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Much evidence suggests that hypofunction of the N-methyl- d -aspartate glutamate receptor (NMDAR) may contribute broadly towards a subset of molecular, cognitive and behavioral abnormalities common among psychiatric and developmental diseases. However, little is known about the specific molecular changes that lead to NMDAR dysfunction. As such, personalized approaches to remediating NMDAR dysfunction based on a specific etiology remains a challenge. Sarcoma tyrosine kinase (Src) serves as a hub for multiple signaling mechanisms affecting GluN2 phosphorylation and can be disrupted by convergent alterations of various signaling pathways. We recently showed reduced Src signaling in post mortem tissue from schizophrenia patients, despite increased MK-801 binding and NMDA receptor complex expression in the postsynaptic density (PSD). These data suggest that Src dysregulation may be an important underlying mechanism responsible for reduced glutamate signaling. Despite this evidence for a central role of Src in NMDAR signaling, little is known about how reductions in Src activity might regulate phenotypic changes in cognition and behavior. As such, the current study sought to characterize behavioral and electrophysiological phenotypes in mice heterozygous for the Src Acl gene (Src+/− mice). Src+/− mice demonstrated decreased sociability and working memory relative to Src+/+ (WT) mice while no significant differences were seen on locomotive activity and anxiety-related behavior. In relation to WT mice, Src+/− mice showed decreased mid-latency P20 auditory event related potential (aERP) amplitudes, decreased mismatch negativity (MMN) and decreased evoked gamma power, which was only present in males. These data indicate that Src+/− mice are a promising new model to help understand the pathophysiology of these electrophysiological, behavioral and cognitive changes. As such, we propose that Src+/− mice can be used in the future to evaluate potential therapeutic approaches by targeting increased Src activity as a common final pathway for multiple etiologies of SCZ and other diseases characterized by reduced glutamate function.

Fragile X Syndrome is a neurodevelopmental disorder which affects intellectual, social and physical development due to mutation of the Fragile X mental retardation 1 (FMR1) gene. The resultant loss of Fragile X mental retardation protein can be modelled by Fmr1 gene knockout (KO) in mice. The current study investigated the behavioural effects of cannabidiol (CBD; a non-psychoactive phytocannabinoid) in male Fmr1 KO mice as a preclinical model for therapeutic discovery. Vehicle or CBD (5 or 20 mg/kg body weight) was administered to adult Fmr1 KO and wild type-like (WT) mice before they were tested in behavioural tasks including: open field (OF), elevated plus maze (EPM), spontaneous alternation, social preference, and passive avoidance tasks. Fmr1 KO mice were hyperlocomotive and hyperexplorative and habituated more slowly to a novel environment compared to control animals. Furthermore, Fmr1 KO mice showed fewer anxiety-related behaviours across tests. Effects of CBD were subtle and limited to the EPM, where CBD decreased the anxiety response of all mice tested. Acute CBD had no impact on locomotion or anxiety-related parameters in the OF. Cognitive performance of Fmr1 KO mice was equivalent to controls and not affected by CBD treatment. Brain concentrations of CBD were equivalent between genotypes, but in animals sacrificed 90 min post-administration, decreased plasma CBD in Fmr1 KO mice compared to WT suggested more rapid clearance of CBD by transgenic animals. Overall, acute CBD at the doses chosen did not selectively normalize behavioural abnormalities in Fmr1 KO mice, but reduced anxiety-like behaviour in both Fmr1 KO and WT mice.

Metal organic framework (MOF) materials have emerged as the adsorbent materials with the highest H2 storage densities on both a volumetric and gravimetric basis. While measurements of hydrogen storage at the material level (primarily at 77 K) have been published for hundreds of MOFs, estimates of the system-level hydrogen storage capacity are not readily available. In this study, hydrogen storage capacities are estimated at the system-level for MOFs with the highest demonstrated volumetric and gravimetric H2 storage densities. System estimates are based on a single tank cryo-adsorbent system that utilizes a type-1 tank, multi-layer vacuum insulation, liquid N2 cooling channels, in-tank heat exchanger, and a packed MOF powder inside the tank. It is found that with this powder-based system configuration, MOFs with ultra-high gravimetric surface areas and hydrogen adsorption amounts do not necessarily provide correspondingly high volumetric or gravimetric storage capacities at the system-level. Meanwhile, attributes such as powder packing efficiency and system cool-down temperature are shown to have a large impact on the system capacity. These results should shed light on the material properties that must to be optimized, as well as highlight the important design challenges for cryo-adsorbent hydrogen storage systems.

Numerous mental health disorders are characterized by cognitive impairments that result in poor vocational and social outcomes. Among the cognitive domains commonly affected, working memory deficits have been noted in patients with attention-deficit/hyperactivity disorder (Martinussen et al. in J Am Acad Child Adolesc Psychiatry 44:377–384, 2005), post-traumatic stress disorder (Honzel et al. in Cogn Affect Behav Neurosci 14:792–804, 2014), and consistently with schizophrenia patients (Callicott et al. in Cereb Cortex 10:1078–1092, 2000; Lewis et al. in Front Hum Neurosci 10:85, 2005; Amann et al. in Brain Res Bull 83:147–161, 2010; Limongi et al. in Schizophr Res 197:386–391, 2018). Oscillations in neural activity from electroencephalogram (EEG) recordings are decomposed by frequency, and band-specific decreases in gamma power (> 30 Hz) have been correlated with working memory ability. This study examined within-subject changes in power of frequency-specific bands during sample versus choice trials during a spatial working memory paradigm (T-maze). EEG was recorded using a relatively novel wireless EEG telemetry system fully implanted within the mouse, enabling uninhibited movement during behavioral tasks. No significant differences were found between sample and correct choice phases in the alpha, theta or gamma frequency ranges. Evoked power was significantly higher during the choice phase than the sample phase in the high-beta/low-gamma frequency range. This frequency range has been implicated in the propagation of cortical predictions to lower levels of stimuli encoding in a top-down hierarchical manner. Results suggest there is an increase in brain activity during correct trials when the mouse enters the opposite arm during the choice phase compared to the sample phase, likely due to prediction error resulting from a discrepancy between present and prior experience. Future studies should identify specific cortical networks involved and investigate neural activity at the neuronal level.

