Systems Inc Research Articles

The Influence of Thermomechanical Conditions on the Hot Ductility of Continuously Cast Microalloyed Steels.

Continuous casting is the most common method for producing steel into semi-finished shapes like billets or slabs. Throughout this process, steel experiences mechanical and thermal stresses, which influence its mechanical properties. During continuous casting, decreased formability in steel components leads to crack formation and failure. One reason for this phenomenon is the appearance of the soft ferrite phase during cooling. However, it is unclear under which conditions this ferrite is detrimental to the formability. In the present research, we investigated what microstructural changes decrease the formability of microalloyed steels during continuous casting. We studied the hot compression behaviour of microalloyed steel over temperatures ranging from 650 °C to 1100 °C and strain rates of 0.1 s-1 to 0.001 s-1 using a Gleeble 3800® (Dynamic Systems Inc, Poestenkill, NY, USA) device. We examined microstructural changes at various deformation conditions using microscopy. Furthermore, we implemented a physically-based model to describe the deformation of austenite and ferrite. The model describes the work hardening and dynamic restoration mechanisms, i.e., discontinuous dynamic recrystallisation in austenite and dynamic recovery in ferrite and austenite. The model considers the stress, strain, and strain rate distribution between phases by describing the dynamic phase transformation during the deformation in iso-work conditions. Increasing the strain rate below the transformation temperature improves hot ductility by reducing dynamic recovery and strain concentration in ferrite. Due to limited grain boundary sliding, the hot ductility improves at lower temperatures (<750 °C). In the single-phase domain, dynamic recrystallisation improves the hot ductility provided that fracture occurs at strains in which dynamic recrystallisation advances. However, at very low strain rates, the ductility decreases due to prolonged time for grain boundary sliding and crack propagation.

Early-stage Development of the CoRISMA Mechanical Circulatory Support (CMCS) System for Heart Failure Therapy.

CoRISMA MCS Systems Inc (Hamden CT) is developing an innovative mechanical circulatory support system (CMCS) as a durable therapeutic option for heart failure (HF) patients. The CMCS system is comprised of an axial flow pump, non-contacting hydrodynamic bearings, and integrated DC motor designed to be fully implantable in a left atrial (LA) to aortic (Ao) configuration; this unloading strategy may be particularly beneficial for HF patients with preserved ejection fraction (HFpEF). The small (5.5 cm3), lightweight (20g), and low power (5-7W) device design should allow for a less invasive off-pump implant. We present early-stage engineering development and testing of the prototype CoRISMA pumps. Computational fluid dynamics (CFD) modeling was performed to evaluate flow and shear in two impeller (3 blades, 0.5mm thickness, 8.9mm diameter, 0.15mm gap, polished titanium) and diffusor (5 blades, polished titanium) candidate designs. Test apparatuses were custom built to expedite development of the impeller/diffuser designs and iteratively refine the CFD models. Two candidate impeller/diffusor designs were fabricated and tested in each of the two test apparatuses (n = 4 impeller/diffuser + test fixture configurations) in static mock flow loops (hydrodynamic H-Q curves, 3.5 cP glycerol solution at 37°C), and in dynamic mock flow loops (hemodynamics, 3.5 cP glycerol solution at 37°C) tuned to HF conditions (mean aortic pressure 50 mmHg, central venous pressure 15 mmHg, aortic flow 3.0L/min, and heart rate 80bpm). CFD predicted flows of 4.56L/min and 4.82L/min at 100 mmHg for impellers/diffusers 1 and 2, respectively. Impeller 2 required less torque to generate a 6% increase in fluidic flow, and the diffuser had a larger area of high pressure, indicative of lower friction, which likely contributed to the increased efficiency. Experimental testing for all four configurations in the static and dynamic mock loops met performance metrics as evidenced by generating 4.0-4.5L/min flow against 70-76 mmHg pressure at 25,000rpm and restoring hemodynamics in the dynamic mock flow loop (MAP = 80 mmHg, CVP = 0 mmHg, total flow = 5.5L/min) from baseline simulated HF test conditions. These results demonstrate proof-of-concept of the early engineering design and performance of the prototype CoRISMA pumps. Engineering specifications, challenges observed, and proposed solutions for the next design iteration were identified for the continued development of an effective, reliable, and safe LA-to-Ao CMCS system for HF patients. Current design plans are underway for incorporating a wireless energy transfer system for communication and power, eliminating the need for and complications associated with an external driveline, to achieve a fully-implantable system.

