoltaics (PV) solar cells. For instance, thin-film technologies (currently dominated by CIGS and CdTe) are particularly suited to flexible and building integrated PV, a sector predicted to grow to global market revenues of over $5bn by 2025.1 In the lower TRL scale, monolithic integrated III-V tandem devices have pushed the efficiency of photo-electrochemical (PEC) water-splitting to levels which can compete with PV powered electrolysers.2-4 However, PEC systems are yet to show the levels of stability, performance and balance of costs required for technological deployment. As elegantly exposed by Rajeshwar and colleagues,5-6 both fields require exploring the vast space provided by solid-state chemistry in order to identify new families of compound semiconductors with: (i) appropriate band gap for solar energy conversion, (ii) optimal electronic properties featuring high carrier mobility and defect tolerance, (iii) processable by solution-based methods and (iv) composed of Earth abundant and low-cost materials. Defect tolerance is a key descriptor in the search of new solar absorbers, in which Bi3+ and Pb2+ are key cations exhibiting large spin-orbit coupling, dielectric constants and band dispersion.7,8 In a recent study, we have shown that high quality polycrystalline PbI2 thin films exhibit ideal photoelectrode properties towards hydrogen evolution, following the Gartner-limit down to the flat-band potential.9 In this contribution, we will present our recent studies on Bi based absorbers including BiFeO3 and BiI3. BiI3 is prepared by spontaneous gas-phase iodination of Bi2S3 films at 200˚C.10 The films exhibit a high degree of phase purity, p-type conductivity (acceptor density of the order of 1015 cm-3) and a band gap of 1.7 eV. Thin-film devices with the structure Glass/FTO/TiO2/BiI3/F8/Au, where F8 is Poly(9,9-di-n-octylfluorenyl-2,7-diyl), display open-circuit voltage above 600 mV and record power conversion efficiency of 1.2% under AM 1.5G illumination. We have implemented a similar approach to the preparation of high quality BiFeO3 thin films, in which thermolysis of the sulphide precursor is carried out in air. Our early work on devices with the structure graphite/BiFeO3/ZnO/ITO/SLG yielded conversion efficiencies close to 4%, which is among the highest for all-oxide PV systems.11 We shall also contrast the PEC hydrogen generation of BiFeO3 with other poorly understood materials such as BiOCl.12 References: 1- C. Ballif et al. Nat. Energy 2018, 3, 438 2- J.L. Young et al. Nat. Energy 2017, 2, 17028 3- M.M. May et al. Nat. Commun. 2015, 6, 8286 4- E. Verlage et al. Energy Environ. Sci. 2015, 8, 3166 5- K. Rajeshwar et al. J. Electrochem. Soc. 2018, 165, H3192 6- K. Rajeshwar et al. J. Appl. Electrochem. 2007, 37, 765 7- A.M. Ganose et al. Chem. Commun. 2017, 53, 20 8- R.E. Brandt et al., MRS Commun. 2015, 5, 265 9- D. Tiwari, Electrochim. Acta 2018, 254, 223 10- D. Tiwari and D.J. Fermin, ACS Energy Lett. 2018, 3, 1882 11- D. Tiwari et al. J. Phys. Chem. C 2015, 119, 5872 12- J. Stephenson, et al. J. Electroanal. Chem. 2018, 819, 171