Dual-energy CT enables the simultaneous acquisition of CT images at two different x-ray energy spectra. By acquiring high- and low-energy spectral data, dual-energy CT can provide unique qualitative and quantitative information about tissue composition, allowing differentiation of multiple materials including iodinated contrast agents. The two dual-energy CT postprocessing techniques that best exploit the advantages of dual-energy CT in children are the material-decomposition images (which include virtual nonenhanced, iodine, perfused lung blood volume, lung vessel, automated bone removal, and renal stone characterization images) and virtual monoenergetic images. Clinical applications include assessment of the arterial system, lung perfusion, neoplasm, bowel diseases, renal calculi, tumor response to treatment, and metal implants. Of importance, the radiation exposure level of dual-energy CT is equivalent to or less than that of conventional single-energy CT. In this review, the authors discuss the basic principles of the dual-energy CT technologies and postprocessing techniques and review current clinical applications in the pediatric chest and abdomen.

In this brief overview, I offer a conceptual approach to the mind that can support whatever clinical, research, public policy, or other approach you may be involved with. It seeks to help both the understanding and cultivating of mental health and well-being in our world, and may be especially important in encouraging future psychotherapists to be systems-oriented and multidisciplinary in their work. As the ideas of this framework have been published in a number of texts, I will simply have a brief listing of those and other selected publications at the end of this article and outline the main ideas and factual points as we move along. PRACTITIONER POINTS: Consilience across wide range of disciplines leads to an integrated framework defining the mind, mental health, and the strategies of intervention to cultivate well-being.

Altered gamma-band electrophysiological activity in individuals with autism spectrum disorder (ASD) is well documented, and analogous gamma-band alterations are recapitulated in several preclinical murine models relevant to ASD. Such gamma-band activity is hypothesized to underlie local circuit processes. Gamma-band cross-frequency coupling (CFC), a related though distinct metric, interrogates local neural circuit signal integration. Several recent studies have observed perturbed gamma-band CFC in individuals with ASD, although the direction of change remains unresolved. It also remains unclear whether murine models relevant to ASD recapitulate this altered gamma-band CFC. As such, this study examined whether mice with parvalbumin (PV) cell-specific ablation of NMDA-R1 (PV(cre)/NR1(fl/fl)) demonstrated altered gamma-band CFC as compared with their control littermates (PV(cre)/NR1(+/+)—mice that do not have the PV cell-specific ablation of NMDA-R1). Ten mice of each genotype had 4 min of “resting” electroencephalography recorded and analyzed. First, resting electrophysiological power was parsed into the canonical frequency bands and genotype-related differences were subsequently explored so as to provide context for the subsequent CFC analyses. PV(cre)/NR1(fl/fl) mice exhibited an increase in resting power specific to the high gamma-band, but not other frequency bands, as compared with PV(cre)/NR1(+/+). CFC analyses then examined both the standard magnitude (strength) of CFC and the novel metric Phase(Max)—which denotes the phase of the lower frequency signal at which the peak higher frequency signal power occurred. PV(cre)/NR1(fl/fl) mice exhibited altered Phase(Max), but not strength, of gamma-band CFC as compared with PV(cre)/NR1(+/+) mice. As such, this study suggests a potential novel metric to explore when studying neuropsychiatric disorders.

Few hydrogen adsorbents balance high usable volumetric and gravimetric capacities. Although metal-organic frameworks (MOFs) have recently demonstrated progress in closing this gap, the large number of MOFs has hindered the identification of optimal materials. Here, a systematic assessment of published databases of real and hypothetical MOFs is presented. Nearly 500,000 compounds were screened computationally, and the most promising were assessed experimentally. Three MOFs with capacities surpassing that of IRMOF-20, the record-holder for balanced hydrogen capacity, are demonstrated: SNU-70, UMCM-9, and PCN-610/NU-100. Analysis of trends reveals the existence of a volumetric ceiling at ∼40 g H2 L−1. Surpassing this ceiling is proposed as a new capacity target for hydrogen adsorbents. Counter to earlier studies of total hydrogen uptake in MOFs, usable capacities in the highest-capacity materials are negatively correlated with density and volumetric surface area. Instead, capacity is maximized by increasing gravimetric surface area and porosity. This suggests that property/performance trends for total capacities may not translate to usable capacities., Considering the large number of existing synthesised and hypothesised metal-organic frameworks, determining which materials perform best for given applications remains a challenge. Here, the authors screen the usable hydrogen uptake capacities of nearly 500,000 MOFs, and find that three frameworks outperform the current record-holder.

Atrial fibrillation is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), occurring in approximately 25% of patients, which is four to six times more common than in similarly aged patients of the general population. Atrial fibrillation is poorly tolerated by HCM patients, largely due to their dependence on atrial systole for left ventricular filling. HCM patients who develop atrial fibrillation have an increased rate of heart failure related mortality and disabling or fatal thromboembolic events, as well as functional deterioration due to progressive heart failure when left untreated. Atrial fibrillation is both common in HCM and may lead to significant morbidity and mortality. Accurate risk stratification for atrial fibrillation in this population is crucial as contemporary treatments are highly successful. In this paper, we review the current understanding of known risk factors for atrial fibrillation, including different imaging-based parameters that assess left atrial structural and functional remodeling, electrocardiographic changes that reflect left atrial electrical remodeling, and a focus on comorbid obstructive sleep apnea, and in addition we review variables that have been reported to be predictive of atrial fibrillation. Last, we summarize the accumulating evidence for HCM patients having an intrinsic atrial myopathy.

