Strain Engineering: Perfecting Freestanding Perovskite Oxide Fabrication.

Freestanding oxide membranes provide a promising path for integrating devices on silicon and flexible platforms. To ensure optimal device performance, these membranes must be of high crystal quality, stoichiometric, and their morphology free from cracks and wrinkles. Often, layers transferred on substrates show wrinkles and cracks due to a lattice relaxation from an epitaxial mismatch. Doping the sacrificial layer of Sr3 Al2 O6 (SAO) with Ca or Ba offers a promising solution to overcome these challenges, yet its effects remain critically underexplored. A systematic study of doping Ca into SAO is presented, optimizing the pulsed laser deposition (PLD) conditions, and adjusting the supporting polymer type and thickness, demonstrating that strain engineering can effectively eliminate these imperfections. Using SrTiO3 as a case study, it is found that Ca1.5 Sr1.5 Al2 O6 offers a near-perfect match and a defect-free freestanding membrane. This approach, using the water-soluble Bax /Cax Sr3-x Al2 O6 family, paves the way for producing high-quality, large freestanding membranes for functional oxide devices.

Inhibition of the acetylcholine-regulated potassium current prevents transient apnea-related atrial arrhythmogenic changes in a porcine model.

BACKGROUND: More than 50% of patients with atrial fibrillation (AF) suffer from sleep disordered breathing (SDB). Obstructive respiratory events contribute to a transient, vagally mediated atrial arrhythmogenic substrate, which is resistant to most available antiarrhythmic drugs. OBJECTIVE: The purpose of this study was to investigate the effect of pharmacologic inhibition of the G-protein-gated acetylcholine-regulated potassium current (IK,ACh) with and without acute autonomic nervous system activation by nicotine in a pig model for obstructive respiratory events. METHODS: In 21 pigs, SDB was simulated by applying an intermittent negative upper airway pressure (INAP). AF inducibility and atrial effective refractory periods (aERPs) were determined before and during INAP by an S1S2 atrial pacing-protocol. Pigs were randomized into 3 groups-group 1: vehicle (n = 4); group 2: XAF-1407 (IK,ACh inhibitor) (n = 7); and group 3: nicotine followed by XAF-1407 (n = 10). RESULTS: In group 1, INAP shortened aERP (ΔaERP -42.6 ms; P = .004) and transiently increased AF inducibility from 0% to 31%. In group 2, XAF-1407 prolonged aERP by 25.2 ms (P = .005) during normal breathing and prevented INAP-induced aERP shortening (ΔaERP -3.6 ms; P = .3) and AF inducibility. In group 3, INAP transiently shortened aERP during nicotine perfusion (ΔaERP -33.6 ms; P = .004) and increased AF inducibility up to 61%, which both were prevented by XAF-1407. CONCLUSION: Simulated obstructive respiratory events transiently shorten aERP and increase AF inducibility, which can be prevented by the IK,ACh-inhibitor XAF-1407. XAF-1407 also prevents these arrhythmogenic changes induced by obstructive respiratory events during nicotine perfusion. Whether IK,ACh channels represent a target for SDB-related AF in humans warrants further study.

Cryogenic multiplexing using selective area grown nanowires.

Bottom-up grown nanomaterials play an integral role in the development of quantum technologies but are often challenging to characterise on large scales. Here, we harness selective area growth of semiconductor nanowires to demonstrate large-scale integrated circuits and characterisation of large numbers of quantum devices. The circuit consisted of 512 quantum devices embedded within multiplexer/demultiplexer pairs, incorporating thousands of interconnected selective area growth nanowires operating under deep cryogenic conditions. Multiplexers enable a range of new strategies in quantum device research and scaling by increasing the device count while limiting the number of connections between room-temperature control electronics and the cryogenic samples. As an example of this potential we perform a statistical characterization of large arrays of identical quantum dots thus establishing the feasibility of applying cross-bar gating strategies for efficient scaling of future selective area growth quantum circuits. More broadly, the ability to systematically characterise large numbers of devices provides new levels of statistical certainty to materials/device development.