Pre-Operative Planning of a DCR Surgery Using Virtual Reality

ABSTRACT Purpose To assess a novel Virtual Reality (VR) tool designed to enhance understanding of the nasal anatomy in patients eligible for DCR surgery. Methods Preoperative Computed Tomography (CT) scans of the orbit were obtained and loaded as DICOM (Digital Imaging and Communications in Medicine) files onto the D2P software (3D Systems Inc. Littleton, CO) for tissue segmentation and 3D model preparation. Segmentation was performed on several anatomical structures, including the skull, lacrimal sac, nasal septum, inferior and middle turbinate. The resulting 3D model was visualized using a VR headset. After completing the segmentation procedure, ten cases were evaluated by a panel of six surgeons, including both senior and resident physicians from ENT and oculoplastic specialties. Results The dataset under examination comprised images from 10 preoperative CT scans of the orbits of patients eligible for Endo-DCR. When evaluating the CT using the VR tool, in 73.3% of the cases ENT surgeons were right about the side of pathology, while only 43.3% ophthalmologists were right (chi-square, p = .018). In 72.8% of the cases ENT surgeons were evaluated right that there is a septum deviation, while only in 47.2% of the cases the ophthalmologists were right (chi-square, p = .094). When evaluating the CT using the VR tool, in 60% of the cases consultants were right about the pathology, while 57.7% of the residents were right (chi-square, p = .853). In 81.7% of the cases consultants were evaluated right that there is a septum deviation, while only in 58.3% of the cases the ophthalmologists were right (chi-square, p = .198). Discussion ENT surgeons, as well as consultants, interpreted the CT better than the ophthalmologists and residents. Surprisingly, the VR system did not help them to interpret the CT better. Further, more extensive studies should be done to build a VR system that assists in the correct interpretation of the preoperative CT before DCR surgery as well as during DCR surgery.

The Impact of Heat-Not-Burn, E-Cigarettes, and Cigarettes on Small Airway Function.

E-cigarettes and heated tobacco products (HTPs) are gaining worldwide significance. The tobacco industry is promoting these products as healthier alternatives to conventional cigarettes. In this four-arm crossover study, we examined the acute effects of cigarette smoking, vaping IQOS, or vaping e-cigarettes (with or without nicotine) on hemodynamics, arterial stiffness, and small airways. Twenty subjects (10 male, 10 female), all occasional smokers, completed each study arm. There was at least a 48h washout period before each test day. Arterial stiffness and peripheral and central hemodynamics were assessed using Mobil-O-Graph™ (I.E.M., Germany), whereas tremoFlo® c-100 (Thoracic Medical Systems Inc) was used to evaluate the effects on the small airways and resistance. Cigarettes, IQOS, e-cigarettes containing nicotine, and nicotine-free e-cigarettes had similar effects on peripheral and central hemodynamics as well as on arterial stiffness. We observed a significant increase in all parameters. However, only nicotine-containing products lead to increased bronchial obstruction, higher reactance, and a higher tidal volume. Therefore, we concluded that cigarettes, IQOS, and e-cigarettes have similar effects on hemodynamics. No differences were observed between the nicotine-containing and nicotine-free e-cigarettes. All nicotine-containing products also influence small airways. These findings suggest that e-cigarettes and HTPs are not healthier alternatives than conventional cigarettes.

Development of an FRα Companion Diagnostic Immunohistochemical Assay for Mirvetuximab Soravtansine.

Folate receptor-α (FRα, encoded by the FOLR1 gene) is overexpressed in several solid tumor types, including epithelial ovarian cancer (EOC), making it an attractive biomarker and target for FRα-based therapy in ovarian cancer. To describe the development, analytic verification, and clinical performance of the VENTANA FOLR1 Assay (Ventana Medical Systems Inc) in EOC. We used industry standard studies to establish the analytic verification of the VENTANA FOLR1 Assay. Furthermore, the VENTANA FOLR1 Assay was used in the ImmunoGen Inc-sponsored SORAYA study to select patients for treatment with mirvetuximab soravtansine (MIRV) in platinum-resistant EOC. The VENTANA FOLR1 Assay is highly reproducible, demonstrated by a greater than 98% overall percent agreement (OPA) for repeatability and intermediate precision studies, greater than 93% OPA for interreader and greater than 96% for intrareader studies, and greater than 90% OPA across all observations in the interlaboratory reproducibility study. The performance of the VENTANA FOLR1 Assay in the SORAYA study was evaluated by the overall staining acceptability rate, which was calculated using the number of patient specimens that were tested with the VENTANA FOLR1 Assay that had an evaluable result. In the SORAYA trial, data in patients who received MIRV demonstrated clinically meaningful efficacy, and the overall staining acceptability rate of the assay was 98.4%, demonstrating that the VENTANA FOLR1 Assay is safe and effective for selecting patients who may benefit from MIRV. Together, these data showed that the assay is highly reliable, consistently producing evaluable results in the clinical setting. The VENTANA FOLR1 Assay is a robust and reproducible assay for detecting FRα expression and identifying a patient population that derived clinically meaningful benefit from MIRV in the SORAYA study.

The Role of AI in Serious Games and Gamification for Health: Scoping Review.