While proficient cardiac resuscitation has improved survival following cardiac arrest during road races in Japan, this accomplishment does not address coronary artery disease as the underlying cause of an increasing frequency of cardiac arrest in middle-aged men during marathons and ironman triathlons in the United States since the year 2000. Based on the high prevalence of subclinical coronary artery disease by cardiac computed tomography in endurance athletes with low conventional cardiac risk-factor profiles, we recommend coronary artery calcium scores as a more reliable and independent predictor of incident cardiac events, including death, as validated among adults aged 30-46 years. Scores of over 100 Agatston units indicate a 10-year cardiac risk of 7.5%, at which additional measures for primary prevention are recommended, including aspirin, as shown conclusively to reduce first myocardial infarctions in same-aged men in a prospective double-blind controlled trial. Targeted screening for subclinical coronary atherosclerosis with coronary artery calcium scores is prudent to guide appropriately dosed aspirin use to mitigate the increasing frequency of sports-related sudden cardiac death due to plaque rupture.

Rechargeable batteries employing metal negative electrodes (i.e., anodes) are attractive next-generation energy storage devices because of their greater theoretical energy densities compared to intercalation-based anodes. An important consideration for a metal's viability as an anode is the efficiency with which it undergoes electrodeposition and electrodissolution. The present study assesses thermodynamic deposition/dissolution efficiencies and associated nucleation rates for seven metals (Li, Na, K, Mg, Ca, Al, and Zn) of relevance for battery applications. First-principles calculations were used to evaluate thermodynamic overpotentials at terraces and steps on several low-energy surfaces of these metals. In general, overpotentials are observed to be the smallest for plating/stripping at steps and largest at terrace sites. The difference in the coordination number for a surface atom from that in the bulk was found to correlate with the overpotential magnitude. Consequently, because of their low bulk coordination, the body-centered alkali metals (Li, Na, and K) are predicted to be among the most thermodynamically efficient for plating/stripping. In contrast, metals with larger bulk coordination such as Al, Zn, and the alkaline earths (Ca and Mg) generally exhibit higher thermodynamic overpotentials. The rate of steady-state nucleation during electrodeposition was estimated using a classical nucleation model informed by the present first-principles calculations. Nucleation rates are predicted to be several orders of magnitude larger on alkali metal surfaces than on the other metals. This multiscale model highlights the sensitivity of the nucleation behavior on the structure and composition of the electrode surface.

Left atrial appendage (LAA) thrombus in nonvalvular atrial fibrillation or flutter (AF) is a major cause of stroke and presents a therapeutic dilemma in a rhythm-control strategy. The prevalence and resolution of LAA thrombus has not been studied well in the era of non-vitamin K antagonist oral anticoagulant use. This study sought to establish (1) the prevalence of LAA thrombus (2) the prevalence of LAA thrombus despite antithrombotic therapy, (3) the rate of persistence of LAA thrombus despite appropriate anticoagulant prescriptions, and (4) determinants of LAA thrombus persistence. Consecutive transesophageal echocardiograms (TEE) performed in patients with AF were reviewed to estimate the overall prevalence of LAA thrombus and the resolution rate in those with repeat studies. Multivariable logistic regression was used to identify clinical and echocardiographic predictors of thrombus resolution. Of 1,485 patients with AF, 117 (8%) had LAA thrombus. Of those, 62 had repeat TEE within 1 year and 58 (94%) were prescribed adequate anticoagulation in TEE studies (mean interval 96 ± 72 days). Thirty-seven patients (60%) had LAA thrombus resolution. Thrombus resolution rate was only 79% in patients considered on appropriate anticoagulation. Patients with persistent LAA thrombus were more likely to have diabetes; no other clinical or echocardiographic variable was independently associated with thrombus resolution. There was no significant difference in LAA thrombus resolution between non-vitamin K antagonist oral anticoagulants and warfarin. LAA thrombus persistence despite adequate anticoagulation is relatively common and difficult to predict clinically; TEE before electrical cardioversion should be considered regardless of anticoagulation status.

The emergence of solid electrolytes with ionic conductivities comparable to that of liquids has improved the prospects for realizing solid-state batteries. Although a small number of ionically-conducting solids are now known, most exhibit shortcomings such as limited interfacial stability and susceptibility to dendrite penetration. Consequently, the discovery of alternative solid electrolytes remains an important goal. This search has been slowed, however, by incomplete understanding of the elementary chemical and structural features that give rise to high ionic mobility. Here we characterize the atomic-scale connections between mobility, thermodynamic stability, and lattice distortions. The degree of lattice distortion, described by the tolerance factor, t, was systematically varied via isovalent composition variation across a series of model anti-perovskite ion conductors. Larger distortions are observed to correlate strongly with lower energy barriers for percolating ion migration: distortions suppress corrugations of the potential energy surface by widening a subset of migration channels and by destabilizing equilibrium configurations. As larger distortions also correlate with reduced stability, realizing high ionic mobility in this class of conductors requires balancing a mobility/stability tradeoff. Na3SI is identified as one such balanced material.

A major challenge toward realizing high-performance aqueous lithium batteries (ALBs) is the utilization of a metallic lithium anode. However, an ideal solid electrolyte that can protect metallic lithium from reacting with aqueous solutions while still maintaining a high lithium ion conduction is not currently available. One obstacle is the lack of a reliable experimental tool to differentiate the conduction behaviour of H+ and Li+ ions in a solid electrolyte. Here, by correlating neutron and electron spectroscopy, we quantitatively reveal the mobility and lattice occupancy of the two ions individually in protonated cubic Li6.25Al0.25La3Zr2O12 (LLZO). Our results not only highlight LLZO as a potential effective separation layer for ALBs but also present a robust method to quantify the mobility of individual mobile ions in solid-state ion conductors.

