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Background To evaluate the long-term effects of combined endoscopic cyclophotocoagulation and phacoemulsification (phaco) versus phacoemulsification alone on intraocular pressure control and medication reliance in the treatment of mild to moderate glaucoma. Design Retrospective chart review in private practice setting by glaucoma fellowship trained surgeons. Participants A total of 261 eyes in the combined phaco-endoscopic cyclophotocoagulation group with 52 eyes in the phaco-alone group. Methods Comparison of phaco-endoscopic cyclophotocoagulation with phaco alone over 36 months. Main Outcome Measures Full and qualified success cumulative survival, intraocular pressure and medication reliance 6–36 months compared with baseline. Full success was defined as minimum 20% intraocular pressure reduction with a decrease of at least one ocular hypertensive medication. Qualified success was defined as intraocular pressure no higher than baseline with a decrease of at least one ocular hypertensive medication. Results At 36 months, mean intraocular pressure in the combined phaco-endoscopic cyclophotocoagulation group was 14.6 mmHg, whereas the phaco-alone group was 15.5 mmHg (P = 0.34). Mean medication reliance in the combined phaco-endoscopic cyclophotocoagulation group was 0.2 medications, whereas the phaco-alone group was 1.2 (P

Cubic Li7La3Zr2O12 (LLZO) garnets have attracted lots of attention in previous years as they show promising properties as a solid electrolyte for Solid-state Li batteries (SSLB), such as high ionic conductivity in the range of 1 mS cm-1 and high electrochemical stability up to 6 V.1 Despite of these promising prerequisites, its implementation in SSLB leads to high interfacial resistance that limits its current use in such devices. This high interface resistance relates to the required high temperature treatment to form a good contact between LLZO and, e.g., LiCoO2.2 It is known that this is related to the formation of interdiffusion layers that imped the ionic transport across the interface. Herein, we present that Co does not only lead to the formation of resistive interlayers, such as La2CoO4, but also leads to the incorporation of Co into the garnet lattice. Since, Co is a transition metal its incorporation could change, e.g., (i) the electronic conductivity, being suggested to play a critical role for dendrite formation within the garnet, and (ii) the band gap, hence, the electrochemical stability. Moreover, we also observed, that La diffuses into LiCoO2, which potentially changes the electrochemical properties of the cathode material as well.3 , 4 We mirrored the properties of the interface by incorporating Co from LiCoO2 powder into Czochralski-grown Li6.4Ga0.2La3Zr2O12 single crystals over the gas phase at high temperature. Interestingly, the color changed from yellow, orange to dark blue depending on the heating history. Thereafter we applied a wide spectrum of techniques, such as SC XRD, UV-VIS, TOF-SIMS, 57Emission Mößbauer spectroscopy, DFT/AIMD simulations, impedance spectroscopy and cyclic voltammetry to understand the role of Co in LLZO. For example, we found that the band gap decreases up to 2 eV by the incorporation of 0.1 Co per formula unit (pfu) and a La deficit of 0.12 pfu. This change in the band gap manifests itself in a decreased electrochemical stability of LLZO indicated by an oxidative peak below 4 V as observed in the CV measurement. Moreover, we found that the incorporation of Co leads to a significant change in the Li ion transport. The impedance analysis revealed a low activated (E a = 0.43 eV) process at temperatures between -100 °C and 110 °C and another highly activated (E a = 0.7 eV) diffusion process predominantly present at temperatures > 160 °C. By extrapolating the highly activated process to room temperature, an ionic conductivity σ = 2.91 x 10-6 S cm-1 could be calculated which is about two orders of magnitude lower than values found for pristine LLZO. References: Hofstetter, K. et al. Electrochemical Stability of Garnet-Type Li7La2.75Ca0.25Zr1.75Nb0.25O12 with and without Atomic Layer Deposited-Al2O3 under CO2 and Humidity . J. Electrochem. Soc. 166, A1844–A1852 (2019). Park, K. et al. Electrochemical Nature of the Cathode Interface for a Solid-State Lithium-Ion Battery: Interface between LiCoO2 and Garnet-Li7La3Zr2O12. Chem. Mater. 28, 8051–8059 (2016). Kim, K. H. et al. Characterization of the interface between LiCoO2 and Li7La3Zr2O12 in an all-solid-state rechargeable lithium battery. J. Power Sources 196, 764–767 (2011). Han, F. et al. High electronic conductivity as the origin of lithium dendrite formation within solid electrolytes. Nat. Energy 4, 187–196 (2019).