Artificial intelligence (AI) and game-based methods such as serious games or gamification are both emerging technologies and methodologies in health care. The merging of the two could provide greater advantages, particularly in the field of therapeutic interventions in medicine. This scoping review sought to generate an overview of the currently existing literature on the connection of AI and game-based approaches in health care. The primary objectives were to cluster studies by disease and health topic addressed, level of care, and AI or games technology. For this scoping review, the databases PubMed, Scopus, IEEE Xplore, Cochrane Library, and PubPsych were comprehensively searched on February 2, 2022. Two independent authors conducted the screening process using Rayyan software (Rayyan Systems Inc). Only original studies published in English since 1992 were eligible for inclusion. The studies had to involve aspects of therapy or education in medicine and the use of AI in combination with game-based approaches. Each publication was coded for basic characteristics, including the population, intervention, comparison, and outcomes (PICO) criteria; the level of evidence; the disease and health issue; the level of care; the game variant; the AI technology; and the function type. Inductive coding was used to identify the patterns, themes, and categories in the data. Individual codings were analyzed and summarized narratively. A total of 16 papers met all inclusion criteria. Most of the studies (10/16, 63%) were conducted in disease rehabilitation, tackling motion impairment (eg, after stroke or trauma). Another cluster of studies (3/16, 19%) was found in the detection and rehabilitation of cognitive impairment. Machine learning was the main AI technology applied and serious games the main game-based approach used. However, direct interaction between the technologies occurred only in 3 (19%) of the 16 studies. The included studies all show very limited quality evidence. From the patients' and healthy individuals' perspective, generally high usability, motivation, and satisfaction were found. The review shows limited quality of evidence for the combination of AI and games in health care. Most of the included studies were nonrandomized pilot studies with few participants (14/16, 88%). This leads to a high risk for a range of biases and limits overall conclusions. However, the first results present a broad scope of possible applications, especially in motion and cognitive impairment, as well as positive perceptions by patients. In future, the development of adaptive game designs with direct interaction between AI and games seems promising and should be a topic for future reviews.

Application of Industrial-Scale Lithium Sulphate Electrolysis in Battery Recycling

As the world charges towards electrification and sustainable transportation, it is critical that the entire supply chain is equally sustainable. Industrial processes must be tailored towards circular processes in which emissions and effluents to the environment are minimized, if not eliminated altogether. When it comes to the production of battery grade lithium hydroxide monohydrate, a critical component of lithium ion batteries (LIBs), and the recovery of the lithium in spent LIBs. NORAM Electrolysis Systems Inc (NESI) has developed electrochemical technologies in which effluents are greatly reduced.NESI has developed a flexible, multi-compartment industrial electrolyser for salt splitting (NORSCAND®) applications including electrolysis of lithium sulphate to produce battery-grade lithium hydroxide (LHM). This electrolysis step can be used for the initial production of LHM or for recovering the LHM from recycling LIBs. In either case sulphuric acid is a by-product of the electrolysis process and it can then be recycled for dissolution of black mass in battery recycling processes or for e.g. SX regeneration. In both cases the incorporation of electrolysis in the flowsheet eliminates effluent streams.This presentation will outline the product quality and environmental benefits of electrolysis applied as part of a battery recycling flowsheet. It will outline the approach to electrolyser scale-up and present test and performance data from industrial-scale application. Figure 1

Functional state of the endothelium in men after mine-explosive injury during the war in Ukraine

Mine-explosive trauma (MET) is the most common trauma type and one of the main disability causes of the able-bodied contingent. Among the mechanisms of the cardiovascular and cerebrovascular disorders development after MET, endothelial dysfunction (ED) plays an important role. The study aims - to assess the functional state of the microvessels and large arteries endothelium in men after a mine-explosive injury. Materials and methods: the functional state of the skin microvessels endothelium was determined using a two-channel laser Doppler flowmeter BLF-21D "Transonic Systems Inc" (USA) during the test with the creation of reactive hyperemia. The function of the large arteries endothelium was determined using the D.S. Celermajer test, with post-occlusion reactive hyperemia according to the generally accepted method on the Nemio XG device, SSA-580A (Toshiba) with a high-frequency linear sensor with a central frequency of 7 MHz. We examined men with mild MET (average age 37.7 ± 1.5 years). The control group was represented by 43 practically healthy men without MET (average age 41.8 ± 2.1 years). Results: dysfunction of the microvessels endothelium was found in most persons with MET (69.1%), compared to men without MET (41.9%). Dysfunction of the large vessels endothelium was found in 40.4% of examined persons with MET. Persons with MET have a combination of large and small vessel endothelial dysfunction in 23.4% of cases, at the same time persons without MET have a higher proportion of isolated microvessel endothelial dysfunction (34.9%). Conclusions: men with MET often have arterial endothelial dysfunction with microvascular endothelial dysfunction together, whereas men without MET have predominantly isolated microvascular endothelial dysfunction. ________________________________________________________________________________________ Keywords: mine-explosive injury; functional state of the endothelium; microcirculation.