Few treatments exist for the cognitive symptoms of schizophrenia. Pharmacological agents resulting in glutamate N-methyl-d-aspartate (NMDA) receptor hypofunction, such as MK-801, mimic many of these symptoms and disrupt neural activity. Recent evidence suggests that deep brain stimulation (DBS) of the medial septal nucleus (MSN) can modulate medial prefrontal cortex (mPFC) and hippocampal activity and improve spatial memory.Here, we examine the effects of acute MK-801 administration on oscillatory activity within the septohippocampal circuit and behavior. We also evaluate the potential for MSN stimulation to improve cognitive behavioral measures following MK-801 administration.59 Sprague Dawley male rats received either acute intraperitoneal (IP) saline vehicle injections or MK-801 (0.1 mg/kg). Theta (5-12 Hz), low gamma (30-50 Hz) and high frequency oscillatory (HFO) power were analyzed in the mPFC, MSN, thalamus and hippocampus. Rats underwent MSN theta (7.7 Hz), gamma (100 Hz) or no stimulation during behavioral tasks (Novel object recognition (NOR), elevated plus maze, Barnes maze (BM)).Injection of MK-801 resulted in frequency-specific changes in oscillatory activity, decreasing theta while increasing HFO power. Theta, but not gamma, stimulation enhanced the anxiolytic effects of MK-801 on the elevated plus maze. While MK-801 treated rats exhibited spatial memory deficits on the Barnes maze, those that also received MSN theta, but not gamma, stimulation found the escape hole sooner.These findings demonstrate that acute MK-801 administration leads to altered neural activity in the septohippocampal circuit and impaired spatial memory. Further, these findings suggest that MSN theta-frequency stimulation improves specific spatial memory deficits and may be a possible treatment for cognitive impairments caused by NMDA hypofunction.

Early life stress may have profound effects on brain health, yielding both short- and long-term cognitive or psychiatric impairment. Early life Social Instability Stress (SIS) in rodents has been used to model the effects of early chronic human stress. While many studies have assessed acute and short-term responses to this stressor, less attention has been paid to the lasting effects of early life stress in rodents.The current study utilized SIS in young mice to assess the impact of early life adversity over the lifespan. Mice were assessed in adulthood between the ages of 18 to 66 weeks for changes in behaviors associated with anxiety, affect, sociability, aggression, motivation, and recognition memory. Additionally, mice were assessed for changes in glucocorticoid level and hippocampal mRNA expression in a subset of genes that display alterations in humans following exposure to stress (CRHR1, CRHR2, FKBP5, SLC6A4).Mice exposed to early SIS showed disrupted memory and increased hippocampal expression of FKBP5, CRHR2 and SLC6A4 mRNA compared to non-stressed mice. Importantly, there was a significant association between increased FKBP5 and CRHR2 with reduced recognition memory. Additionally, mice exposed to SIS showed increased responding on a progressive ratio schedule of reinforcement, indicating that reduction in memory performance was not mediated by decreased effort.Ecologically-relevant social stress in mice causes long-term decrements in recognition memory, possibly mediated by persistent changes in moderators of the stress cascade. Additionally, animals exposed to early life stress showed increased motivation for reward, which may contribute to a host of hedonic seeking behaviors throughout life. These data suggest that SIS can be used to evaluate therapeutic interventions to attenuate or reverse lasting effects of early life adversity.

The past decade has been a revolution in the use of percutaneous procedures for mitral valve (MV) therapy, and currently there are several devices in different stages of development. The enhanced imaging with 3D transoesophageal echocardiography (TEE), as well as computed tomography (CT) and fusion imaging, has led to better understanding of MV anatomy, which in turn helped promote the development of new devices, as well as being crucial for procedural guidance and effective valve repair or replacement. In addition to the new devices, fusion imaging promises to result in even better outcomes in the future by enhancing device deployment. While initially device development for the MV focused on degenerative mitral regurgitation (MR), more recent studies have demonstrated that reducing the severity of secondary MR with transcatheter techniques may provide symptomatic benefit with regards to cardiac heart failure and improved survival. Percutaneous therapies for the MV, as they are less invasive, have many advantages that may supplant surgical techniques, provided that they reduce morbidity and mortality and have comparable efficacy. In this chapter we review transcatheter MV interventions for mitral stenosis (MS) and MR.

In patients with moderate aortic stenosis (AS), heart failure (HF) symptoms are often unrelated to the AS severity, and the causes of HF symptoms are often unclear. Hypertension is known as one of the most common comorbidities in degenerative AS. Therefore, we assessed the impact of systolic blood pressure (BP) on HF symptoms in patients with moderate AS. We retrospectively analyzed 317 patients with moderate AS (mean transaortic pressure gradient 20 to 39 mm Hg) and preserved left ventricular ejection fraction (left ventricular ejection fraction ≥50%). We classified patients according to the presence or absence of HF symptoms. One hundred patients (32%) had HF symptoms. Symptomatic patients had higher systolic BP (141±21 versus 129±21 mm Hg; p

