A single dose of AC102 restores hearing in a guinea pig model of noise-induced hearing loss to almost prenoise levels.

Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically. Here, we demonstrate that a single interventive application of a small pyridoindole molecule (AC102) into the middle ear restored auditory function almost to prenoise levels in a guinea pig model of NIHL. AC102 prevented noise-triggered loss of OHCs and reduced IHC synaptopathy suggesting a role of AC102 in reconnecting auditory neurons to their sensory target cells. Notably, AC102 exerted its therapeutic properties over a wide frequency range. Such strong improvements in hearing have not previously been demonstrated for other therapeutic agents. In vitro experiments of a neuronal damage model revealed that AC102 protected cells from apoptosis and promoted neurite growth. These effects may be explained by increased production of adenosine triphosphate, indicating improved mitochondrial function, and reduced levels of reactive-oxygen species which prevents the apoptotic processes responsible for OHC death. This action profile of AC102 might be causal for the observed hearing recovery in in vivo models.

Strong transient magnetic fields induced by THz-driven plasmons in graphene disks.

Strong circularly polarized excitation opens up the possibility to generate and control effective magnetic fields in solid state systems, e.g., via the optical inverse Faraday effect or the phonon inverse Faraday effect. While these effects rely on material properties that can be tailored only to a limited degree, plasmonic resonances can be fully controlled by choosing proper dimensions and carrier concentrations. Plasmon resonances provide new degrees of freedom that can be used to tune or enhance the light-induced magnetic field in engineered metamaterials. Here we employ graphene disks to demonstrate light-induced transient magnetic fields from a plasmonic circular current with extremely high efficiency. The effective magnetic field at the plasmon resonance frequency of the graphene disks (3.5 THz) is evidenced by a strong ( ~ 1°) ultrafast Faraday rotation ( ~ 20 ps). In accordance with reference measurements and simulations, we estimated the strength of the induced magnetic field to be on the order of 0.7 T under a moderate pump fluence of about 440 nJ cm-2.

Ultrafast hot-carrier cooling in quasi freestanding bilayer graphene with hydrogen intercalated atoms.

Femtosecond-THz optical pump probe spectroscopy is employed to investigate the cooling dynamics of hot carriers in quasi-free standing bilayer epitaxial graphene with hydrogen interacalation. We observe longer decay time constants, in the range of 2.6 to 6.4 ps, compared to previous studies on monolayer graphene, which increase nonlinearly with excitation intensity. The increased relaxation times are due to the decoupling of the graphene layer from the SiC substrate after hydrogen intercalation which increases the distance between graphene and substrate. Furthermore, our measurements show that the supercollision mechanism is not related to the cooling process of the hot carriers, which is ultimately achieved by electron optical phonon scattering.

Nail Sarcoidosis.

This case report describes significant longitudinal ridging and nail plate crumbling on several of a patient's fingernails.

Modifications of Epitaxial Graphene on SiC for the Electrochemical Detection and Identification of Heavy Metal Salts in Seawater.

The electrochemical detection of heavy metal ions is reported using an inexpensive portable in-house built potentiostat and epitaxial graphene. Monolayer, hydrogen-intercalated quasi-freestanding bilayer, and multilayer epitaxial graphene were each tested as working electrodes before and after modification with an oxygen plasma etch to introduce oxygen chemical groups to the surface. The graphene samples were characterized using X-ray photoelectron spectroscopy, atomic force microscopy, Raman spectroscopy, and van der Pauw Hall measurements. Dose-response curves in seawater were evaluated with added trace levels of four heavy metal salts (CdCl2, CuSO4, HgCl2, and PbCl2), along with detection algorithms based on machine learning and library development for each form of graphene and its oxygen plasma modification. Oxygen plasma-modified, hydrogen-intercalated quasi-freestanding bilayer epitaxial graphene was found to perform best for correctly identifying heavy metals in seawater.