The direct visualization of local events leading to the formation of a critical nucleus remains as one of the most formidable challenges in electrodeposition. Recently, state-of-the-art video-rate scanning tunnelling microscopy has been able to follow lateral growth of Bi deposits with exquisite atomic resolution [1]. However, strong local potential bias between tip and substrate often leads to ‘shielding effects’, significantly decreasing local nucleation rates. Substrate-tip interactions in conventional atomic force microscopy also have a strong effect in local nucleation rate. In this contribution, we shall demonstrate a new approach to monitor individual nucleation events based on tracking local perturbations of hydration shells employing high-speed lateral molecular force microscopy (HS-LMFM). A unique optical feedback mechanism lies at the center of the operating mode of HS-LMFM [2,3]. Under this configuration, the position of a vertically oriented probe (VOP) is tracked by measuring the scattering of the evanescent wave of a laser impinging under total internal reflection from the back of an optically transparent electrode. As the tip approaches the surface oscillating close to its resonant frequency, the oscillation frequency is affected by the visco-elastic properties of the various hydration layers. Changes in the VOP oscillations are optically detected by the scattering evanescent field. This approach enables monitoring interaction with individual hydration layers simultaneously with, but independent of, the optical feedback. In these experiments, the tip is positioned at a distance in which shear force interactions with hydration layers of an In-doped SnO2 electrode (approximately 2.9 nm roughness level) become negligible [4]. As nucleation events are triggered, the hydration layers around individual nuclei move into a detectable range of the VOP, leading to changes in the oscillation frequency. Shear force maps uncover a highly dynamic landscape prior to the formation of stable nucleus. At constant potential, the stochastic formation and dissolution of nuclei can be observed in the sub-second time scale. The growth of a stable nucleus is also followed in real-time, illustrating the potential of this technique for probing complex phase formation phenomena at electrode surfaces. References Matsushima, H. et al. Faraday Discuss. 193, 171-185 (2016). Fletcher, J. M. et al. Science 340, 595-599 (2013). Antognozzi, M. et al. Nat. Phys. 12, 731-735 (2016). Harniman, R.L. et al. Nat. Commun. 8, 971 (2017)

PbI2 has become a highly prominent material in the field of photovoltaics as the key precursor in the fabrication of organo-halide perovskites films [1]. Despite intensive research in this area, the role of unconverted PbI2 in perovskite cells remains controversial. In fact, very little is known about the behaviour of PbI2 as a photocathode. In this contribution, we examine the photoelectrochemical properties of high quality PbI2 thin films obtained by gas phase anion replacement [2]. The preparation of PbI2 films is initiated by growing a thin PbS film on F:SnO2 electrodes, followed by spontaneous gas phase iodination at 200 ˚C. The structure and optical properties of the thin films were investigated by XRD, SEM, Raman Spectroscopy, diffuse reflectance and room temperature photoluminescence. The structural and spectroscopic information, supported by DFT calculations (PBESOL functionals), demonstrated the formation of the 2H- phase of PbI2 with a high degree of purity and a band gap of 2.4 eV. Electrochemical impedance spectroscopy in KI containing solutions showed a clear p-type behaviour with a flat band potential located 0.175 V vs Ag/AgCl and an effective majority carrier density of 1.6×1015 cm-3. Photoelectrochemical studies in Ar-saturated KI solutions were characterized by a nearly ideal semiconductor-electrolyte junction at low illumination levels. Incident-photon-to-current efficiency exhibits values close to 50%, which can be quantitatively rationalized in terms of reflection losses, the width of the space charge region and a minority carrier diffusion length of 80 nm. The remarkable feature of this photocathode is the absence of surface recombination even at potentials close to the flat band value. The efficient hydrogen photogeneration is achieved at neutral pH and in the absence of co-catalysts. We shall briefly discuss the origin of the nearly ideal semiconductor-electrolyte junction behaviour and potential routes for stabilising the PbI2 surface for solar fuel applications. References Yang and J. You, Nature 544 (2017) 155 Tiwari and D.J. Fermin, Electrochim. Acta 254 (2017) 223

Complex transition metal oxides such as perovskites have been extensively investigated in the context of oxygen electrocatalysis.1,2 These materials represent a vast family of compounds with electronic properties sharply dependent on their composition, crystal phase and oxygen content. Consequently, the establishment of structure-activity relationships is of paramount importance in the search of highly active and chemically stable electrocatalysts for alkaline fuel cells. Indeed, the strongly correlated nature of electrons in these materials, as opposed to metallic phases, introduces a high degree of complexity for material screening from first-principle calculations. We have recently examined a range of lanthanide perovskites (LaBO3, with B: Co, Fe, Cr, Mn and Ni) synthesised by a versatile synthetic method capable of generating nanoparticles with a high degree of phase purity.3 We have shown that Mn based oxides show over two orders of magnitude higher activity than any other perovskite towards the 4-electron oxygen reduction reaction (ORR);3,4,5 a difference significantly larger than recognised in previous studies.2,6 In this contribution, we will investigate the origin of the exceptional activity of Mn based perovskites. Our key hypothesis centres around the fact that Mn sites undergo changes in their redox state at potentials close to the formal ORR potential. These redox transitions are key in the oxygen bond breaking step and the overall reactivity of the material. Our studies are underpinned by detailed analysis of the bulk and surface structure employing X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and in-operando X-ray absorption spectroscopy (XAS). We will also show that the intrinsic activity of these materials can be strongly affected by the nature of the A-site7 and the temperature of oxide phase formation. References: 1- A. Grimaud et al. Nat. Mater. 2016, 15, 121 2- J. Suntivich et al. Nat. Chem. 2011, 3, 647 3- V. Celorrio et al. ChemElectroChem 2016, 3, 283 4- V. Celorrio et al. Catal. Sci. & Technol. 2016, 6, 7231 5- V. Celorrio et al. J. Phys. Chem. C. 2016, 120, 22291 6- K.A. Stoerzinger, ACS Catalysis 2015, 5, 6021 7- V. Celorrio, MRS Commun. 2017, DOI: 10.1557/mrc.2017.22