BACKGROUND Left ventricular (LV) outflow tract (LVOT) obstruction increases mortality in patients undergoing transcatheter mitral valve implantation (TMVI) in degenerated bioprostheses, annuloplasty rings, and native mitral valves. We aimed to evaluate the LVOT area after TMVI using 3-dimensional (3D) transesophageal echocardiography (TEE) and to investigate the preprocedural cardiac geometry that affects the LVOT area after TMVI. METHODS We retrospectively reviewed echocardiography data in 43 patients who had TMVI. A change in pressure gradient across LVOT from before to after TMVI (∆PG) and postprocedure 3D LVOT cross-sectional area at the level of the most distal portion of the mitral valve stent that was closest to the LV apex were assessed as evidence of LVOT narrowing. RESULTS Transcatheter mitral valve implantation with the use of balloon-expandable valve system was performed for 24 bioprostheses, 7 annuloplasty rings, and 12 native valves. Compared to patients without increase in LVOT gradient (∆PG

To evaluate candidacy for surgical mitral valve (MV) repair of recurrent mitral regurgitation (MR) after failed MitraClip.Percutaneous mitral repair with MitraClip is safe and effective in patients with degenerative and functional MR with high surgical risk. However, some patients require subsequent mitral surgery for recurrence of significant MR.This single-center, observational study includes consecutive patients who underwent mitral surgery after failed MitraClip.Twenty-five patients (age, 69 ± 15 years; 52% women) with severe symptomatic MR after failed MitraClip implantation underwent mitral surgery after a median interval of 5.1 months (interquartile range, 2.5-14 months). Ten patients underwent MV repair (8 with robotic minithoracotomy) and 15 underwent MV replacement (most with sternotomy). Two patients in whom MV repair was intended underwent MV replacement because MitraClip-related leaflet damage prohibited repair. Examples of relative contraindication for MV repair that led to pursuing MV replacement were advanced patient age in 4 patients (mean age, 85 ± 7.6 years), endocarditis in 1 patient, and severely calcified or rheumatic leaflets in 5 patients. Perioperative complications were rare and intermediate-term mortality was similar between groups (3 patients in the MV repair group [30%] vs 4 patients in the MV replacement group [27%]; P=.90).When performed by an experienced mitral surgeon and within 1 year of failed MitraClip implantation, surgical MV repair is feasible in most patients who were surgical repair candidates before the clip. Having the option for surgical MV repair after failed MitraClip is important to preserve optimal long-term outcomes for patients who undergo transcatheter mitral repair with MitraClip, especially as ongoing trials are shifting to study lower-risk patients who are also candidates for surgical repair.

BACKGROUND: Patients hospitalized with coronavirus disease 2019 (COVID-19) often have abnormal findings on transthoracic echocardiography (TTE). However, although not all abnormalities on TTE result in changes in clinical management, performing TTE in recently infected patients increases disease transmission risks. It remains unknown whether common biomarker tests, such as troponin and B-type natriuretic peptide (BNP), can help distinguish in which patients with COVID-19 TTE may be safely delayed until infection risks subside. METHODS: Using electronic health records data and chart review, the authors retrospectively studied all patients hospitalized with COVID-19 in a multisite health care system from March 1, 2020, to January 15, 2021, who underwent TTE within 14 days of their first positive COVID-19 result and had BNP and troponin measured before or within 7 days of TTE. The primary outcome was the presence of one or more urgent echocardiographic findings, defined as left ventricular ejection fraction ≤ 35%, wall motion score index ≥ 1.5, moderate or greater right ventricular dysfunction, moderate or greater pericardial effusion, intracardiac thrombus, pulmonary artery systolic pressure > 50 mm Hg, or at least moderate to severe valvular disease. Stepwise logistic regression was conducted to determine biomarkers and comorbidities associated with the outcome. The performance of a rule for classifying TTE using troponin and BNP was evaluated. RESULTS: Four hundred thirty-four hospitalized and 151 intensive care unit patients with COVID-19 were included. Urgent findings on TTE were present in 105 patients (24.2%). Troponin and BNP were abnormal in 311 (71.7%). Heart failure (odds ratio, 5.41; 95% CI, 2.61-11.68), troponin > 0.04 ng/mL (odds ratio, 4.40; 95% CI, 2.05-10.05), and BNP > 100 pg/mL (odds ratio, 5.85; 95% CI, 2.35-16.09) remained significant predictors of urgent findings on TTE after stepwise selection. No urgent findings on TTE were seen in 95.1% of all patients and in 91.3% of intensive care unit patients with normal troponin and BNP. CONCLUSIONS: Troponin and BNP were highly associated with urgent echocardiographic findings and may be used in triaging algorithms for determining in which patients TTE can be safely delayed until after their peak infectious window has passed.

Background: A new grading of tricuspid regurgitation (TR) beyond severe has been proposed. However, few studies assessing the validity of such a new grading scheme of TR have been conducted. Therefore, we evaluated associations of TR grades beyond severe with patient outcome and hemodynamics. Methods: We retrospectively studied patients who underwent 2-dimensional echocardiography and were diagnosed with severe TR between January 2014 and December 2015. According to the vena contracta width of TR (VC), the patients were classified into 2 groups: VC under 14 mm (VC Results: A total of 679 patients (mean 72±17 years, 56% women) were included. During follow-up (median, 158 days; range, 29–891), 210 patients experienced cardiovascular events. By multivariate analysis, VC≥14 mm and left ventricular ejection fraction were independent predictors of cardiovascular events (hazard ratio, 1.57 [1.06–2.33]; hazard ratio, 0.99 [0.98–0.99], respectively). Patients with VC≥14 mm had significantly lower cardiac index (median, 1.8 versus 2.1 L/min per m 2 , P =0.001) and a higher prevalence of right atrial pressure 15 mm Hg (74% versus 60%, P P =0.004). The new subset classification developed by cardiac index and right atrial pressure both on echocardiography predicted cardiovascular events (Log-rank P Conclusions: The relationship of VC≥14 mm to adverse outcome and poor hemodynamics showed the clinical relevance and need of a new grading system beyond severe. The new hemodynamic subset classification provides additional prognostic value for cardiovascular events in patients with severe TR.