Phonon assisted electron emission from quasi-freestanding bilayer epitaxial graphene microstructures.

Electron emission from quasi-freestanding bilayer epitaxial graphene (QFEG) on a silicon carbide substrate is reported, demonstrating emission currents as high as 8.5µA, at ∼200 °C, under 0.3 Torr vacuum. Given the significantly low turn-on temperature of these QFEG devices, ∼150°C, the electron emission is explained by phonon-assisted electron emission, where the acoustic and optical phonons of QFEG causes carrier acceleration and emission. Devices of differing dimensions and shapes are fabricated via a simple and scalable fabrication procedure and tested. Variations in device morphology increase the density of dangling bonds, which can act as electron emission sites. Devices exhibit emission enhancement at increased temperatures, attributed to greater phonon densities. Devices exhibit emission under various test conditions, and a superior design and operating methodology are identified.

Electrical and Low Frequency Noise Characterization of Graphene Chemical Sensor Devices Having Different Geometries.

Chemiresistive graphene sensors are promising for chemical sensing applications due to their simple device structure, high sensitivity, potential for miniaturization, low-cost, and fast response. In this work, we investigate the effect of (1) ZnO nanoparticle functionalization and (2) engineered defects onto graphene sensing channel on device resistance and low frequency electrical noise. The engineered defects of interest include 2D patterns of squares, stars, and circles and 1D patterns of slots parallel and transverse to the applied electric potential. The goal of this work is to determine which devices are best suited for chemical sensing applications. We find that, relative to pristine graphene devices, nanoparticle functionalization leads to reduced contact resistance but increased sheet resistance. In addition, functionalization lowers 1/f current noise on all but the uniform mesa device and the two devices with graphene strips parallel to carrier transport. The strongest correlations between noise and engineering defects, where normalized noise amplitude as a function of frequency f is described by a model of AN/fγ, are that γ increases with graphene area and contact area but decreases with device total perimeter, including internal features. We did not find evidence of a correlation between the scalar amplitude, AN, and the device channel geometries. In general, for a given device area, the least noise was observed on the least-etched device. These results will lead to an understanding of what features are needed to obtain the optimal device resistance and how to reduce the 1/f noise which will lead to improved sensor performance.

Pericyte heterogeneity identified by 3D ultrastructural analysis of the microvessel wall.

Confident identification of pericytes (PCs) remains an obstacle in the field, as a single molecular marker for these unique perivascular cells remains elusive. Adding to this challenge is the recent appreciation that PC populations may be heterogeneous, displaying a range of morphologies within capillary networks. We found additional support on the ultrastructural level for the classification of these PC subtypes-"thin-strand" (TSP), mesh (MP), and ensheathing (EP)-based on distinct morphological characteristics. Interestingly, we also found several examples of another cell type, likely a vascular smooth muscle cell, in a medial layer between endothelial cells (ECs) and pericytes (PCs) harboring characteristics of the ensheathing type. A conserved feature across the different PC subtypes was the presence of extracellular matrix (ECM) surrounding the vascular unit and distributed in between neighboring cells. The thickness of this vascular basement membrane was remarkably consistent depending on its location, but never strayed beyond a range of 150-300 nm unless thinned to facilitate closer proximity of neighboring cells (suggesting direct contact). The density of PC-EC contact points ("peg-and-socket" structures) was another distinguishing feature across the different PC subtypes, as were the apparent contact locations between vascular cells and brain parenchymal cells. In addition to this thinning, the extracellular matrix (ECM) surrounding EPs displayed another unique configuration in the form of extensions that emitted out radially into the surrounding parenchyma. Knowledge of the origin and function of these structures is still emerging, but their appearance suggests the potential for being mechanical elements and/or perhaps signaling nodes via embedded molecular cues. Overall, this unique ultrastructural perspective provides new insights into PC heterogeneity and the presence of medial cells within the microvessel wall, the consideration of extracellular matrix (ECM) coverage as another PC identification criteria, and unique extracellular matrix (ECM) configurations (i.e., radial extensions) that may reveal additional aspects of PC heterogeneity.