It is well established that thin metal layers on a foreign support can exhibit very distinctive electrocatalytic activity with respect to bulk electrodes. In the case of d­-metals, changes in reactivity can be rationalised in terms of the so-called ligand or strain (also known as geometric) effects. Although is commoly argued that ligand effects are rather short range (sub-monolayer to few atomic layers), it is notoriusly difficult to experimentally differentiate the contributions from these two phenomena. In this contribution, we shall explore ligand and strain effects on the electrocatalytic properties of Au-Pd core-shell nanoparticles towards CO2 reduction to fuels. The electrochemical properties and product generation are probed by off-line 1H NMR, differential electrochemical mass spectrometry (DEMS), on-line Mass spectrometry (OLEMS) and in-situ FTIR. Thin Pd shells were grown onto 20 nm Au nanoparticles employing a colloidal synthesis method at low temperatures, generating continuous shells with tuneable mean thickness between 1.3±0.1 (CS1) and 9.9±1.1 nm (CS10). Selected area electron diffraction patterns revealed that the effective Pd strain decreases from 3.5 to less than 1% in this thickness range, which is consistent with strain relaxtion mechanisms at Au {111} surfaces. DEMS was used to calculate the faradaic efficiency associated with the CO2 reduction vs hydrogen evolution at the core-shell nanostructures supported on a porous carbon layer. The data show that over 90% of the faradaic charge in the range between 0.0 to -0.5 V vs RHE is consumed in CO2 conversion at CS1 nanoparticles, as opposed to approximately 40% in the case of CS10. The analysis of the electrolyte solution employing 1H NMR revealed the formation of HCOO- only in the case of CS10 over a narrow potential range centred at -0.4 V, with faradaic efficiencies close to 30%. Furthermore, CH4 and C2H6 were also detected using OLEMS at potentials as negative as -0.7 V at the CS10 nanoparticles. No products in solution were detected In the case of CS1, indicating that CO is the main product generated over the entire potential range. The contrast in reaction pathway and electrocatalytic performance are rationalised in terms of the CO affinity to the Pd nanoshells. To probe this, in-situ FTIR studies were performed revealing that the potential dependence of the adsorbed C-O stretching band (stark slope) is significantly weaker on CS1 in comparison to CS10. Furthermore, the effective CO coverage increases with increasing Pd thickness, reaching values reported for polycrystalline bulk Pd electrodes in the case of CS10. These results show that CO has a significantly weaker binding to strain Pd shells (CS1). Finally DFT calculations are used to estimate the contributions of the so-called ligand and strain effects on the local density of states of the Pd d-band. The calculations strongly suggest that the key parameters contributing to the change in mechanism is the effective lattice strain.