Muscarinic acetylcholine receptors M2 are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Background: Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone. Aim: To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M2) and the G protein-gated inwardly rectifying K+ (GIRK4) channel that mediates the cardiac IK,ACh current. Method: Eighteen horses with a low burden of second-degree AV block (median 8 block per 20 h, IQR: 32 per 20 h) were assigned to the control group, while 17 horses with a high burden of second-degree AV block (median: 408 block per 20 h, IQR: 1,436 per 20 h) were assigned to the AV block group. Radiotelemetry ECG recordings were performed to assess PR interval and incidence of second-degree AV block episodes at baseline and on pharmacological blockade of the autonomic nervous system (ANS). Wenckebach cycle length was measured by intracardiac pacing (n = 16). Furthermore, the expression levels of the M2 receptor and the GIRK4 subunit of the IKACh channel were quantified in biopsies from the right atrium, the AV node and right ventricle using immunohistochemistry and machine learning-based automated segmentation analysis (n = 9 + 9). Results: The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05 s; p < 0.001) and a longer Wenckebach cycle length (mean ± SD, 995 ± 86 ms; p = 0.007) at baseline. After blocking the ANS, all second-degree AV block episodes were abolished, and the difference in PR interval disappered (p = 0.80). The AV block group had significantly higher expression of the M2 receptor (p = 0.02), but not the GIRK4 (p = 0.25) in the AV node compared to the control group. Both M2 and GIRK4 were highly expressed in the AV node and less expressed in the atria and the ventricles. Conclusion: Here, we demonstrate the involvement of the m2R-IK,ACh pathway in underlying second-degree AV block in horses. The high expression level of the M2 receptor may be responsible for the high burden of second-degree AV blocks seen in some horses.

Epitaxially Driven Phase Selectivity of Sn in Hybrid Quantum Nanowires.

Hybrid semiconductor-superconductor nanowires constitute a pervasive platform for studying gate-tunable superconductivity and the emergence of topological behavior. Their low dimensionality and crystal structure flexibility facilitate unique heterostructure growth and efficient material optimization, crucial prerequisites for accurately constructing complex multicomponent quantum materials. Here, we present an extensive study of Sn growth on InSb, InAsSb, and InAs nanowires and demonstrate how the crystal structure of the nanowires drives the formation of either semimetallic α-Sn or superconducting ß-Sn. For InAs nanowires, we observe phase-pure superconducting ß-Sn shells. However, for InSb and InAsSb nanowires, an initial epitaxial α-Sn phase evolves into a polycrystalline shell of coexisting α and ß phases, where the ß/α volume ratio increases with Sn shell thickness. Whether these nanowires exhibit superconductivity or not critically relies on the ß-Sn content. Therefore, this work provides key insights into Sn phases on a variety of semiconductors with consequences for the yield of superconducting hybrids suitable for generating topological systems.

Left atrial functional measurements' utility in predicting long-term risk of atrial fibrillation after isolated CABG.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia following coronary artery bypass grafting (CABG). We hypothesized that measures of left atrial (LA) function would be useful in predicting AF in patients undergoing CABG. METHODS AND RESULTS: In the study, 611 patients were included after CABG. All patients had echocardiograms performed preoperatively and LA functional measurements were assessed. These measurements were LA maximum volume index (LAVmax), LA minimum volume index (LAVmin) and LA emptying fraction (LAEF). The endpoint was AF occurring >14 days after surgery. During the follow-up period of a median of 3.7 years, 52 (9%) developed AF. The mean age was 67 years, 84% were male and the average left ventricle ejection fraction was 50%. Patients who developed AF had a lower CCS class and lower LAEF (40 vs. 45%), otherwise no clinical differences were observed between outcome groups. No functional LA measurements were significant predictors of AF in the whole CABG population. However, in patients with normal-sized LA (n = 532, events: 49), both LAEF and LAVmin were univariable predictors of AF. When the functional measurements were adjusted for the CHADS2 score, both LAVmin (HR = 1.07 [1.01-1.13], p = .014) and LAEF (HR: 1.02 [1.00-1.03], p = .023), remained significant predictors. CONCLUSION: No echocardiographic measurements were significant predictors of AF after CABG. In patients with a normal LA size, LAVmin as well as LAEF were significant predictors of AF.

