All-Microwave Leakage Reduction Units for Quantum Error Correction with Superconducting Transmon Qubits.

Minimizing leakage from computational states is a challenge when using many-level systems like superconducting quantum circuits as qubits. We realize and extend the quantum-hardware-efficient, all-microwave leakage reduction unit (LRU) for transmons in a circuit QED architecture proposed by Battistel et al. This LRU effectively reduces leakage in the second- and third-excited transmon states with up to 99% efficacy in 220 ns, with minimum impact on the qubit subspace.

Autonomic regulation therapy in chronic heart failure with preserved/mildly reduced ejection fraction: ANTHEM-HFpEF study results.

Background: Autonomic regulation therapy (ART) utilizing cervical vagus nerve stimulation (VNS) appeared to be safe and to improve autonomic tone, symptoms, and cardiac mechanical function in patients with symptomatic heart failure and reduced ejection fraction in the ANTHEM-HF Study. The ANTHEM-HFpEF Study is the first investigation to evaluate the safety and feasibility of ART in patients with symptomatic heart failure and preserved or mildly reduced ejection fraction (HFpEF, HFmrEF).

Methods: This open-label interventional study enrolled 52 patients with HFpEF or HFmrEF, NYHA Class II-III, and LVEF ≥40%, who received stable guideline-directed medical therapy.

Advances in Our Clinical Understanding of Autonomic Regulation Therapy Using Vagal Nerve Stimulation in Patients Living With Heart Failure.

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to the natural operating frequency of the vagus nerve. Among prior studies, the ANTHEM-HF Pilot Study has provided the clearest evidence of autonomic engagement with VNS that was delivered using a stimulation frequency that was within the operating range of the vagus nerve.

Persistent Autonomic Engagement and Cardiac Control After Four or More Years of Autonomic Regulation Therapy Using Vagus Nerve Stimulation.

Introduction: Although heart failure (HF) outcomes have improved dramatically with the use of guideline directed medical therapy and implantable devices, the overall prognosis of patients with HF and reduced ejection fraction (HFrEF) remains poor. Autonomic Regulation Therapy (ART) using chronic vagus nerve stimulation (VNS) has been evaluated in the ANTHEM-HF study, using changes in heart rate (HR) dynamics as a biomarker of autonomic nervous system engagement and cardiac control to guide VNS titration. ART was associated with sustained improvement in cardiac function and HF symptoms in patients with HFrEF and persistent HF symptoms despite guideline-directed medical therapy (GDMT).

Therapeutic responsiveness to vagus nerve stimulation in patients receiving beta-blockade for heart failure with reduced ejection fraction.

Background: The effect of beta-blockade (BB) on response to vagus nerve stimulation (VNS) has not been reported in patients with heart failure and reduced ejection fraction (HFrEF). In the ANTHEM-HF Study, 60 patients received chronic cervical VNS. Background pharmacological therapy remained unchanged during the study, and VNS intensity was stable once up-titrated.

Implantable vagus nerve stimulation system performance is not affected by internal or external defibrillation shocks.

Purpose: Autonomic regulation therapy (ART) for heart failure (HF) is delivered using vagus nerve stimulation (VNS), and has been associated with improvement in cardiac function and HF symptoms. VNS is delivered using an implantable pulse generator (IPG) and a lead placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on VNS system performance.

High-Fidelity Controlled-Z Gate with Maximal Intermediate Leakage Operating at the Speed Limit in a Superconducting Quantum Processor.

Simple tuneup of fast two-qubit gates is essential for the scaling of quantum processors. We introduce the sudden variant (SNZ) of the net zero scheme realizing controlled-Z (CZ) gates by flux control of transmon frequency. SNZ CZ gates realized in a multitransmon processor operate at the speed limit of transverse coupling between computational and noncomputational states by maximizing intermediate leakage.

Effect of defibrillation on the performance of an implantable vagus nerve stimulation system.

Background: Vagus Nerve Stimulation (VNS) delivers Autonomic Regulation Therapy (ART) for heart failure (HF), and has been associated with improvement in cardiac function and heart failure symptoms. VNS is delivered using an implantable pulse generator (IPG) and lead with electrodes placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on the VNS system.