Real-time ultra-sensitive detection of SARS-CoV-2 by quasi-freestanding epitaxial graphene-based biosensor.

We report the rapid detection of SARS-CoV-2 in infected patients (mid-turbinate swabs and exhaled breath aerosol samples) in concentrations as low as 60 copies/mL of the virus in seconds by electrical transduction of the SARS-CoV-2 S1 spike protein antigen via SARS-CoV-2 S1 spike protein antibodies immobilized on bilayer quasi-freestanding epitaxial graphene without gate or signal amplification. The sensor demonstrates the spike protein antigen detection in a concentration as low as 1 ag/mL. The heterostructure of the SARS-CoV-2 antibody/graphene-based sensor is developed through a simple and low-cost fabrication technique. Furthermore, sensors integrated into a portable testing unit distinguished B.1.1.7 variant positive samples from infected patients (mid-turbinate swabs and saliva samples, 4000-8000 copies/mL) with a response time of as fast as 0.6 s. The sensor is reusable, allowing for reimmobilization of the crosslinker and antibodies on the biosensor after desorption of biomarkers by NaCl solution or heat treatment above 40 °C.

Food Security and Clinical Outcomes of the 2017 Georgia Fruit and Vegetable Prescription Program.

OBJECTIVE: Evaluate improvements in food security and health outcomes associated with participation in a produce prescription program. DESIGN: Program evaluation with repeated measures over 6 months. SETTING: Six sites across Georgia. PARTICIPANTS: Of the 159 enrolled through primary care sites, 122 participants were considered graduates (attended at least 3 of the 6 monthly visits). The majority of program graduates were Black (78.7%), earned <$25,000 annually (76.6%), and were food insecure (74.2%). INTERVENTION: Six-month program offering group-based nutrition and cooking education along with subsidies for fresh produce worth $1 per family member per day, redeemable weekly. MAIN OUTCOME MEASURES: Food security, blood pressure, body mass index, waist circumference, and glycated hemoglobin. ANALYSIS: Linear mixed models estimating association of change in outcomes with program visits 1-6. Fixed effects included participant sex and age, whereas random effects included random intercepts and slopes for the site of program participation and participants. RESULTS: Participation in a produce prescription program combining subsidies for produce and nutrition education decreased food insecurity (P < 0.001) and diastolic blood pressure significantly (P = 0.019). CONCLUSIONS AND IMPLICATIONS: These findings highlight the promise of this program and similar programs for improving patient food security and health outcomes among the most vulnerable, underserved communities while aiding in setting realistic expectations and suggestions for program implementation.

Atopic dermatitis is associated with hidradenitis suppurativa diagnosis: A single institution retrospective cohort study.

BACKGROUND: Hidradenitis suppurativa (HS) and atopic dermatitis (AD) are both chronic inflammatory skin diseases. An association between these 2 conditions can have important potential implications for elucidating pathogenesis, disease course, and treatment. OBJECTIVE: To investigate the association between AD and HS. METHODS: We performed a retrospective cohort study of patients seen at Duke University Medical Center from 2007 to 2017 who had AD compared with a control group without an AD diagnosis. The association of AD and HS was evaluated using a logistic regression model after adjusting for other confounders including age, sex, and race. RESULTS: Of 28,780 patients with an AD diagnosis, 325 (1.1%) were diagnosed with HS compared with 76 (0.2%) within the 48,383 patients in the non-AD group. An adjusted logistic regression model demonstrated an increased odds ratio of having HS diagnosis in the AD group as compared with the control non-AD group (odds ratio: 5.57, 95% confidence interval: 4.30-7.21, P < .001). LIMITATIONS: This was a retrospective study performed at a single institution with the possibility of surveillance bias being present. CONCLUSIONS: Patients with AD are more likely to be diagnosed with HS than patients without AD. Further research is needed to understand the pathophysiologic mechanism and potential treatment implications.