Long-Term Training Increases Atrial Fibrillation Sustainability in Standardbred Racehorses.

Atrial fibrillation (AF) is more prevalent in athletes, and currently, the mechanisms are not fully understood. Atrial fibrillation inducibility and stability was investigated in trained and untrained Standardbred racehorses. The horses underwent echocardiography for evaluation of atrial size. High-density mapping during AF was performed, and the presence of structural remodeling, as well as the expression of inflammatory and pro-inflammatory markers in the atria, was studied. Atrial fibrillation sustained significantly longer after tachypacing in the trained horses, whereas no difference in AF inducibility was found. The untrained horses displayed a significant difference in the AF complexity when comparing right and left atria, whereas such difference was not observed in the trained animals. No evidence of increased structural remodeling or inflammation could be identified. Left atrial dimensions were not significantly increased. The increased AF sustainability in trained horses was not related to fibrosis or inflammation as seen in other animal exercise models.

Nanopore sequencing reveals methylation changes associated with obesity in circulating cell-free DNA from Göttingen Minipigs.

Profiling of circulating cell-free DNA (cfDNA) by tissue-specific base modifications, such as 5-methylcytosines (5mC), may enable the monitoring of ongoing pathophysiological processes. Nanopore sequencing allows genome-wide 5mC detection in cfDNA without bisulphite conversion. The aims of this study were: i) to find differentially methylated regions (DMRs) of cfDNA associated with obesity in Göttingen minipigs using Nanopore sequencing, ii) to validate a subset of the DMRs using methylation-specific PCR (MSP-PCR), and iii) to compare the cfDNA DMRs with those from whole blood genomic DNA (gDNA). Serum cfDNA and gDNA were obtained from 10 lean and 7 obese Göttingen Minipigs both with experimentally induced myocardial infarction and sequenced using Oxford Nanopore MinION. A total of 1,236 cfDNA DMRs (FDR<0.01) were associated with obesity. In silico analysis showed enrichment of the adipocytokine signalling, glucagon signalling, and cellular glucose homoeostasis pathways. A strong cfDNA DMR was discovered in PPARGC1B, a gene linked to obesity and type 2 diabetes. The DMR was validated using MSP-PCR and correlated significantly with body weight (P < 0.05). No DMRs intersected between cfDNA and gDNA, suggesting that cfDNA originates from body-wide shedding of DNA. In conclusion, nanopore sequencing detected differential methylation in minute quantities (0.1-1 ng/µl) of cfDNA. Future work should focus on translation into human and comparing 5mC from somatic tissues to pinpoint the exact location of pathology.

Oxford nanopore sequencing can reveal changes in methylation patterns associated with obesity in minute quantities of cell-free DNA from serum.Bisulphite conversion and methylation-specific PCR can be used to validate differentially methylated regions in cell-free DNA.A differentially methylated region in an intronic region of the PPARGC1B gene was found associated with obesity.Differentially methylated regions in cell-free DNA could be useful as early risk markers of certain diseases and pathologies.

Enhanced Ca2+-Dependent SK-Channel Gating and Membrane Trafficking in Human Atrial Fibrillation.