e21589 Background: Although cure rates are high for cSCC, an estimated 2-6% of cSCC patients will develop regional/distant metastasis and due to high incidence, mortality levels are similar to melanoma. ART is used for high-risk cSCC (HRcSCC) patients to reduce the risk of recurrence and/or metastasis, but guidelines are confounding and lack clarity regarding which patients may benefit from ART. The 40-GEP test has been validated to predict a patient’s risk for regional/distant metastasis: Class 1-low; Class 2A-moderate; and Class 2B-high risk for metastasis. We hypothesize that a 40-GEP Class result could help further stratify patient risk within an ART-eligible population. Methods: Using criteria within NCCN guidelines and other high-risk features to determine ART-eligibility, 86 cases of the 420 HRcSCC patients having known outcomes from the 40-GEP multicenter validation cohort were identified. Criteria included patients presenting with two or more risk factors: tumor diameter ≥2 cm, poor differentiation, perineural invasion ≥0.1 mm, invasion beyond subcutaneous fat, and immunosuppression. Kaplan-Meier survival analysis and log rank test were used to assess metastasis free survival (MFS). Univariate Cox regression compared metastasis rates between 40-GEP Class results. Results: The 3-year MFS rate for the overall ART-eligible cohort was 65% (n = 86, 32 events, 95% CI: 56 – 76%). The 40-GEP demonstrated statistically significant stratification of risk with MFS rates of 79%, 63% and 33% for Class 1, Class 2A and Class 2B, respectively (p = 0.005). Cox regression was significant between Class 1 and Class 2B 40-GEP results (p = 0.002), with Class 2B having a 4.59-fold increase in metastases. 40% (34/86) of the cohort received a Class 1 result, highlighting HRcSCC patients who may be considered for reduction or avoidance of ART. In 14% (12/86) of cases with a Class 2B result, 2 of 3 patients went on to have metastasis and thus may be appropriate for more aggressive intervention in the setting of a clinical trial. Those cases meeting eligibility for 40-GEP testing but not ART-criteria (n = 334) and with a Class 2B result (n = 11) had a 64% MFS rate, similar to the ART-eligible population. Conclusions: The 40-GEP test stratifies a patient’s risk of regional and/or distant metastasis in patients for whom ART is typically considered. Incorporation of 40-GEP testing may help guide patient management decisions in HRcSCC by potentially decreasing over-treatment of patients with HRcSCC and identifying patients with otherwise lower risk disease who may benefit from ART and/or other adjunctive therapies.

Highlights • Acute cardiac injury (elevated Troponin) ranges from 8 to 28% in COVID-19 patients. • Standard overt cardiac dysfunction in TTE among COVID-19 patients is uncommon. • However, signs of subclinical myocardial dysfunction by GLS is prevalent., Background The incidence of acute cardiac injury in COVID-19 patients is very often subclinical and can be detected by cardiac magnetic resonance imaging. The aim of this study was to assess if subclinical myocardial dysfunction could be identified using left ventricular global longitudinal strain (LV-GLS) in patients hospitalized with COVID-19. Methods We performed a search of COVID-19 patients admitted to our institution from January 1st, 2020 to June 8th, 2020, which revealed 589 patients (mean age = 66 ± 18, male = 56%). All available 60 transthoracic echocardiograms (TTE) were reviewed and off-line assessment of LV-GLS was performed in 40 studies that had sufficient quality images and the views required to calculate LV-GLS. We also analyzed electrocardiograms and laboratory findings including inflammatory markers, Troponin-I, and B-type natriuretic peptide (BNP). Results Of 589 patients admitted with COVID-19 during our study period, 60 (10.1%) underwent TTE during hospitalization. Findings consistent with overt myocardial involvement included reduced ejection fraction (23%), wall motion abnormalities (22%), low stroke volume (82%) and increased LV wall thickness (45%). LV-GLS analysis was available for 40 patients and was abnormal in 32 patients (80%). All patients with LV dysfunction had elevated cardiac enzymes and positive inflammatory biomarkers. Conclusions Subclinical myocardial dysfunction as measured via reduced LV-GLS is frequent, occurring in 80% of patients hospitalized with COVID-19, while prevalent LV function parameters such as reduced EF and wall motion abnormalities were less frequent findings. The mechanism of cardiac injury in COVID-19 infection is the subject of ongoing research.

Historically, administration of dacarbazine to sarcoma patients was limited by frequent treat-ment-related nausea/vomiting and neutropenia. These toxicities are now largely preventable with contemporary antiemetics and growth factor support. In this single-arm, phase II study, dacarbazine 850 mg/m2 was given on day 1 of each 3-week cycle until disease progression or intolerance with prophylactic serotonin-3 receptor, neurokinin-1 antagonists, corticosteroids, and pegfilgrastim. Coprimary endpoints included clinical benefit rate (CBR), and any grade of nausea/vomiting and/or grade 3–4 neutropenia. With a sample size of 80 patients, >24 patients with clinical benefit would indicate that the CBR exceeds the historical (

Technical advances in CT have enabled implementation of dual-energy CT into routine clinical practice. By acquiring images at two different energy spectra, dual-energy CT enables material decomposition, allowing generation of material- and energy-specific images. Material-specific images include virtual nonenhanced images and iodine-specific images (iodine maps). Energy-specific images include virtual monoenergetic images. The reconstructed images can provide unique qualitative and quantitative information about tissue composition and contrast media distribution. In thoracic oncologic imaging, dual-energy CT provides advantages in characterization of thoracic malignancies and lung nodules, determination of extent of disease, and assessment of response to therapy. An especially important feature in children is that dual-energy CT does not come at a higher radiation exposure. Keywords: CT, CT-Quantitative, Lung, Mediastinum, Neoplasms-Primary, Pediatrics, Thorax, Treatment Effects © RSNA, 2021

