Superconducting resonators with voltage-controlled frequency and nonlinearity

Voltage-tunable superconductor-semiconductor devices offer a unique platform to realize dynamic tunability in superconducting quantum circuits. By galvanically connecting a gated InAs-Al Josephson junction to a coplanar waveguide resonator, we demonstrate the use of a wide-range gate-tunable superconducting element. We show that the resonant frequency is controlled via a gate-tunable Josephson inductance and that the non-linearity of the voltage-controlled InAs-Al junction is non-dissipative as is the case with conventional Al-AlO$_{x}$ junctions. As the gate voltage is decreased, the inductive participation of the junction increases up to $44\%$, resulting in the resonant frequency being tuned by over 2 GHz. Utilizing the wide tunability of the device, we demonstrate that two resonant modes can be adjusted such that they strongly hybridize, exhibiting an avoided level crossing with a coupling strength of 51 MHz. Implementing such voltage-tunable resonators is the first step toward realizing wafer-scale continuous voltage control in superconducting circuits for qubit-qubit coupling, quantum-limited amplifiers, and quantum memory platforms

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fourteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant R01 DC00126National Institutes of Health Grant R01 DC00270National Institutes of Health Contract N01 DC52107U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-95-1-0176U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0002National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-92-J-184

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Development, validation, and translation of a respiratory motion model-based 4DCT technique for use as a clinical protocol for radiation therapy treatment planning

Breathing motion in radiotherapy is commonly managed with four-dimensional computed tomography (4DCT). 4DCT datasets consist of multiple breathing-gated images that display motion of the subject’s anatomy over a breathing period. Commercial 4DCT protocols aresusceptible to image artifacts when the subject breathes irregularly. Unlike commercial protocols, model-based 4DCT techniques describe a correspondence between tissue motion and an external signal used as a surrogate for respiratory phase. One such technique, termed ’5DCT,’ uses free-breathing fast helical acquisition and characterizes lung tissue motion as function of five degrees of freedom: x,y, and z position in a reference geometry, breathing amplitude, and breathing rate. The overarching goal of this dissertation is to develop the 5DCT technique for clinical use.A validation study was conducted involving comparing 5DCT images to commercial 4DCT using an animal model. Reproducible and periodic breathing patterns were achieved through mechanical ventilation and image similarity was quantified using landmark displacement. Differences in measured tumor motion between 5DCT and commercial 4DCT were examined in a cohort of 20 lung cancer patients. Solutions for the unique challenges of using model model-based techniques clinically, such as appropriate amplitude interval selection and presentation of a quantitative error map, were developed.A quality management program was developed to ensure the safety of the protocol using risk analysis methods such as process mapping and failure modes and effects analysis. In addition, safety of the in-house software required to implement the technique was managed through use cases and quantitative, testable safety requirements. The physiological significance of the 5D model parameters was investigated, particularly their dependence on breathing rate during acquisition. It was shown that the model parameter relating tissue motion to breathing amplitude was largely invariant with breathing rate during acquisition.A prospective scanning method was developed to reduce the number of fast helical scans, and associated imaging dose, necessary to perform 5DCT while maintaining motion modeling accuracy. A simulation study was conducted using patient breathing traces, and the results demonstrated that adequate sampling of the respiratory cycle could be achieved using six scans, compared to the previously published protocol that employs twenty-five

Hodgkin-Huxley Type Modeling

A Hodgkin-Huxley style system of ODEs was developed to model the ion channel activity of A. punctulata sperm flagellum during exposure to resact during chemotaxis. Empirical data was used in conjunction with parameter estimation methods in an attempt for the model to reproduce realistic Voltage potentials and ion concentrations. The change in calcium concentration is of particular interest, as it is essential in the waveform of the flagellum during chemotaxis

Model-Interpolated Gating for Magnetic Resonance Image–Guided Radiation Therapy

PurposeTo develop and validate a technique for radiation therapy gating using slow (≤1 frame per second) magnetic resonance imaging (MRI) and a motion model. Proposed uses of the technique include radiation therapy gating using T2-weighted images and conducting additional imaging studies during gated treatments.Methods and materialsThe technique uses a physiologically guided breathing motion model to interpolate deformed target position between 2-dimensional (2D) MRI images acquired every 1 to 3 seconds. The model is parameterized by a 1-dimensional respiratory bellows surrogate and is continuously updated with the most recently acquired 2D images. A phantom and 8 volunteers were imaged with a 0.35T MRI-guided radiation therapy system. A balanced steady-state free precession sequence with a 2D frame rate of 3 frames per second was used to evaluate the technique. The accuracy and beam-on positive predictive value (PPV) of the model-based gating decisions were evaluated using the gating decisions derived from imaging as a ground truth. A T2-weighted gating offline proof-of-concept study using a half-Fourier, single-shot, turbo-spin echo sequence is reported.ResultsModel-interpolated gating accuracy, beam-on PPV, and median absolute distances between model and image-tracked target centroids were, on average, 98.3%, 98.4%, and 0.33 mm, respectively, in the balanced steady-state free precession phantom studies and 93.7%, 92.1%, and 0.86 mm, respectively, in the volunteer studies. T2 model-interpolated gating in 6 volunteers yielded an average accuracy and PPV of 94.3% and 92.5%, respectively, and the mean absolute median distance between modeled and imaged target centroids was 0.86 mm.ConclusionsThis work demonstrates the concept of model-interpolated gating for MRI-guided radiation therapy. The technique was found to be potentially sufficiently accurate for clinical use. Further development is needed to accommodate out-of-plane motion and the use of an internal MR-based respiratory surrogate