BACKGROUND: Small-conductance Ca2+-activated K+ (SK)-channel inhibitors have antiarrhythmic effects in animal models of atrial fibrillation (AF), presenting a potential novel antiarrhythmic option. However, the regulation of SK-channels in human atrial cardiomyocytes and its modification in patients with AF are poorly understood and were the object of this study. METHODS: Apamin-sensitive SK-channel current (ISK) and action potentials were recorded in human right-atrial cardiomyocytes from sinus rhythm control (Ctl) patients or patients with (long-standing persistent) chronic AF (cAF). RESULTS: ISK was significantly higher, and apamin caused larger action potential prolongation in cAF- versus Ctl-cardiomyocytes. Sensitivity analyses in an in silico human atrial cardiomyocyte model identified IK1 and ISK as major regulators of repolarization. Increased ISK in cAF was not associated with increases in mRNA/protein levels of SK-channel subunits in either right- or left-atrial tissue homogenates or right-atrial cardiomyocytes, but the abundance of SK2 at the sarcolemma was larger in cAF versus Ctl in both tissue-slices and cardiomyocytes. Latrunculin-A and primaquine (anterograde and retrograde protein-trafficking inhibitors) eliminated the differences in SK2 membrane levels and ISK between Ctl- and cAF-cardiomyocytes. In addition, the phosphatase-inhibitor okadaic acid reduced ISK amplitude and abolished the difference between Ctl- and cAF-cardiomyocytes, indicating that reduced calmodulin-Thr80 phosphorylation due to increased protein phosphatase-2A levels in the SK-channel complex likely contribute to the greater ISK in cAF-cardiomyocytes. Finally, rapid electrical activation (5 Hz, 10 minutes) of Ctl-cardiomyocytes promoted SK2 membrane-localization, increased ISK and reduced action potential duration, effects greatly attenuated by apamin. Latrunculin-A or primaquine prevented the 5-Hz-induced ISK-upregulation. CONCLUSIONS: ISK is upregulated in patients with cAF due to enhanced channel function, mediated by phosphatase-2A-dependent calmodulin-Thr80 dephosphorylation and tachycardia-dependent enhanced trafficking and targeting of SK-channel subunits to the sarcolemma. The observed AF-associated increases in ISK, which promote reentry-stabilizing action potential duration shortening, suggest an important role for SK-channels in AF auto-promotion and provide a rationale for pursuing the antiarrhythmic effects of SK-channel inhibition in humans.

3D-electroanatomical mapping of the left atrium and catheter-based pulmonary vein isolation in pigs: A practical guide.

Aim: To propose a standardized workflow for 3D-electroanatomical mapping guided pulmonary vein isolation in pigs. Materials and methods: Danish female landrace pigs were anaesthetized. Ultrasound-guided puncture of both femoral veins was performed and arterial access for blood pressure measurement established. Fluoroscopy- and intracardiac ultrasound-guided passage of the patent foramen ovale or transseptal puncture was performed. Then, 3D-electroanatomical mapping of the left atrium was conducted using a high-density mapping catheter. After mapping all pulmonary veins, an irrigated radiofrequency ablation catheter was used to perform ostial ablation to achieve electrical pulmonary vein isolation. Entrance- and exit-block were confirmed and re-assessed after a 20-min waiting period. Lastly, animals were sacrificed to perform left atrial anatomical gross examination. Results: We present data from 11 consecutive pigs undergoing pulmonary vein isolation. Passage of the fossa ovalis or transseptal puncture was uneventful and successful in all animals. Within the inferior pulmonary trunk 2-4 individual veins as well as 1-2 additional left and right pulmonary veins could be cannulated. Electrical isolation by point-by-point ablation of all targeted veins was successful. However, pitfalls including phrenic nerve capture during ablation, ventricular arrhythmias during antral isolation close to the mitral valve annulus and difficulties in accessing right pulmonary veins were encountered. Conclusion: Fluoroscopy- and intracardiac ultrasound-guided transseptal puncture, high-density electroanatomical mapping of all pulmonary veins and complete electrical pulmonary vein isolation can be achieved reproducibly and safely in pigs when using current technologies and a step-by-step approach.

Adiposity-associated atrial fibrillation: molecular determinants, mechanisms, and clinical significance.