Patient: Male, 69 Final Diagnosis: Coronary artery disease Symptoms: Angina pectoris Medication: Aspirin Clinical Procedure: Coronary artery bypass surgery Specialty: Cardiology Objective: Unusual clinical course Background: A preponderance of evidence supports short-term aspirin usage to reduce transiently increased cardiovascular risk in clinical conditions that promote acute myocardial ischemia. Case Report: We report on the case of a 69-year-old male of Muslim Indian heritage with multiple cardiovascular risk factors who experienced the onset of angina pectoris while fasting for Ramadan for more than 16 hours daily for 30 days in July 2015. While symptom free for 2 months on medical management after ending his fast, he underwent quadruple coronary artery bypass surgery for severe 4-vessel disease following an acute anterior myocardial infarction. A percutaneous coronary intervention with stent placement was subsequently required for persistent myocardial ischemia on stress-MIBI testing due to occlusion of the graft to left anterior descending artery. Presently asymptomatic, he decided to forgo fasting for Ramadan in June 2016. Conclusions: Based on this case, measures for primary cardiovascular prevention among the 1.2 billion susceptible males at similar high short-term cardiac risk while fasting for Ramadan are proposed. The value of aspirin for attenuating high short-term cardiovascular risk in clinical conditions conferring transient inflammatory stress is considered. Low-dose aspirin usage at evening meals while fasting for Ramadan is prudent for primary cardiovascular protection of males who may have non-obstructive coronary atherosclerosis to mitigate the risk for rupture of potentially vulnerable plaques. Based in part on conclusive evidence for protection of middle-aged males from first myocardial infarction in a randomized prospective primary prevention trial, this measure is concordant with recommendations from sub-specialty societies for primary cardiovascular prevention for persons at above-average risk demonstrated by validated biomarkers and from the United States Preventive Services Task Force.

A hallmark of insect societies is a division of labor among workers specializing in different tasks. In bumblebees the division of labor is related to body size; relatively small workers are more likely to stay inside the nest and tend ("nurse") brood, whereas their larger sisters are more likely to forage. Despite their ecological and economic importance, very little is known about the endocrine regulation of division of labor in bumblebees. We studied the influence of juvenile hormone (JH) on task performance in the bumblebee Bombus terrestris. We first used a radioimmunoassay to measure circulating JH titers in workers specializing in nursing and foraging activities. Next, we developed new protocols for manipulating JH titers by combining a size-adjusted topical treatment with the allatotoxin Precocene-I and replacement therapy with JH-III. Finally, we used this protocol to test the influence of JH on task performance. JH levels were either similar for nurses and foragers (three colonies), or higher in nurses (two colonies). Nurses had better developed ovaries and JH levels were typically positively correlated with ovarian state. Manipulation of JH titers influenced ovarian development and wax secretion, consistent with earlier allatectomy studies. These manipulations however, did not affect nursing or foraging activity, or the likelihood to specialize in nursing or foraging activity. These findings contrast with honeybees in which JH influences age-related division of labor but not adult female fertility. Thus, the evolution of complex societies in bees was associated with modifications in the way JH influences social behavior.

At the Q Group (the Institute for Quantitative Research in Finance) Spring Seminar, held 17–20 April 2016, Martin Leibowitz moderated a discussion of the important issues in finance by panelists Andrew W. Lo, Robert C. Merton, Stephen A. Ross, and Jeremy Siegel.

Background Evidence suggests a relationship between glenoid retroversion and posterior instability, but no literature exists comparing glenoid version referencing the scapular body versus the endosteal vault. This study evaluated glenoid version and its relationship to unidirectional instability and labral tears. Methods Glenoid version in patients with unidirectional instability or labral tears was measured with magnetic resonance imaging by either the Friedman method or the Poon and Ting method. Analyses of variance followed by independent t tests were used to compare 3 groups: anterior instability or labral tears (anterior pathology group, n = 33); posterior instability or labral tears (posterior pathology group, n = 34); and stable controls (n = 30). The referencing error for 2-dimensional axial images was evaluated for variance by imaging facility. Interobserver and intraobserver reliability scores were calculated. Results With the Friedman method, the posterior pathology group (−9°) was more retroverted than the control group (−4°) ( P = .0005) and the anterior pathology group (−5°) ( P = .0104) but there was no difference between the control group and anterior pathology group ( P = .38). The referencing error in the sagittal plane averaged 23° and varied by facility ( P = .0365). The coronal-plane error averaged 1° and did not vary by facility ( P = .7180). Intraclass correlation coefficient scores showed good to excellent intrarater and inter-rater reliability. Conclusion The posterior pathology group had 5° more retroversion than controls using the Friedman method. Glenoid version using the Poon and Ting method or the Friedman method did not predict anterior instability or labral tears. Axial magnetic resonance images were constructed with a referencing error in the sagittal plane that varied by magnetic resonance imaging facility and has implications for improving 2-dimensional axial imaging protocols.

Metal-organic frameworks (MOFs) are an emerging class of porous, crystalline materials with potential application as hydrogen storage media in fuel cell vehicles. Unlike lower capacity adsorbents such as zeolites and carbons, some MOFs are expected to degrade due to attack by impurities present in the hydrogen fuel stream. Hydrogen intended for use in fuel cell vehicles should satisfy purity standards, such as those outlined in SAE J2719. This standard limits the concentration of certain species in the fuel stream based primarily on their deleterious effects on PEM fuel cells. However, the impact of these contaminants on MOFs is mostly unknown. In the present study MOF-5 is adopted as a prototypical moisture-sensitive hydrogen storage material. Five “impure” gas mixtures were prepared by introducing low-to-moderate levels (i.e., up to ∼200 times greater than the J2719 limit) of selected contaminants (NH3, H2S, HCl, H2O, CO, CO2, CH4, O2, N2, and He) to pure hydrogen gas. Subsequently, MOF-5 was exposed to these mixtures over hundreds of adsorption/desorption pressure-swing cycles and for extended periods of static exposure. The impact of exposure was assessed by periodically measuring the hydrogen storage capacity of an exposed sample. Hydrogen chloride was observed to be the only impurity that yielded a measurable, albeit small, decrease in hydrogen capacity; no change in H2 uptake was observed for the other impurities. Post-cycling and post-storage MOF-5 samples were also analyzed using infrared spectroscopy and x-ray diffraction. These analyses reveal slight changes in the spectra for those samples exposed to HCl and NH3 compared to the pristine material. These measurements suggest that MOF-5 – and likely many other MOFs – exhibit sufficient robustness to withstand prolonged exposure to ‘off-spec’ hydrogen fuel.