Background: Left ventricular (LV) outflow tract (LVOT) obstruction increases mortality in patients undergoing transcatheter mitral valve implantation (TMVI) in degenerated bioprostheses, annuloplasty rings, and native mitral valves. We aimed to evaluate the left ventricular outflow tract area after TMVI using 3-diensional (3D) transesophageal echocardiography (TEE) and to investigate the pre-procedural cardiac geometry affects the LVOT area after TMVI. Methods: We retrospectively reviewed echocardiography data in 43 patients who had TMVI. A change in pressure gradient across LVOT from before to after TMVI (∆PG) and post-procedure 3D cross sectional area (CSA) at the level of the most distal portion of the mitral valve stent that was closest to the LV apex were assessed as evidence of LVOT narrowing. Results: TMVI with the use of balloon-expandable valve system was performed for 24 bioprostheses, 7 annuloplasty rings, and 12 native valves. Compared to patients without increase in LVOT gradient (∆PG

Aims: The DYNAMIC trial assessed the safety and explored the efficacy of multivessel intracoronary infusion of allogeneic cardiosphere-derived cells (CDCs) in patients with heart failure and reduced ejection fraction (HFrEF). Here we report the results of the DYNAMIC trial. Methods and results: We enrolled 14 patients with EF ≤35% and NYHA Class III-IV despite maximal medical and device-based therapy in this single-centre, open-label trial. Intracoronary catheterisation delivered four escalating doses (totalling 37.5-75 million cells) by sequential non-occlusive technique to all three major coronary arteries. The primary safety endpoint was a composite of post-infusion TIMI flow, ventricular tachycardia/fibrillation, sudden death, major adverse cardiac events or acute myocarditis within 72 hours. Twelve patients were male and EF averaged 23.0% (±4.5%). No primary safety endpoints were observed. Two patients died of HFrEF progression nine and 12 months following infusion. Compared to baseline, there was an improvement in EF (26.8% vs 22.9%, p=0.023) and left ventricular end-systolic volume (139.5 vs 177.8 cm3, p=0.03) at six months. Quality of life (QoL) scores and NYHA class (p=0.006) improved at six months. At 12 months, the improvement in EF and QoL remained significant. Conclusions: Global intracoronary infusion of allogeneic CDCs is safe and feasible. The efficacy of allogeneic CDCs in HFrEF needs to be tested in larger randomised trials. © Europa Digital & Publishing 2020. All rights reserved.

The morphological changes that occur in myxomatous mitral valve disease (MMVD) involve various components, ultimately leading to the impairment of mitral valve (MV) function. In this context, intrinsic mitral annular abnormalities are increasingly recognized, such as a mitral annular disjunction (MAD), a specific anatomical abnormality whereby there is a distinct separation between the mitral annulus and the left atrial wall and the basal portion of the posterolateral left ventricular myocardium. In recent years, several studies have suggested that MAD contributes to myxomatous degeneration of the mitral leaflets, and there is growing evidence that MAD is associated with ventricular arrhythmias and sudden cardiac death. In this review, the morphological characteristics of MAD and imaging tools for diagnosis will be described, and the clinical and functional aspects of the coincidence of MAD and myxomatous MVP will be discussed.

Many college campuses are currently confronting the challenges of needing to increase mental health services to meet increased demand, and also of attending to students with higher acuity needs. The most extreme manifestations of students’ mental health problems may result in sentinel events—campus mass shootings, suicide clusters, and sexual assaults, to name a few—that may also be publicized in the media. There may also be lawsuits from parents examining culpability, as well as student complaints about inadequate or lacking mental health resources for students. College campuses have been responding by critically assessing their mental health services and, in extreme cases, completely overhauling them. In searching for best practices and consensus guidelines for student mental health care, they find this to be historically difficult, as the variation in campuses is vast, and includes private colleges, large publicly funded state colleges, community colleges, and trade/specialty schools. Even when comparing similar campuses—for example, similarly sized small liberal arts colleges—one may find that one campus does not provide any psychiatric services at all and refers students to resources in the community, whereas another campus may provide quite extensive mental health care, including psychiatric care, on campus. In a sense, each campus runs its own somewhat enclosed health-care system funded by the university and student fees, and there is immense variation in their approaches. This has made it difficult for campuses to understand the best approaches to providing student mental health care, especially in the setting of increasing need. In this chapter, we review the national trends in college mental health care. We examine the increased demand for services and potential reasons for this; the current epidemiology of student mental health problems; the systemic challenges in recruitment, retainment, and funding psychiatric services; the needs of specific populations of students; and strategies for improving access and services for students. We will also give specific examples from universities that have adopted these strategies.

Widespread adoption of dual-energy computed tomography (DECT) requires evidence it does not cause higher radiation dose than conventional single-energy CT (SECT). While a few publications involving pediatric patients exist, most have focused on small cohorts. Hence, there is still a need for studies that ascertain what radiation doses are expected in larger populations that include representative ranges of patient sizes and ages.To compare radiation dose and image quality of DECT and SECT abdominopelvic examinations in children as a function of patient size.This retrospective study included 860 children (age range: 12.3±5.3 years) who underwent contrast-enhanced abdominopelvic exams on second-generation dual-source CT in a five-year period. Two groups, SECT and DECT, consisting of 430 children each, were matched by 5 effective diameters. Volume CT dose index (CTDIDECT SSDEs were lower across all effective patient diameters compared with SECT (mean: 8.5±1.8 mGv vs. 9.3±2.0 mGv, respectively, P≤0.001). DECT CTDIIn children, regardless of effective diameter, contrast-enhanced abdominopelvic DECT can be performed with a similar or lower dose and similar image quality compared with SECT examinations.