Vagus Nerve Stimulation Provides Multiyear Improvements in Autonomic Function and Cardiac Electrical Stability in the ANTHEM-HF Study.

Background: Patients with heart failure with reduced left ventricular ejection fraction (LVEF) (HFrEF) experience long-term deterioration of autonomic function and cardiac electrical stability linked to increased mortality risk. The Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure (ANTHEM-HF) trial reported improved heart rate variability (HRV) and heart rate turbulence (HRT) and reduced T-wave alternans (TWA) after 12 months of vagus nerve stimulation (VNS). We investigated whether the benefits of chronic VNS persist in the long term.

Long-term Follow-Up of Patients with Heart Failure and Reduced Ejection Fraction Receiving Autonomic Regulation Therapy in the ANTHEM-HF Pilot Study.

Background: The ANTHEM-HF pilot study was an open-label study that evaluated the safety and feasibility of autonomic regulation therapy (ART) utilizing cervical vagus nerve stimulation (VNS) for patients with chronic HF with reduced EF (HFrEF). Patients in NYHA class II-III with EF ≤40% (n = 60) received ART for 6 months post-titration. ART was associated with sustained improvement in left ventricular (LV) function and HF symptoms at 6 and 12 months.

Baseline NT-proBNP and responsiveness to autonomic regulation therapy in patients with heart failure and reduced ejection fraction.

Background: Recent heart failure studies have associated lower baseline natriuretic peptide levels with improved morbidity/mortality outcomes during pharmaceutical treatment, and better clinical outcomes during neuromodulation (NM) with carotid nerve plexus stimulation for HFrEF when NT-proBNP < 1600 pg/ml. Whether baseline NT-proBNP is associated with HFrEF responsiveness to NM using vagus nerve stimulation (VNS) has not been examined. Hence, we evaluated the interaction of baseline NT-proBNP with changes in symptoms and function that occurred during chronic VNS in the ANTHEM-HF study.

Protecting quantum entanglement from leakage and qubit errors via repetitive parity measurements.

Protecting quantum information from errors is essential for large-scale quantum computation. Quantum error correction (QEC) encodes information in entangled states of many qubits and performs parity measurements to identify errors without destroying the encoded information. However, traditional QEC cannot handle leakage from the qubit computational space.

Enhanced ER-associated degradation of HMG CoA reductase causes embryonic lethality associated with deficiency.

UbiA prenyltransferase domain-containing protein-1 (UBIAD1) synthesizes the vitamin K subtype menaquinone-4 (MK-4). Previous studies in cultured cells (Schumacher et al., 2015) revealed that UBIAD1 also inhibits endoplasmic reticulum (ER)-associated degradation (ERAD) of ubiquitinated HMG CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway that produces cholesterol and essential nonsterol isoprenoids.

Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM-HF, INOVATE-HF, and NECTAR-HF.

Aims: Clinical studies of vagal nerve stimulation (VNS) for heart failure with reduced ejection fraction have had mixed results to date. We sought to compare VNS delivery and associated changes in symptoms and function in autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure (ANTHEM-HF), increase of vagal tone in heart failure (INOVATE-HF), and neural cardiac therapy for heart failure (NECTAR-HF) for hypothesis generation.

Methods And Results: Descriptive statistics were used to analyse data from the public domain for differences in proportions using Pearson's chi-square test, differences in mean values using Student's unpaired t-test, and differences in changes of mean values using two-sample t-tests.

Impact of Autonomic Regulation Therapy in Patients with Heart Failure: ANTHEM-HFrEF Pivotal Study Design.

Background: The ANTHEM-HFrEF (Autonomic Regulation Therapy to Enhance Myocardial Function and Reduce Progression of Heart Failure with Reduced Ejection Fraction) pivotal study is an adaptive, open-label, randomized, controlled study evaluating whether autonomic regulation therapy will benefit patients with advanced HFrEF. While early-phase studies have supported potential use of vagus nerve stimulation to deliver autonomic regulation therapy for HFrEF, results of larger clinical trials have been inconsistent. The ANTHEM-HFrEF study uses a novel design, with adaptive sample size selection, evaluating effects on morbidity and mortality as well as symptoms and function.