Robert Shiller’s cyclically adjusted price–earnings ratio, or CAPE ratio, has served as one of the best forecasting models for long-term future stock returns. But recent forecasts of future equity returns using the CAPE ratio may be overpessimistic because of changes in the computation of GAAP earnings (e.g., “mark-to-market” accounting) that are used in the Shiller CAPE model. When consistent earnings data, such as NIPA (national income and product account) after-tax corporate profits, are substituted for GAAP earnings, the forecasting ability of the CAPE model improves and forecasts of US equity returns increase significantly.

Schizophrenia (SCZ) is a disorder characterized by positive symptoms (hallucinations, delusions), negative symptoms (blunted affect, alogia, reduced sociability, and anhedonia), as well as persistent cognitive deficits (memory, concentration, and learning). While the biology underlying subjective experiences is difficult to study, abnormalities in electroencephalographic (EEG) measures offer a means to dissect potential circuit and cellular changes in brain function. EEG is indispensable for studying cerebral information processing due to the introduction of techniques for the decomposition of event-related activity into its frequency components. Specifically, brain activity in the gamma frequency range (30-80Hz) is thought to underlie cognitive function and may be used as an endophenotype to aid in diagnosis and treatment of SCZ. In this review we address evidence indicating that there is increased resting-state gamma power in SCZ. We address how modeling this aspect of the illness in animals may help treatment development as well as providing insights into the etiology of SCZ.

Mitral regurgitation (MR) is a common valvular disorder that has important health and economic consequences. Standardized guidelines exist regarding when and in whom to perform mitral valve surgery, but little information is available regarding medical treatment of MR. Many patients with moderate or severe MR do not meet criteria for surgery or are deemed to be at high risk for surgical therapy. We reviewed the available published data on medical therapy in the treatment of patients with primary MR. b-blockers and renin-angiotensin-aldosterone system inhibitors had the strongest supporting evidence for providing beneficial effects. b-blockers appear to lessen MR, prevent deterioration of left ventricular function, and improve survival in asymptomatic patients with moderate to severe primary MR. Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy reduces MR, especially in asymptomatic patients. However, in the setting of hypertrophic cardiomyopathy or mitral valve prolapse, vasodilators can increase the severity of MR. To define the precise role of medical therapy, a larger randomized controlled trial is needed to confirm benefit and assess in which subsets of patients medical therapy is most useful. Medical therapy in some patients improves symptoms, lessens MR, and may delay the need for surgical intervention.

Aims Prosthesis–patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) leads to increased mortality. However, its peri-procedural determinants remain unknown. We investigated geometric changes in aortic annulus (AoA) and left ventricular outflow tract (LVOT) during TAVR by three-dimensional transoesophageal echocardiography (3D-TEE) and its association with post-procedural PPM. Methods and results A total of 131 patients with severe aortic stenosis underwent intraprocedural 3D-TEE during balloon-expandable TAVR. The severity of PPM was graded using the indexed effective orifice area calculated by Doppler echocardiography at discharge, with moderate defined as ≥0.65 and ≤0.85 cm2/m2 and severe defined as 86.3% had a sensitivity of 84% and a specificity of 44% for the prevention of severe PPM. Conclusion 3D-TEE can evaluate geometric changes in AoA and LVOT during balloon-expandable TAVR and predicts post-procedural PPM.

A rechargeable battery based on a multivalent Mg/O2 couple is an attractive chemistry due to its high theoretical energy density and potential for low cost. Nevertheless, metal-air batteries based on alkaline earth anodes have received limited attention and generally exhibit modest performance. In addition, many fundamental aspects of this system remain poorly understood, such as the reaction mechanisms associated with discharge and charging. The present study aims to close this knowledge gap and thereby accelerate the development of Mg/O2 batteries by employing first-principles calculations to characterize electrochemical processes on the surfaces of likely discharge products, MgO and MgO2. Thermodynamic limiting potentials for charge and discharge are calculated for several scenarios, including variations in surface stoichiometry and the presence/absence of intermediate species in the reaction pathway. The calculations indicate that pathways involving oxygen intermediates are preferred, as they generally result in higher discharge and lower charging voltages. In agreement with recent experiments, cells that discharge to MgO exhibit low round-trip efficiencies, which are rationalized by the presence of large thermodynamic overvoltages. In contrast, MgO2-based cells are predicted to be much more efficient: superoxide-terminated facets on MgO2 crystallites enable low overvoltages and round-trip efficiencies approaching 90%. These data suggest that the performance of Mg/O2 batteries can be dramatically improved by biasing discharge toward the formation of MgO2 rather than MgO.