Validation of Dual-Color Dual In Situ Hybridization for HER2/neu Gene in Breast Cancer.

Human epidermal growth factor (HER2/neu) gene amplification, a poor prognostic factor in invasive breast cancer, has shown substantial utility as a predictive marker, with significantly improved survival following anti-HER2 therapies like trastuzumab. Dual-color dual in situ hybridization (D-DISH), a recently introduced fully automated assay for HER2/neu evaluation on light microscopy, has several advantages over fluorescence in situ hybridization (FISH). To standardize and validate the D-DISH assay using FISH as the gold standard and assess interobserver reproducibility in interpreting the D-DISH assay. D-DISH was performed using the latest HER2 Dual ISH DNA Probe Cocktail assay (Ventana Medical Systems Inc, Tucson, Arizona) in 148 cases of invasive breast cancer. The same block was used for performing immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody and FISH assay by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe. D-DISH was separately interpreted by 4 pathologists blinded to FISH results. Concordance of 98.65% and a Cohen κ value of 0.97 were observed between FISH and D-DISH. Intraclass correlation coefficient (0.93-0.97) and κ values (0.98-1.0) for interobserver reproducibility showed almost perfect agreement by D-DISH. Interobserver reproducibility was also evaluated for genomic heterogeneity, HER2 group categorization, and polysomy (κ values 0.42-0.74, 0.89-0.93, and 0.98-1.0, respectively). We successfully validated the latest version of D-DISH assay as a substitute for FISH in predicting HER2 gene status with significant interobserver reproducibility, concluding that this D-DISH assay may be introduced in routine diagnostic services as a reflex test to ascertain HER2 gene status.

Caste-ing White Supremacy

This paper examines the landmark 1923 Supreme Court case, United States v. Bhagat Singh Thind, alongside the Hindutva response to a 2020 landmark case, California Department of Fair Employment and Housing v. Cisco Systems Inc. These two cases are in many ways different: while Thind was confronting racial prerequisite laws concerning citizenship, the Hindu right (or Hindutva) is protesting the inclusion of caste in antidiscrimination laws. Yet, reading these together enables us to see how upper-caste South Asians have historically mobilized caste to uphold not only Brahminical, but also white supremacy. While much work on race and caste highlights the parallels between racism and casteism as descent-based discriminations, I illuminate how they intersect, shaping immigrant struggles to establish belonging and rights in the United States. Caste served as a lynchpin for Thind’s case. Thind and his legal team used caste to prove the purity of Thind’s “Aryan blood” and therefore his whiteness and eligibility for citizenship. In doing so, they also reproduced anti-Blackness. Though the Supreme Court rejected Thind’s argument, it retained the idea that caste, race, and blood are linked. Nearly a century later, Hindutva’s response to Cisco appears to want to abolish caste by not naming it. Yet, read alongside the rise of the language of “merit” and “castelessness” in India, and the move to “colorblindness” and model minority racialization in the United States, their “caste-blind” agenda bolsters both Brahminical and white supremacy.

#6235 ELEVATED PLASMA ANGIOPOETIN-2 PREDICT THE NEED FOR DIALYSIS INITIATION IN PATIENTS WITH CKD 4 AND 5 WITHIN TWO YEARS

Abstract Background and Aims Volume status, congestion and endothelial activation/injury were found to play a role in GFR decline and CKD progression. This pilot study aimed to determine whether the plasma markers of endothelial injury and activation as well as markers of fluid overload could serve as independent predictors for dialysis initiation in stable patients with CKD 4 and 5 and preserved EF. Method This prospective study was conducted from March 2019 to March 2022 and enrolled consecutive patients with GFR &amp;lt;30ml/min/1.72 m2 and preserved LVEF. Plasma levels of angiopoietin (Ang)-2, Vascular Endothelial Growth Factor-C (VEGF-C), Vascular Cell Adhesion Molecule-1 (VCAM-1), Copeptin (CPP), beta-trace protein (BTP), brain natriuretic peptide (BNP), cardiac troponin I (cTnI) were measured (Quantikine ELISA;R&amp;D Systems Inc, Minneapolis, MN). Clinical markers of congestion were also recorded: lung US (B-lines), bioimpedance (ECV/ICV), echocardiography with global longitudinal strain (GLS), pulse wave velocity (PWV). Study outcome was need to initiate dialysis during 24-months follow-up. Results We analyzed a total of 105 patients with mean eGFR 21,3 ml/min/1.73m. The median age at enrollment was 52 (+/-14.8) years and 65% of the patients were male; 79% were hypertensive and 24% were diabetic. A positive correlation between concentration of Ang-2 and VCAM-1 and BTP was observed. Ang-2 concentration correlated positively with BNP, TnT, sCr, e/e’, ECV/ICV. Over a follow-up period of 24 months, the deterioration of renal function was observed in 47 patients (58%), 31 (38%) presented stable or ameliorated renal function and 24 on maintenance dialysis formed a control group. In Kaplan-Meier analysis significant impact of Ang-2 on renal survival (Figure) was found. Namely, 72% of patients with Ang-2 concentrations below the median (3.15 ng/ml) survived without dialysis for two years, compared to 42% of those with Ang-2 concentrations above the median. Such impact was not observed for GFR, VCAM, CCP, VEGF-C, BTP. Conclusion Endothelial activation, quantified by plasma levels of Ang-2 may play an important role in GFR decline and need for dialysis initiation in patients with CKD 4 and 5.