The medicinal properties of colchicine have been recognized for centuries. Although previously used for gout and familial Mediterranean fever, its immune-modulating, anti-inflammatory, and antifibrotic effects are increasingly recognized as beneficial in the treatment of cardiovascular disorders. In this systematic review, we summarize the current evidence on colchicine's effectiveness in 1) pericarditis, 2) coronary artery disease, and 3) atrial fibrillation. We also discuss the safety, potential adverse effects, and common drug interactions that should be considered during use.

Summary The H2 capacities of a diverse set of 918,734 metal-organic frameworks (MOFs) sourced from 19 databases is predicted via machine learning (ML). Using only 7 structural features as input, ML identifies 8,282 MOFs with the potential to exceed the capacities of state-of-the-art materials. The identified MOFs are predominantly hypothetical compounds having low densities (5,300 m2 g−1), void fractions (∼0.90), and pore volumes (>3.3 cm3 g−1). The relative importance of the input features are characterized, and dependencies on the ML algorithm and training set size are quantified. The most important features for predicting H2 uptake are pore volume (for gravimetric capacity) and void fraction (for volumetric capacity). The ML models are available on the web, allowing for rapid and accurate predictions of the hydrogen capacities of MOFs from limited structural data; the simplest models require only a single crystallographic feature., Graphical abstract, Highlights • Accurate and general ML models for predicting H2 storage in MOFs are developed • The models require minimal input data that are easily derived from the MOF structure • High-capacity MOFs are identified, and capacity-structure connections are revealed • The web models (https://sorbent-ml.hymarc.org) can predict the performance of new MOFs, The bigger picture The efficient storage of hydrogen fuel remains a barrier to the adoption of fuel cell vehicles. Although many storage technologies have been proposed, adsorptive storage in metal-organic frameworks (MOFs) holds promise due to the low operating pressures, fast kinetics, reversibility, and high gravimetric densities typical of MOFs. Nevertheless, the volumetric storage densities of known MOFs are generally low; hence, new MOFs with improved volumetric performance are desired. Identifying optimal MOFs remains a challenge, however, because relatively few MOFs have been characterized experimentally, and the building-block structure of MOFs suggests that the number of possible materials is limitless. To accelerate the discovery process, this study develops machine learning models that predict the hydrogen capacity of MOFs. The models identify promising materials, clarify structure-property relations, and can be used—on the web or through an API—to predict the performance of new MOFs., The adoption of hydrogen as a low-carbon fuel has been slowed by the low energy density of H2 gas. Hydrogen adsorption in MOFs presents a pathway for storing hydrogen at the densities desired for mobile applications, such as fuel cell vehicles. Nevertheless, identifying a suitable MOF remains a challenge because the number of MOFs is essentially limitless. To accelerate the discovery of high-capacity hydrogen adsorbents, machine learning models are developed to predict hydrogen uptake across a diverse set of MOFs.

In almost all applications of concrete components, both the transport of substances such as chlorides, sulphates, acids, CO2, etc. through the pore structure into the concrete and the resulting local chemical and physical processes have a negative effect on the lifetime of the structure. Most data are actually obtained from layer-by-layer mechanical sampling of, for instance, bore dust, followed by chemical analysis. Several groups have previously demonstrated the enormous potential of LA-ICP-MS for monitoring these multi element processes both qualitatively and quantitatively and with high spatial resolution. However, there has been no fundamental investigation of laser-material interaction, aerosol particle formation, fractionation analysis or the effect of cement-specific parameters such as the water to cement (w/c) ratio on signal intensity. This paper presents the ablation mechanisms of a frequently used 213 nm quintupled Nd:YAG ns laser operating on the HCP (hardened cement paste) multi-phase system in comparison with amorphous and well-characterized NIST 612 glass. It includes energy-signal considerations, crater evaluations after multiple shots using different energy densities and aerosol structures captured on filters. The investigation determined a linear energy to signal behavior in a range of 2–6 J/cm2, while the ablation mechanism is different to common mechanisms obtained for glass or brass. The aerosol captured on the filter material displays cotton-like structures as well as defined spherical particles, which is comparable to observations made with NIST glass aerosols.

Anti-perovskite materials have recently attracted great interest as a family of non-flammable solid state electrolytes with high ionic conduction.[1] Typical solid-state electrolyte materials have temperature dependent ionic conductivity following linear Arrhenius behavior over a substantial range of temperature, corresponding to a constant activation energy Ea. However, we have discovered several anti-perovskite materials that have strong positive deviations from Arrhenius behavior, leading to rapidly rising ionic conductivities with increasing temperature. Na3OCl and Na3OBr are typical anti-perovskite compositions with atomic structure shown in Figure 1a. Strong deviations from Arrhenius (linear) behavior were observed in the temperature dependent conductivity measured by impedance spectroscopy, where Na3OCl0.5Br0.5 reaches the highest ionic conductivity with increasing temperature, as shown in Figure 1b. The structural origins of such behavior, such as change of octahedral tilt systems and order/disorder phase transition, has been investigated using multiple temperature-resolved characterization methods including synchrotron XRD, NMR, dielectric property measurements, and calorimetry, and modeled using AIMD and DFT. This work will give insight to tuning solid state electrolyte with high ionic conductivity. 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. Figure : Temperature dependent ionic conductivity and atomic model of Na-based anti-perovskites. Figure 1