Graphene Buffer Layer on SiC as a Release Layer for High-Quality Freestanding Semiconductor Membranes.

Free-standing crystalline membranes are highly desirable owing to recent developments in heterogeneous integration of dissimilar materials. Van der Waals (vdW) epitaxy enables the release of crystalline membranes from their substrates. However, suppressed nucleation density due to low surface energy has been a challenge for crystallization; reactive materials synthesis environments can induce detrimental damage to vdW surfaces, often leading to failures in membrane release. This work demonstrates a novel platform based on graphitized SiC for fabricating high-quality free-standing membranes. After mechanically removing epitaxial graphene on a graphitized SiC wafer, the quasi-two-dimensional graphene buffer layer (GBL) surface remains intact for epitaxial growth. The reduced vdW gap between the epilayer and substrate enhances epitaxial interaction, promoting remote epitaxy. Significantly improved nucleation and convergent quality of GaN are achieved on the GBL, resulting in the best quality GaN ever grown on two-dimensional materials. The GBL surface exhibits excellent resistance to harsh growth environments, enabling substrate reuse by repeated growth and exfoliation.

Arrays of Si vacancies in 4H-SiC produced by focused Li ion beam implantation.

Point defects in SiC are an attractive platform for quantum information and sensing applications because they provide relatively long spin coherence times, optical spin initialization, and spin-dependent fluorescence readout in a fabrication-friendly semiconductor. The ability to precisely place these defects at the optimal location in a host material with nano-scale accuracy is desirable for integration of these quantum systems with traditional electronic and photonic structures. Here, we demonstrate the precise spatial patterning of arrays of silicon vacancy ([Formula: see text]) emitters in an epitaxial 4H-SiC (0001) layer through mask-less focused ion beam implantation of Li+. We characterize these arrays with high-resolution scanning confocal fluorescence microscopy on the Si-face, observing sharp emission lines primarily coming from the [Formula: see text] zero-phonon line (ZPL). The implantation dose is varied over 3 orders of magnitude, leading to [Formula: see text] densities from a few per implantation spot to thousands per spot, with a linear dependence between ZPL emission and implantation dose. Optically-detected magnetic resonance (ODMR) is also performed, confirming the presence of V2 [Formula: see text]. Our investigation reveals scalable and reproducible defect generation.

Vulvar and perineal verrucous changes complicating hidradenitis suppurativa after wide excision: a case and literature review.

Poorly controlled and long-standing hidradenitis suppurativa (HS) increases the risk of squamous cell carcinoma (SCC). We report a 54-year-old woman with an over 20-year history of HS, who had previously undergone wide perineal excision with secondary intention healing and presented with a painful verrucous vulvar plaque and proximal non-healing perineal wound. The patient had four perineal scouting biopsies performed and excisional biopsy with no evidence of high-grade dysplasia or carcinoma on histology. Chromogenic in situ hybridization was negative for HPV 16 and 18 mRNA; the patient's HIV and HSV PCR were also negative. Our patient was treated with interferon alfa-2b with notable clinical improvement. There is currently no standardized stepwise approach to monitoring verrucous lesions in HS patients with significant risk factors for SCC. Our report highlights a vigilant approach to monitoring. If scouting biopsies are negative, complete testing for high risk HPV strains (HPV 16 and 18) is warranted. If negative, we recommend follow up every 6 months with no further biopsies except if overt clinical changes are observed. We also recommend treatment of verrucous changes to decrease risk of possible malignant conversion. Interferon alfa-2b was effective in decreasing the verrucous lesion burden in our patient and may be considered.

Multilayer Epitaxial Graphene on Silicon Carbide: A Stable Working Electrode for Seawater Samples Spiked with Environmental Contaminants.