Monolithic Power Systems Inc.

Corporate Philanthropy ReportVolume 38, Issue 6 p. 11-11 Corporate Profiles Monolithic Power Systems Inc. First published: 08 May 2023 https://doi.org/10.1002/cprt.31627Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume38, Issue6June 2023Pages 11-11 RelatedInformation

PO-03-013 ELECTRO-ANATOMICAL CHARACTERIZATION OF LEADLESS LEFT BUNDLE BRANCH AREA PACING

Leadless left ventricular (LV) endocardial pacing with the WiSE-CRT System (EBR Systems Inc) is an emerging treatment in the field of cardiac resynchronization therapy (CRT). Whilst the system was designed to provide LV lateral wall endocardial pacing, modifications to the implant technique have recently enabled positioning of the pacing electrode in the LV septum to perform left bundle branch area pacing (LBBAP). The electrical performance of leadless LBBAP is yet to be determined. We aimed to electro-anatomically characterize the biventricular (BiV) activation patterns of leadless LBBAP in patients with heart failure receiving CRT with the WiSE-CRT system. Four patients with the WiSE-CRT System, all with the pacing electrode located in the LV septum, underwent an electrocardiographic imaging (ECGi) study. The following pacing modalities were tested: Right Ventricular Pacing (RVP); BiV pacing (RVP + LV); LV only; and LV only with an electrically optimised atrioventricular delay (AVD) in patients with sinus rhythm. Reconstructed epicardial electrograms from ECGi were used to calculate LV activation time (LVAT-90), RV activation time (RVAT-90), BiV activation time (BIVAT-90), LV dyssynchrony index (LVDI), and BiV dyssynchrony index (BIVDI). For each metric, the percentage improvement compared to RVP was calculated. At the optimal pacing modality, CRT using leadless LV septal endocardial pacing achieved significant improvements in: LVAT-90 (33.9% ± 24.6, p=0.01); RVAT-90 (51.7% ± 24.1, p=0.003); BiVAT-90 (31.3% ± 30.8, p=0.03) and LV-DI (39.7% ± 39.7, p=0.03), see figure. There was individual variability in optimal pacing modality (see table). For 2 patients with sinus rhythm (SR) and left bundle branch block (LBBB), the optimal modality was LV only pacing with optimised AVD. Two patients had AF and complete heart block (CHB). For these cases, BiV pacing achieved the optimal results for 1 patient, whereas LV only pacing performed best for the other. Leadless LV LBBAP endocardial pacing significantly improves ECGi-derived activation metrics at the optimal pacing modality in both patients in SR and AF. For those with underlying SR and LBBB, LBBAP with AVD optimisation may be the optimal modality as this allows RV activation via native conduction. As each patient required a different protocol to achieve the optimal result, personalisation may be important for LV LBBAP.Tabled 1Optimized pacing setting by activation metric (PO-03-013)PatientUnderlying RhythmBiVAT-90LVAT-90RVAT-90LV-DIBiV-DI1AF, CHBLV onlyLV onlyLV onlyLV onlyLV only2SR, LBBBLV with optimized AVD 80msLV with optimized AVD 100msLV with optimized AVD 130msLV with optimized AVD 80msLV with optimized AVD 100ms3AF, CHBBiVLV onlyBiVLV onlyBiV4AF, LBBBLV only with optimized AVD 180msLV only with optimized AVD 160msLV only with optimized AVD 160msLV only with optimized AVD 160msLV only with optimized AVD 160ms Open table in a new tab

Is Thalamic DBS Synergistic With VNS in Drug Resistant Genetic Generalized Epilepsy? (P5-1.001)