Objectives This study of 3-dimensional (3D) transesophageal echocardiography (TEE) aimed to demonstrate features associated with transvalvular aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) and to confirm the fact that a gap between the native aortic annulus and prosthesis is associated with paravalvular AR. Background The mechanism of AR after TAVR, particularly that of transvalvular AR, has not been evaluated adequately. Methods All patients with severe aortic stenosis who underwent TAVR with the Sapien device (Edwards Lifesciences, Irvine, California) had 3D TEE of the pre-procedural native aortic annulus and the post-procedural prosthetic valve. Results In the 201 patients studied, the total AR was mild in 67 patients (33%), moderate in 21 patients (10%), and severe in no patients. There were 20 patients with transvalvular AR and 82 patients with paravalvular AR. Fourteen patients had both transvalvular and paravalvular AR. Patients with transvalvular AR had larger prosthetic expansion (p Conclusions 3D TEE successfully demonstrated the features associated with transvalvular AR, such as large prosthetic expansion, elliptical prosthetic shape, and anti-anatomical position of prosthesis. Additionally, effective area oversizing was associated with paravalvular AR.

This is the second of a series of 4 white papers that represent Expert Consensus Documents developed by the Society of Computed Body Tomography and Magnetic Resonance through its task force on dual-energy computed tomography. This paper, part 2, addresses radiation dose and iodine sensitivity in dual-energy computed tomography.

This is the first of a series of 4 white papers that represent Expert Consensus Documents developed by the Society of Computed Body Tomography and Magnetic Resonance through its task force on dual-energy computed tomography (DECT). This article, part 1, describes the fundamentals of the physical basis for DECT and the technology of DECT and proposes uniform nomenclature to account for differences in proprietary terms among manufacturers.

The development of a practical magnesium-anode battery requires electrolytes that allow for highly efficient magnesium exchange while also being compatible with cathode materials. Here, a one-dimensional continuum-scale model is developed to simulate cyclic plating/stripping voltammetry of a model magnesium-based electrolyte system employing magnesium borohydride/dimethoxyethane [Mg(BH4)2/DME] solutions on a gold substrate. The model is developed from non-electroneutral dilute-solution theory, using Nernst-Planck equations for the mass flux and Poisson's equation for the electrostatic potential. The electrochemical reaction is modeled with multistep Butler-Volmer kinetics, with a modified current/overpotential relationship that separately accounts for the portions of the current responsible for nucleating new deposits and propagating or dissolving existing ones. The diffusivities of the electrolyte species, standard heterogeneous rate constant, charge-transfer coefficient, formal potential, and nucleation overpotential are determined computationally by reproducing experimental voltammograms. The model is computationally inexpensive and therefore allows for broad parametric studies of electrolyte behavior that would otherwise be impractical.

The oxide known as LLZO, with nominal composition Li7La3Zr2O12, is a promising solid electrolyte for Li-based batteries due to its high Li-ion conductivity and chemical stability with respect to lithium. Solid electrolytes may also enable the use of metallic Li anodes by serving as a physical barrier that suppresses dendrite initiation and propagation during cycling. Prior linear elasticity models of the Li electrode/solid electrolyte interface suggest that the stability of this interface is highly dependent on the elastic properties of the solid separator. For example, dendritic suppression is predicted to be enhanced as the electrolyte’s shear modulus increases. In the present study a combination of first-principles calculations, acoustic impulse excitation measurements, and nanoindentation experiments are used to determine the elastic constants and moduli for high-conductivity LLZO compositions based on Al and Ta doping. The calculated and measured isotropic shear moduli are in good agreement and fall ...

Background: In EVEREST II (Endovascular Valve Edge-to-Edge Repair Study), treatment of mitral regurgitation (MR) with a novel percutaneous device showed superior safety compared with surger...

Complication rates remain high after reverse total shoulder arthroplasty (RTSA). Salvage options after implant failure have not been well defined. This study examines the role of reimplantation and revision RTSA after failed RTSA, reporting outcomes and complications of this salvage technique.Sixteen patients underwent component revision and reimplantation after a prior failed RTSA from 2004 to 2011. Indications included baseplate failure (7 patients, 43.8%), instability (6 patients, 37.5%), infection (2 patients, 12.5%), and humeral loosening (1 patient, 6.3%). The average age of the patient during revision surgery was 68.6 years. Outcomes information at follow-up was recorded, including visual analog scale score for pain, subjective shoulder value, American Shoulder and Elbow Surgeons score, and Simple Shoulder Test score, and these were compared with pre-revision values. Repeated surgeries and complications were noted.Average time to follow-up from revision was 58.9 months (minimum, 2 years; range, 24-103 months). The average postoperative visual analog scale score for pain was 1.7/10 (7.5/10 preoperatively; P.0001), and the subjective shoulder value was 62% (17% preoperatively; P.0001). The average postoperative American Shoulder and Elbow Surgeons score was 66.7, and the Simple Shoulder Test score was 52.6. Fourteen patients (88%) noted that they felt "better" postoperatively than before their original RTSA and would go through the procedure again if given the option. Nine patients suffered major complications (56%), and 6 of these ultimately underwent further procedures (38% of cohort).Salvage options after failure of RTSA remain limited. Component revision and reimplantation can effectively relieve pain and improve function compared with baseline values, and patient satisfaction levels are moderately high. However, complication rates and reoperation rates are significant.