Transition metal oxides such as perovskites (ABO3) are becoming an important class of materials in the context of oxygen electrocatalysis for alkaline fuel cells and metal-air batteries.1,2 Although these materials have been extensively investigated in the field of solid oxide fuel cells, their properties as oxygen electrocatalysts at room temperature are far from being fully rationalised. Establishing structure-activity relationships based on the electronic structure of the B-site, widely recognised as the main active site, is one of the key challenge in this field. Such information is extremely important towards designing catalysts with optimal B-site orbital occupancy, coordination number and metal-oxygen bond length. In a recent study, we have shown that LaMnO3 exhibits over two orders of magnitude higher activity towards the ORR than other lanthanide perovskites (e.g. Co, Fe, Cr and Ni).3 Our analysis show that the origin of this high activity is linked to changes in the redox state at the Mn sites at potentials close to the formal ORR potential, leading to an increase in electron population at the key active site. In this contribution, we shall focus on the structure-activity relationship of a family of LaxCa1-xMnO3 nanoparticles, assessing their activity as a function of the Mn-valency. We will provide a detailed analysis of the bulk and surface structure employing X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and X-ray absorption near edge spectroscopy (XANES). Studies employing rotating ring-disc electrodes of the nanoparticles supported on mesoporous carbon films show that their activity towards the ORR are among the highest reported for transition metal oxides.4 We finally establish that the mean ORR activity of surface Mn sites increases as the Mn valency decreases.5 These studies highlight the need for independent assessment of key aspects such as the extent of A-site surface segregation and average Mn valency in order to establish consistent structure-activity relationships. References: 1- A. Grimaud et al. Nat. Mater. 2016, 15, 121 2- J. Suntivich et al. Nat. Chem. 2011, 3, 647 3- V. Celorrio et al. ChemElectroChem 2016, 3, 283 4- K.A. Stoerzinger, ACS Catalysis 2015, 5, 6021 5- V. Celorrio et al. Catal. Sci. & Technol. 2016, 6, 7231

Background— We report the first comprehensive analysis of gene expression differences by sex and age in left ventricular samples from 102 patients with dilated cardiomyopathy. Methods and Results— Gene expression data (HG-U133A gene chip, Affymetrix) were analyzed from 30 females and 72 males from 3 separate centers. More than 1800 genes displayed sexual dimorphism in the heart (adjusted P value 140 genes were differentially expressed in the 55 years age group. These genes were highly represented in gene ontology pathways involved in DNA damage. In contrast, zero genes in the male cohort 55 years age group. Conclusions— Gene expression in dilated cardiomyopathy displayed evidence of sexual dimorphism similar to other somatic tissues and age dimorphism within the female cohort.

We screened a compendium of gene profiles from 19 paired human heart samples harvested at the time of implant and explant of a left ventricular assist device (LVAD) for novel genes regulating the Ras/MEK/ERK cascade. From this analysis we identified Sprouty1, an evolutionally conserved gene that acts as an intrinsic inhibitor of the Ras/MEK/ERK pathway. Sprouty1 mRNA and protein were significantly upregulated in the heart in response to mechanical unloading with a LVAD. The upregulation of Sprouty1 in the heart following mechanical unloading was accompanied by a significant decrease in phosphorylated ERK1/2. Gain of function experiments demonstrated that upregulation of Sprouty1 in isolated cardiac myocytes led to a significant decrease and altered kinetics of ERK1/2 phosphorylation. Immunohistochemistry of human hearts revealed that Sprouty1 was also expressed in the microvasculature. Upregulation of Sprouty1 in endothelial cells led to a significant decrease in VEGF-induced endothelial cell proliferation. To our knowledge, these findings are the first to define Sprouty expression in the heart and suggest that Sprouty1 may serve as an intrinsic mediator governing ventricular remodeling through a coordinated coupling of both myocyte and vascular alterations in response to mechanical load.

Mechanical unloading of the heart with a left ventricular assist device (LVAD) significantly decreases mortality in patients with heart failure. Moreover, it provides a human model to define the critical regulatory genes governing myocardial remodeling in response to significant reductions in wall stress. Statistical analysis of a gene expression library of 19 paired human heart samples harvested at the time of LVAD implant and again at explant revealed a set of 22 genes that were downregulated and 85 genes that were upregulated in response to mechanical unloading with a false discovery rate of less than 1%. The analysis revealed a high percentage of genes involved in the regulation of vascular networks including neuropilin-1 (a VEGF receptor), FGF9, Sprouty1, stromal-derived factor 1, and endomucin. Taken together these findings suggest that mechanical unloading alters the regulation of vascular organization and migration in the heart. In addition to vascular signaling networks, GATA-4 binding protein, a critical mediator of myocyte hypertrophy, was significantly downregulated following mechanical unloading. In summary, these findings may have important implications for defining the role of mechanical stretch and load on autocrine/paracrine signals directing vascular organization in the failing human heart and the role of GATA-4 in orchestrating reverse myocardial remodeling. This unbiased gene discovery approach in paired human heart samples has the potential to provide critical clues to the next generation of therapeutic treatments aimed at heart failure.

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