<h3>Objective:</h3> To report prolonged seizure freedom and improved quality of life after combining anterior nucleus of the thalamus deep brain stimulation (ANT-DBS) with vagus nerve stimulation (VNS) in a patient with drug resistant genetic generalized epilepsy (GGE). <h3>Background:</h3> Neuromodulation remains at forefront of management in patients with drug-resistant epilepsies though efficacy has been palliative and FDA approved in focal epilepsies. While polytherapy with anti-seizure medications (ASMs) is common, dual neuromodulation has received limited attention. <h3>Design/Methods:</h3> A 32-year-old female patient with drug resistant GGE who failed 10 antiseizure medications underwent video-EEG monitoring. EEG revealed 3–3.5 Hz generalized polyspike-and-wave discharges and generalized paroxysmal fast activity in brief run lasting less than 3 seconds increased during sleep. Seizures were not recorded. VNS model 106 Aspire SR was implanted at age 23 achieving parameters of 1.5 mA, 25 Hz, 250 μs, 14 sec on, 1.1 min off. Despite improvement with seizure reduction, ongoing monthly convulsions resulted in recurrent injuries. The patient subsequently underwent bilateral ANT-DBS placement with inferior most contacts on both sides well-positioned at the junction of the mammillothalamic tracts for monopolar stimulation at 5 V, 145 Hz, and 90 μs. <h3>Results:</h3> Neuro- “modulation” was observed in our patient with VNS following implantation of ANT-DBS by gradual reduction diminishing seizure frequency, intensity, and duration to ultimately become seizure-free for 21 months. Stable doses of Onfi 20 mg po bid and Keppra 1500 mg po bid were continued. After combining ANT-DBS with her incomplete VNS response she married, became employed, and was able to retain driving privileges and lead an independent lifestyle. <h3>Conclusions:</h3> Identifying a subset of patients with GGE responsive to polyneuromodulation promises personalized therapy for those with life-altering effects from generalized seizures. We speculate that the thalamic network connectivity may be modulated by dual ANT-DBS and VNS, leading to targeted neurobiological therapy in some patients with GGE. <b>Disclosure:</b> Dr. Khan has nothing to disclose. Erik Middlebrooks has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Varian Medical Systems Inc. Erik Middlebrooks has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Corp. The institution of Erik Middlebrooks has received research support from Varian Medical Systems Inc. Dr. Freund has nothing to disclose. Sanjeet S. Grewal, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Tatum has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bioserenity. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Defense Law Firm on behalf of a patient with epilepsy with funds donated to the Epilepsy Foundation of America. The institution of Dr. Tatum has received research support from Esai. The institution of Dr. Tatum has received research support from Mayo Clinic. The institution of Dr. Tatum has received research support from Liva Nova. The institution of Dr. Tatum has received research support from Engage Pharmaceuticals. The institution of Dr. Tatum has received research support from Xenon. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Tatum has received publishing royalties from a publication relating to health care.

Protective Effect of APOE-ɛ2 on Cortical Thickness and Volume in a Cerebrovascular Registry (S36.010)

<h3>Objective:</h3> To compare cortical thickness across APOE genotypes, and to assess the potential protective effect of APOE2 on brain cortical thinning and grey matter volume. <h3>Background:</h3> Studies have shown a negative association of APOE-ɛ4 allele with regional cortical thickness and volume. The role of the APOE-ɛ3 allele has been considered neutral in several studies. The protective role of APOE-ɛ2 against cortical thinning has not been well established. <h3>Design/Methods:</h3> From a biomarker cerebrovascular registry, 187 individuals with APOE testing and MRI brain from 2010 to 2020 were included. APOE genotype tested were ɛ2ɛ2, ɛ2ɛ3, ɛ2ɛ4, ɛ3ɛ3, ɛ3ɛ4, ɛ4ɛ4, stratified to APOE-ɛ2 carrier or APOE-ɛ2 non-carrier. Cortical thickness, cortical volume and gray matter volume were estimated on T1-weighted images using FreeSurfer. Measures of brain atrophy were compared across APOE genotypes, and between ɛ2 vs non-ɛ2 allele carriers. Mini-Mental Status Examination (MMSE) were compared between groups. <h3>Results:</h3> In our cohort (n=187), mean age was 60±16 years and 55.4% were female. Of the APOE genotypes, 18.5% were APOE-ɛ2 carriers (ɛ2ɛ2 3, ɛ2ɛ3 33), 81.5% were APOE-ɛ2 non-carriers (ɛ3ɛ3 114, ɛ3ɛ4 43, ɛ4ɛ4 2). Compared to ɛ2 non-carriers, ɛ2 carriers were less likely to have hypertension, diabetes, coronary artery disease, and had higher LDL (p&lt;0.05). Across APOE genotypes, cortex was thickest in ɛ2ɛ2 (2.35 mm) and thinnest in ɛ4ɛ4 (1.92 mm) (p = 0.0137). APOE-ɛ2 carriers had significantly thicker cortex (2.13 mm vs 1.96 mm, p=0.001), larger cortical volume (313.26 cm3 vs 266.09 cm3, p=&lt;0.001) and grey matter volumes (459.93 cm3 vs 411.01 cm3, p=0.001), compared to ɛ2 non-carriers. There was no difference in MMSE between ɛ2carriers vs non-carriers (24.4 vs 25.6, p=0.316). <h3>Conclusions:</h3> Our study suggested a protective effect of APOE-ɛ2 allele against cortical thinning and grey matter volume loss. Future study may examine the effect of APOE-ɛ2 on brain resilience after brain injury such as stroke. <b>Disclosure:</b> Mr. Youssef has nothing to disclose. Mr. Mateti has nothing to disclose. Erik Middlebrooks has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Varian Medical Systems Inc. Erik Middlebrooks has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Corp. The institution of Erik Middlebrooks has received research support from Varian Medical Systems Inc. The institution of Dr. Taner has received research support from NIH. The institution of Dr. Meschia has received research support from NINDS. The institution of Dr. Meschia has received research support from NINDS. Dr. Lin has nothing to disclose.