Amongst known families of solid electrolytes of potential interest for solid-state batteries, the anti-perovskites (APs) have recently attracted great attention for the high ionic conductivities observed in certain compositions, and, like perovskites, the compositional flexibility provided by the possibility for ion substitution onto multiple lattice sites. [1] For example, variations in the extent of disorder, that are accompanied by changes in the distribution of lithium migration energies.[2] In surveying transport in this family of ion conductors, we observed a trend wherein numerous compositions show upwards curvature on an Arrhenius plot, indicating a non-constant activation energy. This is unusual as most solids exhibiting non-Arrhenius behavior exhibit a negative deviation. The structure origins of such deviations are not well understood. Among the AP-structure SSEs, Li2OHCl and its variants are particularly interesting because of their relatively high conductivities at room temperature. Unlike Li3OCl, where six Li atoms occupy the vertices of the Li6O octahedral, in Li2OHX the vertices are occupied by four lithium atoms with two other sites vacant. H in Li2OHX sits at the oxygen atom in the center of the octahedron. The Li defects and the movement of H around the oxygen atom give rise to a change in the ionic conduction pathway as temperature varies (Figure 1). Figure 1. The ionic conduction pathway of Li and H in Li2OHCl at different temperature Herein, we explain the non-Arrhenius conduction behavior in relation to defect and H movement, and our attempts to understand the structural origin(s) of this behavior through temperature-dependent X-ray and neutron scattering, calorimetry, and other methods. Implications for the design of solid electrolytes for solid state batteries will be discussed. This work was supported as part of the Joint Center for Energy Storage Research, an Energy Innovation Hub funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences. Reference s : [1] Zhao, Y.; Daemen, L. L. Superionic conductivity in Lithium-rich anti-perovskites. J. Am. Chem. Soc. 2012, 134, 15042−15047. [2] Kwangnam Kim and Donald J. Siegel. "Correlating lattice distortions, ion migration barriers, and stability in solid electrolytes." Journal of Materials Chemistry A 7, no. 7 (2019): 3216-3227. Figure 1

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a devastating ongoing global pandemic Its disease severity ranges from asymptomatic, mild to severe disease, which can be complicated by developing hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS) Pulmonary fibrosis is condition that occurs due to scarring of lung tissue Most common cause being idiopathic occurring over a long period of time but it can also occur several days after severe bacterial pneumonias due to activation of fibroblasts Our case shows that Covid-19 infection can acutely cause pulmonary fibrosis CASE PRESENTATION: A 76-year old woman, life time non-smoker, with a history of well controlled intermittent asthma (rescue inhaler only) never hospitalized for any exacerbations She was transferred to our facility due to persistent oxygen requirements after diagnosed with Covid-19 pneumonia She presented to an outside hospital 3 months prior with fever and shortness of breath Her course was complicated with hypoxemia requiring oxygen via non-rebreather mask, bilateral lower extremity deep vein thrombosis requiring apixaban Her oxygen requirement slowly improved to 2 liters via nasal cannula Despite clinically improvement she became oxygen dependent She failed weaning off oxygen multiple times CT of her chest even showed predominant upper lobe scarring She was discharged home with oxygen 5 months after her Covid-19 pneumonia diagnosis DISCUSSION: Pulmonary fibrosis leads to lung scarring Fibrotic tissue is dead tissue, no gas exchange happens and there is a restrictive pattern on Pulmonary function tests (PFTs) There are many different conditions that can lead to pulmonary fibrosis but it is not common to develop post viral infections Classic Covid-19 pneumonia causes diffuse bilateral infiltrates causing severe inflammatory response leading to macrophage activation, cytokine release with activation and proliferation of fibroblasts causing tissue destruction and scarring Except for well controlled intermittent asthma our patient did not have any underlying lung etiologies that could make her oxygen dependent She is a life time non-smoker, no occupational exposure to any chemicals, pollutants, toxic fumes etc , no history of autoimmune diseases or connective tissue diseases, no radiation exposure, no usage of any pulmonary toxic medications like amiodarone, bleomycin Review of old medical records and imaging did not show any evidence of pulmonary fibrosis Unfortunately, there were no post Covid-19 PFTs available for comparison CONCLUSIONS: Covid-19 pneumonia with diffuse bilateral infiltrates can rapidly progress into pulmonary fibrosis due to severe inflammatory response/cytokine storm (post-COVID fibrotic ARDS), which made our patient oxygen dependent with significant reduction in her quality of life Reference #1: Belloli EA, Beckford R, Hadley R, Flaherty KR Idiopathic non-specific interstitial pneumonia Respirology 2016 FEb 21(2): 259-68 Reference #2: Zhu N Zhang D Wang W et al A novel coronavirus from patients with pneumonia in China, 2019 N Engl J Med 2020;382: 727-733 DISCLOSURES: No relevant relationships by Moses Bachan, source=Web Response No relevant relationships by Zinobia Khan, source=Web Response No relevant relationships by swetha Nadella, source=Web Response No relevant relationships by Robert Siegel, source=Web Response No relevant relationships by Vijaya Vudathaneni, source=Web Response

SUMMARY Mechanisms of experience-dependent plasticity have been well characterized in mouse primary visual cortex (V1), including a form of potentiation driven by repeated presentations of a familiar visual sequence (“sequence plasticity”). The prefrontal anterior cingulate cortex (ACC) responds to visual stimuli, yet little is known about if and how visual experience modifies ACC circuits. We find that mouse ACC exhibits sequence plasticity, but in contrast to V1, the plasticity expresses as a change in response timing, rather than a change in response magnitude. Sequence plasticity is absent in ACC, but not V1, in a mouse model of a neurodevelopmental disorder associated with intellectual disability and autism-like features. Our results demonstrate that simple sensory stimuli can be used to reveal how experience functionally (or dysfunctionally) modifies higher-order prefrontal circuits and suggest a divergence in how ACC and V1 encode familiarity., Graphical Abstract, In Brief Sidorov et al. demonstrate that patterned visual input can drive experience-dependent plasticity in the timing of neural responses in mouse anterior cingulate cortex.