Obesity is an important contributing factor to the pathophysiology of atrial fibrillation (AF) and its complications by causing systemic changes, such as altered haemodynamic, increased sympathetic tone, and low-grade chronic inflammatory state. In addition, adipose tissue is a metabolically active organ that comprises various types of fat deposits with discrete composition and localization that show distinct functions. Fatty tissue differentially affects the evolution of AF, with highly secretory active visceral fat surrounding the heart generally having a more potent influence than the rather inert subcutaneous fat. A variety of proinflammatory, profibrotic, and vasoconstrictive mediators are secreted by adipose tissue, particularly originating from cardiac fat, that promote atrial remodelling and increase the susceptibility to AF. In this review, we address the role of obesity-related factors and in particular specific adipose tissue depots in driving AF risk. We discuss the distinct effects of key secreted adipokines from different adipose tissue depots and their participation in cardiac remodelling. The possible mechanistic basis and molecular determinants of adiposity-related AF are discussed, and finally, we highlight important gaps in current knowledge, areas requiring future investigation, and implications for clinical management.

Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events.

BACKGROUND: Obstructive sleep apnea (OSA) creates a complex substrate for atrial fibrillation (AF), which is refractory to many clinically available pharmacological interventions. We investigated atrial antiarrhythmogenic properties and ventricular electrophysiological safety of small-conductance Ca2+ -activated K+ (SK)-channel inhibition in a porcine model for obstructive respiratory events. METHODS: In spontaneously breathing pigs, obstructive respiratory events were simulated by intermittent negative upper airway pressure (INAP) applied via a pressure device connected to the intubation tube. INAP was applied for 75 s, every 10 min, three times before and three times during infusion of the SK-channel inhibitor AP14145. Atrial effective refractory periods (AERP) were acquired before (pre-INAP), during (INAP) and after (post-) INAP. AF-inducibility was determined by a S1S2 atrial pacing protocol. Ventricular arrhythmicity was evaluated by heart rate adjusted QT-interval duration (QT-paced) and electromechanical window (EMW) shortening. RESULTS: During vehicle infusion, INAP transiently shortened AERP (pre-INAP: 135 ± 10 ms vs. post-INAP 101 ± 11 ms; p = .008) and increased AF-inducibility. QT-paced prolonged during INAP (pre-INAP 270 ± 7 ms vs. INAP 275 ± 7 ms; p = .04) and EMW shortened progressively throughout INAP and post-INAP (pre-INAP 80 ± 4 ms; INAP 59 ± 6 ms, post-INAP 46 ± 10 ms). AP14145 prolonged baseline AERP, partially prevented INAP-induced AERP-shortening and reduced AF-susceptibility. AP14145 did not alter QT-paced at baseline (pre-AP14145 270 ± 7 ms vs. AP14145 268 ± 6 ms, p = .83) or QT-paced and EMW-shortening during INAP. CONCLUSION: In a pig model for obstructive respiratory events, the SK-channel-inhibitor AP14145 prevented INAP-associated AERP-shortening and AF-susceptibility without impairing ventricular electrophysiology. Whether SK-channels represent a target for OSA-related AF in humans warrants further study.

Cartilaginous Intrusion of the Atrioventricular Node in a Quarter Horse with a High Burden of Second-Degree AV Block and Collapse: A Case Report.