THE CONTRALATERAL LIMB IS NOT AN ADEQUATE REHABILITATION GOAL FOR ASSESSING MUSCLE FUNCTION IN AN ANTERIOR CRUCIATE LIGAMENT-INJURED PAEDIATRIC POPULATION

To investigate changes in quadriceps and hamstrings muscle groups during sustained isokinetic knee flexion and extension.125 paediatric participants (45 males and 80 females, mean age 14.2 years) were divided into two groups: participants with a confirmed ACL tear (ACLi, n = 64), and puberty- and activity-level matched control participants with no prior history of knee injuries (CON, n = 61). Participants completed a series of 44 repetitions of isokinetic knee flexion and extension at 90 deg/ sec using a Biodex dynamometer (Biodex Medical Systems Inc, Shirley, New York). Surface EMG sensors (Delsys Incorporated, Natick, MA) simultaneously recorded the quadriceps and hamstring activations. Muscle function was assessed as the change in quadriceps activation and extension torque were calculated using the percent difference between the mean of the first five trials, and the mean of the last five trials.ACLi participants had significantly higher percent change in quadriceps activation for both healthy and injured legs, in comparison to CON dominant leg. As such, the healthy leg of the ACLi participants is activating significantly more than their health matched controls, while also demonstrating reduced muscular endurance (less torque in later repetitions). Therefore, we conclude that the non-injured limb of the ACLi participant is not performing as a healthy limb. Since return to activity clearance following ACLi implies return to sport against age- and activity matched opponents, clearing young athletes based on the non-injured contralateral limb may put them at greater risk of reinjury.

Focus on lasers, imaging, microscopy, and nanoscience

Focus on lasers, imaging, microscopy, and nanoscience

In Vitro Drug Studies of Inhibiting MDSC to Improve Efficacy of ICI (immune check point inhibitor) Therapy in Ph(-) myeloproliferative Neoplasm

Although there has been much progress in the use of immune check-point inhibitor (ICI) therapy to treat cancers, very few studies have been published regarding the ICI therapy in Ph(-) myeloproliferative neoplasm (MPN). One clinical trial by Mascarenhas and his associates (ASH annual meeting 2020) in treating nine myelofibrosis patients with pembrolizumab was a anegative trial with no patients responded. Recent studies suggest a leading role for MDSCs in the immunosuppressive tumor micro-environments (TME) which could be the main cause of therapeutic resistance to ICI therapy. Therefore, we perform in vitro experiments to test some of potential drug to inhibit MDSC which may be added to the ICI therapy for future clinical ICI therapy in MPN. Material & Methods: 1) in vitro culture for MDSC formation. Peripheral blood mononuclear cells (PBMC) were isolated from patients with ph(-) MPN by Ficoll Hypaque (GE Healthcare) density gradient centrifugation. Monocytes were isolated using CD14 MicroBeads (Miltenyi Biotec) and cultured in RPMI1640 media supplemented with 10% heat- inactivated FBS and 10 ng/mL IL-6 and GM-CSF (R&D Systems Inc) for 5 days. 2) Drug treatment. Where indicated, monocytes were treated with 0.01% DMSO or 1 umol/L each of Ibrutinib (in 0.01% DMSO), Ruxolitinib (in 0.01% DMSO). Lenalidomide (in 0.01% DMSO) for 1 hour every day during the MDSC cultures. 3) Flow cytometry: Cultured MDSC cells were subject for flow cytometric assessment on BD Accuri C6 flow cytometer. Monocytic MDCS was determined as HLA-DRdim/- and CD14+; guanulocytic MDCS as HLA-DRdim/-, CD14-, and CD33+, (BD Biosciences Inc). The flow data were processed using FlowJo vX. 4) T cell proliferation assay. T cells were isolated from a T4 or T8 isolation kits then T cells were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE; Life Technologies). T cells were nonspecifically activated with anti-CD3/CD28 beads (Life Technologies) and cocultured at 1:1 ratios of T cells to the MDSC obtained from in vitro culture, in the presence of 10 ng/mL IL2 (Invitrogen). After 3 days, T-cell proliferation levels (CFSE) in gated CD4+ and CD8+ cells was assessed respectively by flow cytometry. The flow data were processed using FlowJo vX. Results: After 5 days cultures, Fig 1a ,b, c, shows Ruxolitinib, Ibrutinib, Lenalidomide significantly inhibits M-MDSC formation presented as (mean + SE ( % of DMSO )) of 79.72 + 4.66 ( n=27) , 73.19 + 4.71 (n=31), and 72.48 + 5.89 (n=20)respectively; Inhibits G-MDSC as of 77.82 + 5.66 (n=27) ,66.34 + 5.79 (n=31), (73.59 + 7.03) (n=20) respectively. Fig 2 showed CFSE levels in proliferated CD4+ (Fig. 2 A-D) and CD8+ (Fig.2 E-H) cells in a representative MF patient. Conclusion: Ibrutinib, Ruxolitinib, Lenalidomide significantly inhibits MDSC formation in vitro in patients with MPN and improves T cell function. A further clinical trial to evaluate the combination of ICI therapy with MDSC inhibitor such as Ibrutinib , Ruxolitinib or Lenalidomide may be worthwhile in treating patients with Myelofibrosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Genotyping and Cytology Triage of High-Risk HPV DNA Positive Women for Detection of Cervical High-Grade Lesions.