As fast-ion conductors, cluster-ion anti-perovskites (APs) are attractive for potential new mechanisms of conduction whereby cation and anion motion is highly correlated [1,2]. Cluster-ion APs, like perovskites, have a framework that accommodates diverse atomic substitutions. Furthermore, the potential for cluster-ion substitution onto one or both anion sites (A and B in X3AB) provides additional compositional degrees of freedom. To identify model cluster-ion APs for understanding such conduction mechanism, we have synthesized and characterized ~20 cluster-ion APs compositions, from which Na3-x(NH2)xO1-x(BH4) has been identified as an ideal model system for understanding the correlation between cluster-ion rotation and cation transport as shown in Figure 1. Particularly, Na2(NH2)(BH4) exhibits an unusual positive deviation from ideal Arrhenius behavior indicative of a flattening of the energy landscape with increasing temperature. Concurrently, the sodium conductivity increases by 104 to 105, which is most likely due to some combination of the effects of Na vacancy introduction and NH2 and/or BH4 anion mobility. Herein, synthesis, property, and characterization of the cluster-ion APs, aimed at understanding the temperature-dependent atomistic dynamics and its effects on cation transport, will be discussed in the presentation. 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] Hong Fang and Puru Jena. Li-rich antiperovskite superionic conductors based on cluster ions. Proceedings of the National Academy of Sciences, 2017, 114, 110461. [2] Hong Fang and Puru Jena. Sodium Superionic Conductors Based on Clusters. ACS Appl. Mater. Interfaces. 2019, 11, 963-972. Figure 1

Introduction: Recently a new grading system for tricuspid regurgitation (TR) beyond severe has been proposed. However, few studies assessing the validity of the new grade of TR has been conducted. We evaluated the new grading system of TR by comparing it with patient hemodynamics and outcome. Methods: We retrospectively reviewed patients who underwent 2 dimensional echocardiography and had severe TR in 2014. According to the vena contracta width (VC) of TR jet, the patients were classified into 3 groups: VC=14mm (160,113 and 86 patients respectively). Stroke volume (SV), cardiac index (CI) and right atrial pressure (RAP) were estimated by echocardiography. Cardiac events were defined as cardiac death or admission for heart failure (HF). Results: 376 patients were diagnosed as severe TR. We excluded 15 patients on mechanical respiratory support and 2 with missing clinical data. Remaining 359 severe TR patients (75 ± 16 years, 204 (57%) female) were investigated. TR patients with VC >=14mm had significantly lower SV and CI compared to the other groups, though there was no difference in SV and CI between those with VC=14 had a significantly higher frequency of RAP >=15mmHg (Odds ratio (OR) 1.30; 95% Confidence Interval (CI), 1.01 to 3.08; p=0.047 ), though those with 11p=0.31 ) (Figure). During a follow-up period (median, 205 days; range, 36 to 1032 days), 124 (35%) patients experienced cardiac events (30 cardiac death and 94 HF admission). The Kaplan-Meier curves showed that TR patients with VC>=14 was at higher risk for cardiac events (Figure). Conclusion: TR patients with VC >=14mm showed significantly worse hemodynamics and outcome than those with VC=14mm should be considered to clinical grade of TR that is beyond severe.

BACKGROUND. How personality traits and anxiety and depressive disorders relate longitudinally has implications for etiologic research and prevention. We sought to determine how neuroticism and extraversion relate to first-onset anxiety and depressive disorders in young adults. DESIGN. An inception cohort of 489 university freshmen was followed for 6 years. METHOD. Participants self-reported personality traits using the Eysenck Personality Questionnaire, and anxiety and depressive disorders were assessed using the Diagnostic Interview Schedule. RESULTS. Baseline neuroticism predicted first-onset panic disorder, agoraphobia, generalized anxiety disorder (GAD), and major depressive disorder (MDD), while introversion predicted first-onset agoraphobia. Participants who developed panic disorder, agoraphobia, GAD, or MDD had increases in neuroticism if the disorder was current at follow-up. These effects were moderate to large. Participants who developed MDD but were in remission by follow-up had a moderate increase in neuroticism. CONCLUSIONS. High neuroticism in young adulthood is either a true risk factor, or a marker of risk, for first-onset anxiety and depressive disorders, as is low extraversion for later agoraphobia. Results suggest large neuroticism “state” effects for panic disorder, agoraphobia, and MDD, and a moderate “scar” effect from MDD. Although many clinicians and researchers regard personality traits simply as “vulnerability” factors, longitudinal analyses suggest additional complexity.

Introduction: Low-flow, low-gradient aortic stenosis (LFLG-AS) is associated with impaired left ventricular (LV) function and afterload mismatch. Indications and timing for transcatheter aortic valve replacement (TAVR) in LFLG-AS do not account for the presence of subclinical LV remodeling. We evaluated whether combining LV global longitudinal strain (GLS) and CT-derived extracellular volume (ECV), both markers of LV remodeling, provides incremental prediction of adverse outcomes in patients with LFLG-AS undergoing TAVR. Methods: We retrospectively evaluated patients with LFLG-AS undergoing TAVR in whom pre-TAVR CT-based ECV measurements were available. GLS was measured in pre-TAVR echocardiograms using speckle tracking. Cox regression analysis was performed with a primary outcome of heart failure hospitalization (HFH) or death. Four sub-groups were identified for analysis based on optimal cutoff points: Group 1 (n=64): ECV< 33 + GLS≥

This chapter highlights a range of distinct processes, both internal and interpersonal, whose linkages may form the basis of mental health. The linking of distinct elements of a system is how complex systems achieve their emergent property of optimal self-organization. Mindfulness training may be effective for creating well-being because it enhances an individual’s capacity to differentiate and link these two modes and avoid becoming trapped in either alone. The mind coordinates and balances this flow of energy and information in an optimal way through the process of integration, the linkage of differentiated parts. Linking different functional modes in the brain would be carried out through anatomic structural linkages of differentiated regions. The brain itself is connected to the rest of the nervous system extending throughout the body and is inextricably linked to the other various bodily systems, such as the immune, cardiovascular, neuromuscular, and gastrointestinal systems.