Accuracy and feasibility of an android-based digital assessment tool for post stroke visual disorders - The StrokeVision App

Background: Visual impairment affects up to 70% of stroke survivors. We designed an app (StrokeVision) to facilitate screening for common post stroke visual issues (acuity, visual fields and visual inattention). We sought to describe the test-time, feasibility, acceptability and accuracy of our app based digital visual assessments against a) current methods used for bedside screening, and b) gold standard measures. Methods: Patients were prospectively recruited from acute stroke settings. Index tests were app based assessments of fields and inattention performed by a trained researcher. We compared against usual clinical screening practice of visual fields to confrontation including inattention assessment (simultaneous stimuli). We also compared app to gold standard assessments of formal kinetic perimetry (Goldman or Octopus Visual Field Assessment); and pencil and paper based tests of inattention (Albert’s, Star Cancellation, and Line Bisection). Results of inattention and field tests were adjudicated by a specialist Neuro-Ophthalmologist. All assessors were masked to each other’s results. Participants and assessors graded acceptability using a bespoke scale that ranged from 0 (completely unacceptable) to 10 (perfect acceptability). Results: Of 48 stroke survivors recruited, the complete battery of index and reference tests for fields was successfully completed in 45. Similar acceptability scores were observed for app-based (assessor median score 10 [IQR:9-10]; patient 9 [IQR:8-10]) and traditional bedside testing (assessor 10 [IQR:9-10; patient 10 [IQR:9-10]). Median test time was longer for app-based testing (combined time-to-completion of all digital tests 420 seconds [IQR:390-588]) when compared with conventional bedside testing (70 seconds, [IQR:40-70]) but shorter than gold standard testing (1260 seconds, [IQR:1005-1620]). Compared with gold standard assessments, usual screening practice demonstrated 79% sensitivity and 82% specificity for detection of a stroke-related field defect. This compares with 79% sensitivity and 88% specificity for StrokeVision digital assessment. Conclusion: StrokeVision shows promise as a screening tool for visual complications in the acute phase of stroke. The app is at least as good as usual screening and offers other functionality that may make it attractive for use in acute stroke

Progress toward superconductor electronics fabrication process with planarized NbN and NbN/Nb layers

To increase density of superconductor digital and neuromorphic circuits by 10x and reach integration scale of $10^8$ Josephson junctions (JJs) per chip, we developed a new fabrication process on 200-mm wafers, using self-shunted Nb/Al-AlOx/Nb JJs and kinetic inductors. The process has a layer of JJs, a layer of resistors, and 10 fully planarized superconducting layers: 8 Nb layers and 2 layers of high kinetic inductance materials, Mo$_2$N and NbN, with sheet inductance of 8 pH/sq and 3 pH/sq, respectively. NbN films were deposited by two methods: with $T_c$=15.5 K by reactive sputtering of a Nb target in Ar+N$_2$ mixture; with $T_c$ in the range from 9 K to 13 K by plasma-enhanced chemical vapor deposition (PECVD) using Tris(diethylamido)(tert-butylimido)niobium(V) metalorganic precursor. PECVD of NbN was investigated to obtain conformal deposition and filling narrow trenches and vias with high depth-to-width ratios, which was not possible to achieve using sputtering and other physical vapor deposition (PVD) methods at temperatures below $200 ^oC$ required to prevent degradation of Nb/Al-AlOx/Nb junctions. Nb layers with 200 nm thickness are used in the process layer stack as ground planes to maintain a high level of interlayer shielding and low intralayer mutual coupling, for passive transmission lines with wave impedances matching impedances of JJs, typically <=50 $\Omega$, and for low-value inductors. NbN and NbN/Nb bilayer are used for cell inductors. Using NbN/Nb bilayers and individual pattering of both layers to form inductors allowed us to minimize parasitic kinetic inductance associated with interlayer vias and connections to JJs as well as to increase critical currents of the vias. Fabrication details and results of electrical characterization of NbN films, wires, and vias, and comparison with Nb properties are given.Comment: 12 pages, 16 figures, 4 tables, 49 references. Submitted to IEEE TAS on Nov. 10, 202

Sub-micrometer epitaxial Josephson junctions for quantum circuits

We present a fabrication scheme and testing results for epitaxial sub-micrometer Josephson junctions. The junctions are made using a high-temperature (1170 K) "via process" yielding junctions as small as 0.8 mu m in diameter by use of optical lithography. Sapphire (Al2O3) tunnel-barriers are grown on an epitaxial Re/Ti multilayer base-electrode. We have fabricated devices with both Re and Al top electrodes. While room-temperature (295 K) resistance versus area data are favorable for both types of top electrodes, the low-temperature (50 mK) data show that junctions with the Al top electrode have a much higher subgap resistance. The microwave loss properties of the junctions have been measured by use of superconducting Josephson junction qubits. The results show that high subgap resistance correlates to improved qubit performance

Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies

Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies

Using a genome-scale, lentivirally delivered shRNA library, we performed massively parallel pooled shRNA screens in 216 cancer cell lines to identify genes that are required for cell proliferation and/or viability. Cell line dependencies on 11,000 genes were interrogated by 5 shRNAs per gene. The proliferation effect of each shRNA in each cell line was assessed by transducing a population of 11M cells with one shRNA-virus per cell and determining the relative enrichment or depletion of each of the 54,000 shRNAs after 16 population doublings using Next Generation Sequencing. All the cell lines were screened using standardized conditions to best assess differential genetic dependencies across cell lines. When combined with genomic characterization of these cell lines, this dataset facilitates the linkage of genetic dependencies with specific cellular contexts (e.g., gene mutations or cell lineage). To enable such comparisons, we developed and provided a bioinformatics tool to identify linear and nonlinear correlations between these features

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation