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With the increasing adoption of left atrial appendage occlusion (LAAO) procedures and the eligibility of patients for pulmonary vein isolation (PVI) post device placement, we examined the feasibility and safety of laser balloon (LB) for PVI in patients with prior LAAO.We retrospectively examined consecutive patients with paroxysmal or persistent, drug-resistant atrial fibrillation (AF) who underwent LB PVI, after Watchman FLX device implantation at Rush University Medical Center between January 2020 and December 2021.Seven patients (four persistent and three paroxysmal) with a mean age of 64 ± 11 years, predominantly male sex (86%), were included in the study. Two (29%) patients had prior cryoablation PVI with recurrence of AF. The mean CHALB PVI was safe and effective with 100% acute isolation of left-sided veins in patients with prior LAAO device.

The radio galaxy M87 is the central dominant galaxy of the Virgo Cluster. Very high-energy (VHE, ≳0.1 TeV) emission from M87 has been detected by imaging air Cherenkov telescopes. Recently, marginal evidence for VHE long-term emission has also been observed by the High Altitude Water Cherenkov Observatory, a gamma-ray and cosmic-ray detector array located in Puebla, Mexico. The mechanism that produces VHE emission in M87 remains unclear. This emission originates in its prominent jet, which has been spatially resolved from radio to X-rays. In this paper, we construct a spectral energy distribution from radio to gamma rays that is representative of the nonflaring activity of the source, and in order to explain the observed emission, we fit it with a lepto-hadronic emission model. We found that this model is able to explain nonflaring VHE emission of M87 as well as an orphan flare reported in 2005.

PurposeSevere community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.MethodsThis double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40mg loading bolus was followed by 40mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1year of follow-up.ResultsBetween January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications.ConclusionsIn patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.

Caloric restriction (CR) and Roux-en-Y Gastric Bypass (RYGB) are considered effective means of body weight control, but the mechanism by which CR and RYGB protect against high-fat diet (HFD)-induced obesity remains elusive. The browning of white adipose tissue (WAT) is a potential approach to combat obesity. Here we assess whether browning of WAT is involved in CR- and RYGB-treatment. The average size of adipocytes was determined by histological analysis. Expression of thermogenic genes in both human subjects and mice were measured by quantitative real-time PCR and immunohistochemical staining. The average size of adipocytes was bigger, while the expression of thermogenic genes such as uncoupling protein 1 (UCP1), nuclear factor erythroid-2 like 1 (NRF1) and PPARγ coactivator-1 α (PGC1α) were lower in the WAT of obese subjects when compared to lean controls. Both CR and RYGB promoted weight and fat loss. Increment of the average adipocytes size and down-regulation of thermogenic genes were significantly reversed by both CR and RYGB in the WAT of obese mice. Our findings showed that CR and RYGB significantly improved high-fat diet-induced lipid accumulation by promoting the browning of WAT.

Antibiotic resistance (AR) necessitates the discovery of new antimicrobials with alternative mechanisms of action to those employed by conventional antibiotics. One such strategy utilizes Ga3+ to target iron metabolism, a critical process for survival. Still, Ga-based therapies are generally ineffective against Gram-positive bacteria and promote Ga resistance. In response to these drawbacks, we report a lipophilic Ga complex, [Ga2L3(bpy)2] (L = 2,2'-bis(3-hydroxy-1,4-naphthoquinone; bpy = 2,2'-bipyridine)), effective against drug-resistant Pseudomonas aeruginosa (DRPA; minimum inhibitory concentration, MIC = 10 μM = 14.8 μg/mL) and methicillin-resistant Staphylococcus aureus (MRSA, MIC = 100 μM = 148 μg/mL) without iron-limited conditions. Importantly, [Ga2L3(bpy)2] shows noticeably delayed and decreased resistance in both MRSA and DRPA, with only 8× MIC in DRPA and none in MRSA after 30 passages. This is likely due to the dual mode of action afforded by Ga (disruption of iron metabolism) and the ligand (reactive oxygen species production). Overall, [Ga2L3(bpy)2] demonstrates the utility of lipophilic metal complexes with multiple modes of action in combatting AR in Gram-positive and Gram-negative bacteria.

Empirical evidence suggests that both leisure time and medical care are important for maintaining health. We develop a general equilibrium macroeconomic model in which taxation is a key determinant of the composition of these two inputs in the endogenous accumulation of health capital. In our model, higher taxes lead to using relatively more leisure time and less medical care in maintaining health. We find that difference in taxation between the US and Europe can account for a large fraction of their difference in health expenditure-GDP ratio and almost all of their difference in time input for health production.

BACKGROUND Radiofrequency (RF) ablation with half-normal saline (HNS) has shown promise as a bail-out strategy following failed ventricular tachycardia ablation using standard approaches. OBJECTIVE To use a novel infrared thermal imaging (ITI) model to evaluate biophysical and lesion characteristics during RF ablation using normal saline (NS) and HNS irrigation. METHODS Left ventricular strips of myocardium were excised from fresh porcine hearts. RF ablation was performed using an open-irrigated ablation catheter (Thermocool ST/SF) with NS (n = 75) and HNS (n = 75) irrigation using different power settings (40/50 W), RF durations (30/60 s), contact force of 10-15 g, and flow rate of 15 ml/min. RF lesions were recorded using an infrared thermal camera and border zone, lethal, 100° isotherms were matched with necrotic borders after 2% triphenyltetrazolium chloride staining. Lesion dimensions and isotherms (mm2 ) were measured. RESULTS In total, 150 lesions were delivered. HNS lesions were deeper (6.4 ± 1.1 vs. 5.7 ±0.8 mm; p = .03), and larger in volume (633 ± 153 vs. 468 ± 107 mm3 ; p = .007) than NS lesions. Steam pops (SPs) occurred during 19/75 lesions (25%) in the NS group and 32/75 lesions (43%) in the HNS group (p = .34). Lethal (57.8 ± 6.5 vs. 36.0 ± 3.9 mm2 ; p = .001) and 100°C isotherm areas (16.9 ± 6.9 vs. 3.8 ± 4.2 mm2 ; p = .003) areas were larger and were reached earlier in the HNS group. CONCLUSIONS RFA using HNS created larger lesions than NS irrigation but led to more frequent SPs. The presence of earlier lethal isotherms and temperature rises above 100°C on ITI suggest a potentially narrower therapeutic-safety window with HNS.

Analysis of earthquake locations and centroid moment tensors (CMTs) is critical in assessing seismogenic structures and connecting earthquakes to anthropogenic activities. The objective of this study was to gain insights into the seismotectonics of the Eagle Ford Shale play (EF), southern Texas, through relative relocation of earthquakes, assessment of CMT solutions, and investigation of the background stress field. Using Texas Seismological Network (TexNet) data from 2017 through 2019, we were able to relocate 326 earthquakes and obtain CMT solutions for 37 ML≥2.0 earthquakes. These earthquakes are located in the sedimentary basin and uppermost crust, with depths ranging from 2 to 10 km. The earthquake groups in the northeastern EF are linearly distributed along the Karnes fault zone, whereas the southern and western groups are spatially scattered around mapped or unmapped faults. CMT solutions identified 32 normal fault earthquakes and five strike-slip earthquakes. The orientation of the fault plane of most normal fault earthquakes is southwest–northeast, whereas the possible fault plane of the strike-slip fault is from north-northwest to south-southeast, which is roughly perpendicular to the normal faults. Normal and strike-slip faults in the EF are of high dip angles, with the dip angles of the most faults ranging from 60° to 80°. Stress inversion results show that the major orientation of maximum horizontal stress (SHmax) is southwest–northeast, with minor local stress-field rotations. We further estimated earthquake energy release in the EF region using moment magnitude from the CMT solutions, and the cumulative earthquake energy release curve reveals three notable increases in cumulative seismic moment, which occurred in January–July 2018 and January–March 2019, and May–August 2019. Whether these energy releases were caused by anthropogenic activities is a matter for further investigation.

Natural fragmentation of steel cylinders with different charge sizes is investigated, and the correlation of different cylinders is proposed. The Mott fragment distribution has some obvious shortcomings, including the difficulty of accurately determining the number of fragments. Besides, there is no unified and convenient method to describe the fragmentation behavior of shells with different structures. The results show that the fragmentation behavior of the cylinder is self-similar statistically and can be characterized by a new integrated linear formula $$C_L = a + b (C / M)$$ . Due to the existence of the end face and the charge clearance, the fragmentation performance of the cylinder is reduced to a constant value, and the effect of the wall thickness is small. The influence of the end face and charge clearance on fragmentation is investigated by 3D simulations, and the numerical results ensure good validation of the experimental data.

Emergency ultrasound (EUS) is a critical component of emergency medicine (EM) resident education. Currently, there is no consensus list of competencies for EUS training, and graduating residents have varying levels of skill and comfort. The objective of this study was to define a widely accepted comprehensive list of EUS competencies for graduating EM residents through a modified Delphi method.We developed a list of EUS applications through a comprehensive literature search, the American College of Emergency Physicians list of core EUS benchmarks, and the Council of Emergency Medicine Residency-Academy of Emergency Ultrasound consensus document. We assembled a multi-institutional expert panel including 15 faculty members from diverse practice environments and geographical regions. The panel voted on the list of competencies through two rounds of a modified Delphi process using a modified Likert scale (1 = not at all important, 5 = very important) to determine levels of agreement for each application-with revisions occurring between the two rounds. High agreement for consensus was set at80%.Fifteen of 15 panelists completed the first-round survey (100%) that included 359 topics related to EUS. After the first round, 195 applications achieved high agreement, four applications achieved medium agreement, and 164 applications achieved low agreement. After the discussion, we removed three questions and added 13 questions. Fifteen of 15 panelists completed the second round of the survey (100%) with 209 of the 369 applications achieving consensus.Our final list represents expert opinion on EUS competencies for graduating EM residents. We hope to use this consensus list to implement a more consistent EUS curriculum for graduating EM residents and to standardize EUS training across EM residency programs.

BackgroundOlder adults and persons with medical co-morbidities are at increased risk for severe COVID-19. Several pharmacotherapies demonstrated to reduce the risk of COVID-19-related hospitalization and death have been authorized for use. We describe factors associated with receipt of outpatient COVID-19 pharmacotherapies in the Veterans Health Administration.MethodsWe conducted a retrospective cohort study among Veterans with risk factors for severe COVID-19 who tested positive for SARS-CoV-2 during January and February 2022. We compared receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir plus ritonavir, molnupiravir, or remdesivir versus no antiviral or monoclonal antibody treatment according to demographic characteristics, place of residence, underlying medical conditions, and COVID-19 vaccination using multivariable logistic regression.ResultsDuring January and February 2022, 16,546 courses of sotrovimab, nirmatrelvir, and molnupiravir were allocated across the Veterans Health Administration. Among 111,717 Veterans testing positive for SARS-CoV-2, 4,233 (3.8%) received any COVID-19 pharmacotherapy, including 2,870 of 92,396 (3.1%) in January and 1,363 of 19,321 (7.1%) in February. Among a subset of 56,206 Veterans with documented COVID-19-related symptoms in the 30 days preceding positive SARS-CoV-2 test, 3,079 of 53,206 (5.5%) received any COVID-19 pharmacotherapy. Untreated Veterans had a median age of 60 years (interquartile range [IQR] 46-71 years) and median 3 underlying medical conditions (IQR 2-5). Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR] 1.66, 95% confidence interval [CI] 1.52-1.80, 65-74 versus 50-64 years; aOR 1.67, 95% CI 1.53-1.84 ≥75 versus 50-64 years) and have a higher number of underlying conditions (aOR 1.63, 95% CI 1.48-1.79, 3-4 versus 1-2 conditions; aOR 2.17, 95% CI 1.98-2.39, ≥5 versus 1-2 conditions). Persons of Black versus White race (aOR 0.65, 95% CI 0.60-0.72) and well as persons of Hispanic ethnicity (aOR 0.88, 95% CI 0.77-0.99) were less likely to receive treatment.Conclusions and RelevanceAlthough supply of outpatient COVID-19 pharmacotherapies during January and February 2022 was limited, prescription of these pharmacotherapies was underutilized, consistent with early national patterns in dispensing. Racial and ethnic minorities were less likely to receive any pharmacotherapy.

The High Altitude Water Cherenkov (HAWC) gamma-ray observatory observes atmospheric showers produced by incident gamma rays and cosmic rays with energy from 300 GeV to more than 100 TeV. A crucial phase in analyzing gamma-ray sources using ground-based gamma-ray detectors like HAWC is to identify the showers produced by gamma rays or hadrons. The HAWC observatory records roughly 25,000 events per second, with hadrons representing the vast majority ($>99.9\%$) of these events. The standard gamma/hadron separation technique in HAWC uses a simple rectangular cut involving only two parameters. This work describes the implementation of more sophisticated gamma/hadron separation techniques, via machine learning methods (boosted decision trees and neural networks), and summarizes the resulting improvements in gamma/hadron separation obtained in HAWC., 35 pages, 9 figures, published in Nuclear Instruments and Methods in Physics Research Section A

In patients with cardiomyopathy, radiofrequency catheter ablation (CA) for ventricular tachycardia (VT) is an adjunctive and alternative treatment option to long-term anti-arrhythmic drug therapy. We sought to compare CA with medical therapy for the management of VT in patients with ischemic and non-ischemic cardiomyopathies.MEDLINE, Cochrane, and ClinicalTrials.gov databases were evaluated for relevant studies.Eleven studies with 2126 adult patients were included (711 in CA, 1415 in medical therapy). In the randomized controlled trial (RCT) analysis, CA reduced risk of recurrent VT (risk ratio (RR) 0.79 [95% CI 0.67 to 0.93], p = 0.005), ICD shocks (RR 0.64 [95% CI 0.45 to 0.89] p = 0.008), and cardiac hospitalizations (RR 0.76 [95% CI 0.63 to 0.92] p = 0.005). There was no difference in all-cause mortality (RR 0.94, p = 0.71). In combined RCT and observational study analysis, there was a trend for reduction in all-cause mortality (RR 0.75 [95% CI 0.55 to 1.02] p = 0.07). In subgroup analysis of studies with mean left ventricular ejection fraction (LVEF) 35%, CA demonstrated reduction in mortality (RR 0.71, p = 0.004), ICD shocks (RR 0.63, p = 0.03), VT recurrence (RR 0.76, p = 0.004), and cardiac hospitalizations (RR 0.75, p = 0.02). The subgroup of early CA prior to ICD shocks demonstrated reduction in ICD shocks (RR 0.57, p 0.001) and VT recurrence (RR 0.74, p = 0.01).CA for VT demonstrated a lower risk of VT recurrence, ICD shocks, and hospitalization in comparison to medical therapy. The subgroups of early CA and LVEF 35% demonstrated better outcomes.

The “signatures” of rare earth elements (REEs) in fossil bones are used as proxies for provenance, taphonomy, and palaeoenvironment evaluations. However, measuring the content of REEs requires several steps, which is highly time-consuming. An online detection approach involving sequential leaching with mass spectrometry was developed to quantify REEs in dinosaur (Yimenosaurus species) bone. Five fractions of REEs (water-soluble, exchangeable, reducible, oxidizable, and crystalline) could be detected sequentially within 1 h and consume only 1 mg of sample. Most importantly, compared with traditional methods, our method was more accurate, faster (1 h), consumed less sample (1 mg), and could provide more information regarding the spatial distribution of REEs. Our method allowed rapid analyses of REEs in different phases and had good sensitivity and accuracy.

Although a biologically nonessential element in living organisms, aluminum is notably nontoxic to eukaryotic cells and has a venerable history of medicinal use. We demonstrate that polyethylene glycol-coated γ-alumina nanoparticles (Al2O3-NPs) with an average size of 15 nm prepared from a commercial bulk γ-alumina (γ-Al2O3) via the top-down sonication technique exhibit antibacterial activity that is comparable to that of AgNPs against both the Gram-negative drug-susceptible Pseudomonas aeruginosa (DSPA) and multidrug-resistant Pseudomonas aeruginosa (DRPA) bacteria, while the antibacterial activity of such Al2O3-NPs considerably surpasses that of AgNPs against both the Gram-positive methicillin-susceptible Staphylococcus aureus (DSSA) and methicillin-resistant Staphylococcus aureus (MRSA) bacteria. We also demonstrate that the DSPA bacteria sequentially exposed to Al2O3-NPs for 30 days show no indication of resistance development. Furthermore, such Al2O3-NPs can completely overcome the drug resistance developed in the conventional antibiotic ciprofloxacin-resistant and AgNP-resistant mutants without developing Al resistance.

Recent theoretical papers argue that countries can insulate themselves from volatile world capital flows by using a variable tax on foreign capital as an instrument of monetary policy. But empirical papers argue that we rarely observe these cyclical capital flow taxes used in practice. We construct a small open economy model where the central bank engages in sterilized foreign exchange intervention. When private agents freely trade foreign bonds, sterilized intervention has no effect. But we prove that when frictions prevent the free trade in foreign bonds, optimal sterilized foreign exchange intervention is equivalent to an optimal tax on foreign capital. The model is then calibrated to match the levels of capital account restrictions that we observe in the data. For levels of capital account openness that we observe in many emerging market economies, a variable tax on capital flows is a close approximation for sterilized foreign exchange intervention.