Background:Filgotinib (FIL), an oral selective JAK1 inhibitor, has shown efficacy and safety in multiple phase 3 studies in adults with moderately-to-severely active rheumatoid arthritis (RA). We have previously described the molecular response to FIL in large-scale RNA sequencing studies of gene expression in other RA populations1-3and conducted a similar study in methotrexate (MTX)-naïve RA patients (pts) (FINCH3).Objectives:Identify gene transcripts and biological pathways associated with RA and those altered in response to FIL treatment.Methods:MTX-naïve RA pts who were enrolled in FINCH3 (ClinicalTrials.govNCT02886728) received a stable dose of MTX with placebo (PBO+MTX), FIL 200mg alone (FIL 200mg monotherapy), or one of two doses of FIL once daily (QD) together with MTX (FIL 100mg+MTX, FIL 200mg+MTX). Whole blood samples were collected from pts using PAXgene tubes at baseline, week 4, week 12, and week 24. RNA from these samples was extracted and sequenced on the Illumina HiSeq 2500 platform following globin RNA depletion. Correlations between baseline gene expression and disease measurements were performed using Spearman’s rank partial correlation to account for covariates. Differentially expressed genes (DEGs) were identified using voom-limma. Biological pathway analyses were performed on v6.1 of the Molecular Signature Database using single sample gene set enrichment analysis (GSEA) with the focus on immune signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG). A false-discovery rate of 5% was applied for all analyses.Results:Differential gene expression analyses comparing baseline samples with after-treatment samples revealed rapid onset of transcriptional changes in FIL-treated pts, most notably for the two FIL 200mg arms. Fewer DEGs were observed at all timepoints in PBO+MTX treated patients with a peak number at week 24, an observation consistent with the clinical response kinetics of MTX.4Up to 3x as many significant DEGs were observed in the FIL 200mg+MTX arm compared to the FIL 100mg+MTX arm, a finding consistent with the superior clinical efficacy of the FIL 200mg dosage. As with other FIL clinical trial RNA-seq studies and consistent with the selective MoA of FIL, JAK-STAT pathway-induced genes SOCS2 and CISH were significantly downregulated across FIL treatment arms and timepoints, but not for PBO+MTX. RA disease activity-associated genes2-3FAM20A and METTL7B were significantly reduced at all timepoints in FIL-treated pts, but only at week 24 in PBO+MTX pts. While no significant changes in KEGG immune signaling pathways were observed in the PBO+MTX arm, a dose-dependent effect on pathway modulation was observed in the FIL arms, including reductions in JAK-STAT, toll-like receptor, chemokine, and RIG-I like receptor signaling.Conclusion:More rapid and sustained changes of transcriptional activity in the whole blood transcriptional profile of RA pts after FIL treatment were found compared to PBO+MTX. Dose-dependent changes were observed in FIL-treated pts, most notably in the KEGG JAK-STAT signaling pathway. These observations confirm an inhibition of JAK-STAT signaling by FIL and are consistent with the observed clinical efficacy of FIL in these pts.References:[1]Taylor PC, et al. (EULAR 2018).http://dx.doi.org/10.1136/annrheumdis-2018-eular.3759[2]Taylor PC, et al. (ACR 2018).https://doi.org/10.1093/rheumatology/kez105.001[3]Taylor PC, et al. (EULAR 2019).http://dx.doi.org/10.1136/annrheumdis-2019-eular.2509[4]Taylor PC, et al. J Clin Med. 2019;8(4): pii: E515. doi: 10.3390/jcm8040515Acknowledgments:This study was funded by Gilead Sciences, Inc. Editorial support was provided by Fishawack Communications Inc and funded by Gilead Sciences, Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Bryan Downie Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Emon Elboudwarej Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Sam Kim Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Angie Hertz Shareholder of: Gilead Sciences Inc, Employee of: Gilead Sciences Inc, Amer M. Mirza Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Jeffrey Siegel Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Rachael E. Hawtin Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Jinfeng Liu Shareholder of: Gilead Sciences Inc., Roche, Employee of: Gilead Sciences Inc.