The electrochemical response of multilayer epitaxial graphene electrodes on silicon carbide substrates was studied for use as an electrochemical sensor for seawater samples spiked with environmental contaminants using cyclic square wave voltammetry. Results indicate that these graphene working electrodes are more robust and have lower background current than either screen-printed carbon or edge-plane graphite in seawater. Identification algorithms developed using machine learning techniques are described for several heavy metals, herbicides, pesticides, and industrial compounds. Dose-response curves provide a basis for quantitative analysis.

Model-Based Algorithms for Detecting Peripheral Artery Disease Using Administrative Data From an Electronic Health Record Data System: Algorithm Development Study.

BACKGROUND: Peripheral artery disease (PAD) affects 8 to 10 million Americans, who face significantly elevated risks of both mortality and major limb events such as amputation. Unfortunately, PAD is relatively underdiagnosed, undertreated, and underresearched, leading to wide variations in treatment patterns and outcomes. Efforts to improve PAD care and outcomes have been hampered by persistent difficulties identifying patients with PAD for clinical and investigatory purposes. OBJECTIVE: The aim of this study is to develop and validate a model-based algorithm to detect patients with peripheral artery disease (PAD) using data from an electronic health record (EHR) system. METHODS: An initial query of the EHR in a large health system identified all patients with PAD-related diagnosis codes for any encounter during the study period. Clinical adjudication of PAD diagnosis was performed by chart review on a random subgroup. A binary logistic regression to predict PAD was built and validated using a least absolute shrinkage and selection operator (LASSO) approach in the adjudicated patients. The algorithm was then applied to the nonsampled records to further evaluate its performance. RESULTS: The initial EHR data query using 406 diagnostic codes yielded 15,406 patients. Overall, 2500 patients were randomly selected for ground truth PAD status adjudication. In the end, 108 code flags remained after removing rarely- and never-used codes. We entered these code flags plus administrative encounter, imaging, procedure, and specialist flags into a LASSO model. The area under the curve for this model was 0.862. CONCLUSIONS: The algorithm we constructed has two main advantages over other approaches to the identification of patients with PAD. First, it was derived from a broad population of patients with many different PAD manifestations and treatment pathways across a large health system. Second, our model does not rely on clinical notes and can be applied in situations in which only administrative billing data (eg, large administrative data sets) are available. A combination of diagnosis codes and administrative flags can accurately identify patients with PAD in large cohorts.

Major bleeding in patients with peripheral artery disease: Insights from the EUCLID trial.

BACKGROUND: Rates and predictors of major bleeding in patients with peripheral artery disease (PAD) treated with antiplatelets have not been well studied. This post hoc analysis of EUCLID aimed to determine the incidence of major/minor bleeding, predictors of major bleeding, and risk of major adverse cardiovascular events (MACE) following major bleeding events. METHODS: EUCLID, a multicenter randomized controlled trial of 13,885 patients with symptomatic PAD, compared ticagrelor with clopidogrel for the prevention of MACE. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Baseline characteristics were used to develop a multivariable model to determine factors associated with TIMI major bleeding. The occurrence and timing of MACE relative to a first major bleeding event were determined. RESULTS: TIMI major bleeding occurred in 2.3% of participants overall (0.94 event/100 patient-years). There was no significant difference in major bleeding rates by treatment assignment. Factors associated with TIMI major bleeding included older age, geographic region, Rutherford class, and ß-blocker use. Patients with TIMI major bleeding postrandomization had an increased risk of MACE (hazard ratio [HR] 4.46; 95% CI 3.40-5.84; P < .0001) compared with those without major bleeding; the association was strongest within 30 days after a bleeding event. CONCLUSIONS: In patients with symptomatic PAD, 0.94 major bleeding event/100 patient-years was observed and associated with older age, residing in North America, disease severity, and ß-blocker use. Patients who had a major bleeding event were significantly more likely to experience MACE, especially within the first 30 days, when compared with patients who did not have major bleeding.