Fast, High-Fidelity Conditional-Phase Gate Exploiting Leakage Interference in Weakly Anharmonic Superconducting Qubits.

Conditional-phase (cz) gates in transmons can be realized by flux pulsing computational states towards resonance with noncomputational ones. We present a 40 ns cz gate based on a bipolar flux pulse suppressing leakage (0.1%) by interference and approaching the speed limit set by exchange coupling.

Background pharmacological therapy in the ANTHEM-HF: comparison to contemporary trials of novel heart failure therapies.

Aims: Clinical trials of new heart failure (HF) therapies administer guideline-directed medical therapy (GDMT) as background pharmacologic treatment (BPT). In the ANTHEM-HF Pilot Study, addition of autonomic regulation therapy to GDMT significantly improved left ventricular function, New York Heart Association (NYHA) class, 6 min walk distance, and quality of life in patients with HF with reduced ejection fraction (HFrEF). A post hoc analysis was performed to compare BPT in ANTHEM-HF with two other trials of novel HF therapies: the PARADIGM-HF study of sacubitril-valsartan and the SHIFT study of ivadrabine.

Evolution of Nanowire Transmon Qubits and Their Coherence in a Magnetic Field.

We present an experimental study of flux- and gate-tunable nanowire transmons with state-of-the-art relaxation time allowing quantitative extraction of flux and charge noise coupling to the Josephson energy. We evidence coherence sweet spots for charge, tuned by voltage on a proximal side gate, where first order sensitivity to switching two-level systems and background 1/f noise is minimized. Next, we investigate the evolution of a nanowire transmon in a parallel magnetic field up to 70 mT, the upper bound set by the closing of the induced gap.

Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM-HFpEF study.

Background: Approximately half of the patients presenting with new-onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid-range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta-blockers and angiotensin-converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy.

Experimentally simulating the dynamics of quantum light and matter at deep-strong coupling.

The quantum Rabi model describing the fundamental interaction between light and matter is a cornerstone of quantum physics. It predicts exotic phenomena like quantum phase transitions and ground-state entanglement in ultrastrong and deep-strong coupling regimes, where coupling strengths are comparable to or larger than subsystem energies. Demonstrating dynamics remains an outstanding challenge, the few experiments reaching these regimes being limited to spectroscopy.

The stability of the transcriptome during the estrous cycle in four regions of the mouse brain.

We analyzed the transcriptome of the C57BL/6J mouse hypothalamus, hippocampus, neocortex, and cerebellum to determine estrous cycle-specific changes in these four brain regions. We found almost 16,000 genes are present in one or more of the brain areas but only 210 genes, ∼1.3%, are significantly changed as a result of the estrous cycle.

The Dilemma of Breast Cancer Treatment and Existing Collagen Vascular Disease: A Case of Scleroderma and Review of the Literature.

Collagen vascular diseases present a treatment dilemma for patients with breast cancer. Due to the potential for severe, acute, and late complications of radiation therapy, a history of collagen vascular disease (CVD) is a relative contraindication to breast-conserving treatment. We present a case of early stage breast cancer in a patient with severe scleroderma treated with breast-conserving surgery without radiation and a brief review of the published literature regarding the therapeutic approach to the patient with CVD and breast cancer.

Safety, pharmacokinetics, and pharmacodynamics of PD 0348292, an oral, direct factor Xa inhibitor, after single and multiple dosings in healthy subjects.

Objective: The objective of this study was to evaluate PD 0348292 safety, pharmacokinetics, and pharmacodynamics in healthy subjects.

Methods: Three phase 1 studies were conducted. Studies 1001 and 1021 were single ascending-dose studies in healthy subjects randomized to oral PD 0348292 (2.

Medication adherence and activity patterns underlying uncontrolled hypertension: Assessment and recommendations by practicing pharmacists using digital health care.

Objectives: This report summarizes the first use of a digital health feedback system (DHFS) by practicing pharmacists to establish evidence-based blood pressure (BP) management recommendations.

Setting: Fifteen commercial pharmacies and 39 patients in the Isle of Wight participated.

Practice Description: The pharmacists were experienced in providing New Medicine Services to patients in their communities.