Second-degree atrioventricular (AV) block is the most common cardiac arrhythmia in horses, affecting 40-90% depending on breed. Usually, the AV blocks occur while the horses are resting and disappear upon exercise and are, therefore, considered to be uneventful for horses. However, if the AV blocks occur frequently, this may result in syncope and collapse. Identifying the cause of second-degree AV block is difficult and often subscribed to high vagal tone. In this report, we present an eight-year-old Quarter horse with a high burden of second-degree AV blocks and multiple collapses. The clinical examination, including neurological examination, blood analysis, 24-h ECG recording and cardiac echocardiography, did not reveal any signs of general or cardiovascular disease besides a high burden of second-degree AV blocks (~300 blocks per hour) and a hyperechoic area in the AV nodal region. An implantable loop recorder (ILR) was inserted to monitor the cardiac rhythm. The ILR detected several consecutive second-degree AV blocks and pauses above 5 s. However, unfortunately, no recordings were available during the collapses. Eventually, the horse was euthanized and the heart inspected. The aortic root was severely cartilaginous and appeared to penetrate the AV node, especially in the His bundle region, possibly explaining the hampered AV conduction. Nevertheless, it is still uncertain if the AV nodal disruption caused the collapses and more knowledge on AV nodal diseases in horses is warranted.

InAs/MoRe Hybrid Semiconductor/Superconductor Nanowire Devices.

Implementing superconductors capable of proximity-inducing a large energy gap in semiconductors in the presence of strong magnetic fields is a major goal toward applications of semiconductor/superconductor hybrid materials in future quantum information technologies. Here, we study the performance of devices consisting of InAs nanowires in electrical contact with molybdenum-rhenium (MoRe) superconducting alloys. The MoRe thin films exhibit transition temperatures of ∼10 K and critical fields exceeding 6 T. Normal/superconductor devices enabled tunnel spectroscopy of the corresponding induced superconductivity, which was maintained up to ∼10 K, and MoRe-based Josephson devices exhibited supercurrents and multiple Andreev reflections. We determine an induced superconducting gap lower than expected from the transition temperature and observe gap softening at finite magnetic field. These may be common features for hybrids based on large-gap, type II superconductors. The results encourage further development of MoRe-based hybrids.

Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue.

The physiological importance of NCX in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is not well characterized but may depend on the relative strength of the current, compared to adult cardiomyocytes, and on the exact spatial arrangement of proteins involved in Ca2+ extrusion. Here, we determined NCX currents and its contribution to action potential and force in hiPSC-CMs cultured in engineered heart tissue (EHT). The results were compared with data from rat and human left ventricular tissue. The NCX currents in hiPSC-CMs were larger than in ventricular cardiomyocytes isolated from human left ventricles (1.3 ± 0.2 pA/pF and 3.2 ± 0.2 pA/pF for human ventricle and EHT, respectively, p < 0.05). SEA0400 (10 µM) markedly shortened the APD90 in EHT (by 26.6 ± 5%, p < 0.05) and, to a lesser extent, in rat ventricular tissue (by 10.7 ± 1.6%, p < 0.05). Shortening in human left ventricular preparations was small and not different from time-matched controls (TMCs; p > 0.05). Force was increased by the NCX block in rat ventricle (by 31 ± 5.4%, p < 0.05) and EHT (by 20.8 ± 3.9%, p < 0.05), but not in human left ventricular preparations. In conclusion, hiPSC-CMs possess NCX currents not smaller than human left ventricular tissue. Robust NCX block-induced APD shortening and inotropy makes EHT an attractive pharmacological model.

Photon-Assisted Tunneling of High-Order Multiple Andreev Reflections in Epitaxial Nanowire Josephson Junctions.

Semiconductor/superconductor hybrids exhibit a range of phenomena that can be exploited for the study of novel physics and the development of new technologies. Understanding the origin of the energy spectrum of such hybrids is therefore a crucial goal. Here, we study Josephson junctions defined by shadow epitaxy on InAsSb/Al nanowires. The devices exhibit gate-tunable supercurrents at low temperatures and multiple Andreev reflections (MARs) at finite voltage bias. Under microwave irradiation, photon-assisted tunneling (PAT) of MARs produces characteristic oscillating sidebands at quantized energies, which depend on MAR order, n, in agreement with a recently suggested modification of the classical Tien-Gordon equation. The scaling of the quantized energy spacings with microwave frequency provides independent confirmation of the effective charge, ne, transferred by the nth-order tunneling process. The measurements suggest PAT as a powerful method for assigning the origin of low-energy spectral features in hybrid Josephson devices.