A demonstration project of primary human papillomavirus (HPV) testing was initiated in 2011 among more than 23,000 women attending routine cervical cancer screening. We examined the additional diagnostic performance of HPV genotyping for detecting disease in women with abnormal cytology. Women aged 30 to 65 years were originally screened for HPV using Hybrid Capture II test. Women with positive results were triaged using conventional cytology, and those with atypical squamous cells of undetermined significance or worse (≥ASC-US) were referred to colposcopy. We retrospectively genotyped (Roche cobas 4800 HPV system [Roche Molecular Systems Inc, Pleasanton, CA]) cervical specimens that were HPV + with Hybrid Capture II test and extracted women's medical history postbaseline screening. We calculated positive predictive values (PPVs) and 95% confidence intervals (CIs) of triage tests to detect histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2 + ) within the first year of follow-up among women positive for HPV16, HPV18, and HPV16 and/or HPV18 as well as among those negative for HPVs 16 and 18. Of 1,396 HPV-positive women, 1,092 (78%) were classified as normal, 136 (10%) had CIN1, 80 (6%) had CIN2, 81 (6%) had CIN3, and 7 women had cancer throughout the entire follow-up period. Seventy CIN2 + cases were detected within the first year of follow-up. The PPV for detecting CIN2 + was 20.9% (63/239; 95% CI = 16.4-25.9) for ASC-US + cytology. In women with ASC-US + , PPVs were 31.2% (24/77; 95% CI = 21.1-42.7) for HPV16 + , 27.8% (5/18; 95% CI = 9.7-53.5) for HPV18 + , 30.8% (28/91; 95% CI = 21.5-41.3) for HPV16 + and/or HPV18 + women, and 16.6% (35/211; 95% CI = 11.8-22.3) in women testing negative for HPVs 16 and 18. Partial genotyping as an additional triage strategy to cytology can markedly improve clinical diagnostic performance.

Clinical validation of a smartphone application for automated wound measurement in patients with venous leg ulcers.

Chronic wounds are associated with significant clinical, economic and quality-of-life burden. Despite the variety of wound imaging systems available in the market for wound assessment and surveillance, few are clinically validated among patients of Asian ethnicity. We aimed to clinically validate the accuracy of a smartphone wound application (Tissue Analytics [TA], Net Health Systems Inc, Florida, USA), versus conventional wound measurements (visual approximation and paper rulers), in patients of Asian ethnicity with venous leg ulcers (VLU). A prospective cohort study of patients presenting with VLU to a specialist wound nurse clinic over a 5-week duration was conducted. Each patient received seven wound measurements: one by a trained wound nurse clinician, and three separate wound measurements using TA on each of the iOS and Android operating systems. Inter-rater and intra-rater reliability between clinical and TA-based measurements were analysed using intra-class correlation statistics, with values of <0.5, 0.5 to 0.75, 0.75 to 0.9, and >0.9 indicating poor, moderate, good and excellent reliability, respectively. 82 patients (51% males), with a mean age at 65.8 years, completed the 5-week study duration. 25 (30%) had underlying diabetes mellitus. Chinese, Malay and Indian ethnicity comprised 68%, 12% and 11%, respectively. The VLU healed in 26 (32%) of patients within the study period. In total, 358 wound episodes with 2334 wound images were analysed. Inter-rater reliability for length, width and area between wound nurse measurements and TA application measurements was good (range 0.799-0.919, P < 0.001). Separate measurements of intra-rater reliability for length, width and area within the iOS or Android systems were excellent (range 0.967-0.985 and range 0.977-0.984 respectively, P < 0.001). Inter-rater reliability between TA used on the iOS and Android systems was also excellent (0.987-0.989, P < 0.001). Tissue Analytics, a smartphone wound application, is a useful adjunct for wound assessment and surveillance in VLU patients of Asian ethnicity.