Background:Filgotinib (FIL), an oral selective JAK1 inhibitor, has shown efficacy and safety in multiple phase 3 studies in adults with moderately-to-severely active rheumatoid arthritis (RA). We have previously described the molecular response to FIL in large-scale RNA sequencing studies of gene expression in other RA populations1-3and herein conducted a similar study in RA patients (pts) with prior inadequate response to methotrexate (MTX; FINCH1).Objectives:Identify RA-associated gene transcripts and biological pathways that are altered in response to FIL treatment.Methods:RA pts who had an inadequate response to MTX were enrolled in FINCH1 (ClinicalTrials.govNCT02889796) and randomized to receive either a stable dose of MTX with placebo (PBO+MTX), adalimumab (ADA+MTX), or one of two doses of FIL (FIL 100mg+MTX, FIL 200mg+MTX) once daily (QD). Whole blood samples were collected from pts using PAXgene tubes at baseline, week 4, and week 12. RNA from these samples was extracted and sequenced on the Illumina HiSeq 2500 platform following globin RNA depletion. Correlations between baseline gene expression and disease measurements were performed using Spearman’s rank partial correlation with covariates. Differentially expressed genes (DEGs) were identified using voom-limma. Pathway analysis was performed on v6.1 of the Molecular Signature Database using single sample gene set enrichment analysis (GSEA) with the focus on immune signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG). A false-discovery rate of 5% was applied for all analyses.Results:Differential gene expression analyses comparing baseline samples with after-treatment samples revealed more rapid transcriptional kinetics for FIL-treated pts compared to ADA+MTX-treated pts. No significant DEGs were observed in PBO-treated pts. More significant DEGs were observed in the FIL 200mg+MTX arm compared to the FIL 100mg+MTX arm, consistent with the superior clinical efficacy of the FIL 200mg dosage. As with other FIL clinical trial RNA-seq studies and consistent with the selective MoA of FIL, JAK-STAT pathway-induced genes SOCS2 and CISH were significantly downregulated across both FIL treatment arms and timepoints, but not in the ADA+MTX arm. RA disease activity associated genes2-3FAM20A and METTL7B were significantly reduced at both 4 and 12 weeks only in the FIL 200mg+MTX arm. While no significant changes in KEGG immune signaling pathways were observed in the PBO+MTX arm, a dose-dependent effect on pathway modulation was observed in the FIL arms. The most prominently down-regulated KEGG pathways included JAK-STAT signaling and leukocyte transendothelial migration.Conclusion:More rapid and sustained changes of transcriptional activity were observed in the whole blood transcriptional profile of RA pts following FIL 200mg+MTX compared to ADA+MTX treatment. Dose-dependent changes were observed in FIL-treated pts, most notably in the KEGG JAK-STAT signaling pathway. These observations confirm an inhibition of JAK-STAT signaling by FIL and are consistent with the observed clinical efficacy of FIL in these pts.References:[1]Taylor PC, et al. (EULAR 2018).http://dx.doi.org/10.1136/annrheumdis-2018-eular.3759[2]Taylor PC, et al. (ACR 2018).https://doi.org/10.1093/rheumatology/kez105.001[3]Taylor PC, et al. (EULAR 2019).http://dx.doi.org/10.1136/annrheumdis-2019-eular.2509Acknowledgments :This study was funded by Gilead Sciences, Inc. Editorial support was provided by Fishawack Communications Inc and funded by Gilead Sciences, Inc.Disclosure of Interests: :Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Bryan Downie Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Emon Elboudwarej Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Sam Kim Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Angie Hertz Shareholder of: Gilead Sciences Inc, Employee of: Gilead Sciences Inc, Amer M. Mirza Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Jeffrey Siegel Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Rachael E. Hawtin Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Jinfeng Liu Shareholder of: Gilead Sciences Inc., Roche, Employee of: Gilead Sciences Inc.

Li-ion batteries (LIBs) are the most widely used energy storage devices. Beyond Li, Na and K ion systems are being explored for grid energy storage. Additionally, multivalent (MV) ions like Mg, Ca, and Al have the potential to increase the volumetric capacity of batteries. Currently, additional improvements in battery technologies are being driven by demands for longer-lasting batteries and safety concerns. Safety hazards in LIBs originate from the use of liquid electrolytes, which are volatile and flammable. In principle, these safety problems can be circumvented by the use of a solid electrolyte (SE). Furthermore, SEs may enable the use of metallic anodes which significantly increase the energy density. Recently, Li and Na anti-perovskites (AP) have been suggested as SEs. APs adopt the formula X3AB, where X is a monovalent cation and A and B are anions with respective charges of -2 and -1. Using a series of model APs with X = Li, Na, or K, A = O, S, or Se, and B = F, Cl, Br, or I, our previous study revealed that ‘lattice distortion’ can enhance ion mobility. We found that symmetry-lowering lattice distortions correlate with lower percolating migration barriers and reduced thermodynamic stability. Therefore, ‘distortion tuning’ can result in SE materials by balancing a mobility/stability tradeoff. Thus far, few MV SEs have been reported, and the discovery of MV SEs remains an important pursuit to advance the prospects for MV solid-state batteries. Previous literature showed that most alkaline earth metals, 3d transition metals, and lanthanides can reside in the X site of the AP system. These materials exhibit a wide range of electronic, magnetic, and thermal properties, and have been exploited in applications ranging from thermoelectrics, memory devices, sensors, and optical devices. Among the many possible MV APs, here we focus on ten non-metallic Mg and Ca APs for MV SEs, i.e., Mg3NB, Ca3NB, Ca3PSb, and Ca3AsSb (where B = P, As, Sb, or Bi). First-principles calculations were used to evaluate suitability for SE applications by predicting equilibrium structures, band gaps, elastic moduli, percolating migration barriers, defect formation energies, and thermodynamic (electro)chemical stability. All compounds are predicted to be thermodynamically stable. Ca and Mg APs follow a similar trend to that observed in monovalent APs, where lattice distortions decrease the barriers for percolating ion migration. These MV APs are also predicted to have high defect formation energies, implying that defect concentrations need to be frozen in during synthesis at high temperatures. We found that Mg3NAs, Ca3NAs, and Ca3PSb have relatively low percolating barriers of less than 500 meV for vacancy migration and less than 200 meV for dumbbell migration. Band gaps are predicted to be larger than 2 eV. Also, these systems are stable against the respective metal anode and expected to have moderate oxidative stability up to 1.2, 1.7, and 1.4 V, respectively, implying that coating materials may be needed to prevent oxidation by the cathode and increase the operating voltage.

Models based on linear elasticity suggest that a solid electrolyte with a high shear modulus will suppress "dendrite" formation in batteries that use metallic lithium as the negative electrode. Nevertheless, recent experiments find that lithium can penetrate stiff solid electrolytes through microstructural features, such as grain boundaries. This failure mode emerges even in cases where the electrolyte has an average shear modulus that is an order of magnitude larger than that of Li. Adopting the solid-electrolyte Li