Stacking and Twisting of Freestanding Complex Oxide Thin Films.

The integration of dissimilar materials in heterostructures has long been a cornerstone of modern materials science-seminal examples are 2D materials and van der Waals heterostructures. Recently, new methods have been developed that enable the realization of ultrathin freestanding oxide films approaching the 2D limit. Oxides offer new degrees of freedom, due to the strong electronic interactions, especially the 3d orbital electrons, which give rise to rich exotic phases. Inspired by this progress, a new platform for assembling freestanding oxide thin films with different materials and orientations into artificial stacks with heterointerfaces is developed. It is shown that the oxide stacks can be tailored by controlling the stacking sequences, as well as the twist angle between the constituent layers with atomically sharp interfaces, leading to distinct moiré patterns in the transmission electron microscopy images of the full stacks. Stacking and twisting is recognized as a key degree of structural freedom in 2D materials but, until now, has never been realized for oxide materials. This approach opens unexplored avenues for fabricating artificial 3D oxide stacking heterostructures with freestanding membranes across a broad range of complex oxide crystal structures with functionalities not available in conventional 2D materials.

A Two-Dimensional Superconducting Electron Gas in Freestanding LaAlO3/SrTiO3 Micromembranes.

Freestanding oxide membranes constitute an intriguing material platform for new functionalities and allow integration of oxide electronics with technologically important platforms such as silicon. Sambri et al. recently reported a method to fabricate freestanding LaAlO3/SrTiO3 (LAO/STO) membranes by spalling of strained heterostructures. Here, we first develop a scheme for the high-yield fabrication of membrane devices on silicon. Second, we show that the membranes exhibit metallic conductivity and a superconducting phase below ∼200 mK. Using anisotropic magnetotransport we extract the superconducting phase coherence length ξ ≈ 36-80 nm and establish an upper bound on the thickness of the superconducting electron gas d ≈ 17-33 nm, thus confirming its two-dimensional character. Finally, we show that the critical current can be modulated using a silicon-based backgate. The ability to form superconducting nanostructures of LAO/STO membranes, with electronic properties similar to those of the bulk counterpart, opens opportunities for integrating oxide nanoelectronics with silicon-based architectures.

MR-proANP measured at admission is associated with incident atrial fibrillation in STEMI patients.

Atrial fibrillation (AF) is common following ST-segment elevation myocardial infarction (STEMI). Increased blood levels of mid regional pro atrial natriuretic peptide (MR-proANP) have been associated with a greater risk of incident AF. However, knowledge of the value of MR-proANP in predicting incident AF after STEMI is sparse. To assess whether MR-proANP measured at admission is associated with development of incident AF in patients with STEMI. 673 STEMI patients with no history of AF treated with primary percutaneous coronary intervention (pPCI) were prospectively enrolled from September 2006 to December 2008. Blood samples were drawn before the procedure. MR-proANP was measured by an automated processing assay. End point was incident AF. Median follow-up time was 5.5 years (interquartile-range 4.7-6.0), during which 63 patients developed AF. In a multivariable Cox regression model adjusted for relevant clinical and biochemical variables, MR-proANP was significantly associated with the development of AF (HR 1.18 per 100 pmol, 95% CI 1.11-1.28, p < 0.001). In a subgroup of patients who underwent echocardiography (N = 360), MR-proANP remained significantly associated with the development of AF (HR 1.39 per 100 pmol, 95% CI 1.13-1.71, p = 0.002) after adjusting for clinical and biochemical variables and left ventricular ejection fraction. When stratifying patients according to tertiles of MR-proANP, patients in the upper tertile displayed an 11 times greater risk of developing AF during follow-up as compared to patients in the lower tertile (HR 11.1, 95% CI 4.4-28.2, p < 0.001). Plasma MR-proANP measured at admission is an independent predictor of incident AF after STEMI.