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BACKGROUND: Heart transplantation (HTx) after donation after circulatory death (DCD) is an expanding practice but is associated with increased warm ischemic time. The impact of DCD HTx on cardiac mechanics and myocardial fibrosis has not been reported. We aimed to compare cardiac mechanics and myocardial fibrosis using cardiovascular magnetic resonance (CMR) imaging in donation after brain death (DBD) and DCD HTx recipients and healthy controls. METHODS AND RESULTS: Consecutive HTx recipients between March 2015 and March 2021 who underwent routine surveillance CMR imaging were included. Cardiac mechanics were assessed using CMR feature tracking to compute global longitudinal strain, global circumferential strain, and right ventricular free-wall longitudinal myocardial strain. Fibrosis was assessed using late gadolinium enhancement imaging and estimation of extracellular volume. There were 82 (DBD n = 42, DCD n = 40) HTx recipients (aged 53 years, interquartile range 41-59 years, 24% female) who underwent CMR imaging at median of 9 months (interquartile range 6-14 months) after transplantation. HTx recipients had increased extracellular volume (29.7 ± 3.6%) compared with normal ranges (25.9%, interquartile range 25.4-26.5). Myocardial strain was impaired after transplantation compared with controls (global longitudinal strain -12.6 ± 3.1% vs -17.2 ± 1.8%, P < .0001; global circumferential strain -16.9 ± 3.1% vs -19.2 ± 2.0%, P = .002; right ventricular free-wall longitudinal strain -15.7 ± 4.5% vs -21.6 ± 4.7%, P < .0001). There were no differences in fibrosis burden (extracellular volume 30.6 ± 4.4% vs 29.2 ± 3.2%; P = .39) or cardiac mechanics (global longitudinal strain -13.1 ± 3.0% vs -12.1 ± 3.1%, P = .14; global circumferential strain -17.3 ± 2.9% vs -16.6 ± 3.1%, P = .27; right ventricular free-wall longitudinal strain -15.9 ± 4.9% vs -15.5 ± 4.1%, P = .71) between DCD and DBD HTx. CONCLUSIONS: HTx recipients have impaired cardiac mechanics compared with controls, with increased myocardial fibrosis. There were no differences in early CMR imaging characteristics between DBD and DCD heart transplants, providing further evidence that DCD and DBD HTx outcomes are comparable.

Background Parkinson's disease (PD) caregivers, particularly in Latin America, may experience high levels of affiliate stigma due to their association with a person having a disability. The most common measure used of this construct in the literature, the Affiliate Stigma Scale, was validated using non-standard and questionable methods. Objective The purpose of this study was to investigate the factor structure and psychometric properties of the Spanish version of the Affiliate Stigma Scale with PD caregivers in Mexico using more widely accepted psychometric approaches including confirmatory and exploratory factor analyses (confirmatory factor analyses (CFAs) and exploratory factor analyses (EFAs)). Methods A sample of 148 PD caregivers from Mexico completed this measure, as well as indices of caregiver burden and anxiety. Results Initial CFAs revealed that the data did not fit either the originally proposed one-factor or three-factor structures. An EFA was then conducted which was unable to discern any factor structure. Upon instituting a stepwise removal alpha-if-item-deleted process, a 5-item Affiliate Stigma Scale Spanish Short Form was retained with an adequate Cronbach's alpha, good convergent validity, and a Short Form CFA generally indicating adequate fit. Conclusions The new Spanish Affiliate Stigma Scale Short Form holds promise for more appropriately measuring affiliate stigma likely in general but particularly in Spanish and among PD caregivers. The Short Form can assist not only in assessing levels of caregiver affiliate stigma, but in creating novel interventions to help support caregivers and decrease stigma.

BACKGROUND: Research has found that Hispanics with traumatic brain injury (TBI) have reduced functional outcomes compared to non-Hispanic Whites, including lower probabilities of post-injury employment. However, previous studies were cross-sectional, combined racial/ethnic minority groups, and did not examine the factors that predict return to work of Hispanics longitudinally. OBJECTIVE: To determine the demographic and injury-related predictors of employment probability trajectories during the first 10 years after TBI. METHODS: 1,346 Hispanics in the TBI Model Systems Database were included. Hierarchical linear modeling was used to examine baseline predictors of employment probability trajectories across this time period. RESULTS: Employment probability demonstrated a quadratic movement over time, with an initial increase followed by a plateau or slight decrease. Hispanics with TBI had higher employment probability trajectories if they had been younger at the time of injury, spent less time in posttraumatic amnesia, had greater years of education, had been employed at the time of injury, had higher annual earnings at the time of injury, and had experienced a non-violent mechanism of injury. CONCLUSION: Culturally adapted treatment programs with a focus on early intervention incorporating vocational rehabilitation and employment programs for Hispanics with TBI who present with these risk factors are needed.

Differentiation of multipotent mesenchymal stem cells (MSCs) into bone-forming osteoblasts requires strict coordination of transcriptional pathways. Aryl hydrocarbon receptor ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have been shown to alter osteoblast differentiation in vitro and bone formation in multiple developmental in vivo models. The goal of the present study was to establish a global transcriptomic landscape during early, intermediate, and apical stages of osteogenic differentiation in vitro in response to TCDD exposure. Human bone-derived mesenchymal stem cells (hBMSCs) were cultured in growth media (GM), osteogenic differentiation media (ODM), or ODM containing 10 nM TCDD (ODM + TCDD), thus enabling a comparison of the transcriptomic profiles of undifferentiated, differentiated, and differentiated-TCDD-exposed hBMSCs, respectively. In this test system, exposure to TCDD attenuated the differentiation of hBMSCs into osteoblasts as evidenced by reduced alkaline phosphatase activity and mineralization. At various timepoints, we observed altered expression of genes that play a role in the Wnt, fibroblast growth factor, bone morphogenetic protein/transforming growth factor beta developmental pathways, as well as pathways related to extracellular matrix organization and deposition. Reconstruction of gene regulatory networks with the interactive dynamic regulatory event miner (iDREM) analysis revealed modulation of transcription factors (TFs) including POLR3G, NR4A1, RDBP, GTF2B, POU2F2, and ZEB1, which may putatively influence osteoblast differentiation and the requisite deposition and mineralization of bone extracellular matrix. We demonstrate that the combination of RNA-Seq data in conjunction with the iDREM regulatory model captures the transcriptional dynamics underlying MSC differentiation under different conditions in vitro. Model predictions are consistent with existing knowledge and provide a new tool to identify novel pathways and TFs that may facilitate a better understanding of the osteoblast differentiation process, perturbation by exogenous agents, and potential intervention strategies targeting those specific pathways.

To elucidate challenges to timely hospital discharge of children in foster care (CFC).Inpatient providers with prior experience caring for CFC were recruited from 6 mid-Atlantic hospitals. Semi-structured interviews were conducted to explore provider experience discharging CFC. Conventional content analysis was applied to interview transcripts with Dedoose software.Interviews were completed with 15 MDs/NPs, 11 RNs, 10 social workers, and 2 case managers. Participants explained that delayed discharge is the norm for CFC, especially for those entering new foster care placements. Participants detailed challenges to efficiently discharging CFC, which were categorized into 3 themes: 1) Waiting for discharge disposition: Providers' ability to proceed with discharge planning is contingent on procedural steps (eg, court decisions) needed to determine disposition (eg, entering new foster care placement); 2) Medically cleared, but no place to go: Participants report placement searches are often not initiated by child welfare until the child is medically cleared. Lack of available, appropriate foster care placements delays discharge, particularly for children with complex medical or behavioral diagnoses; 3) Coordinating for a safe discharge: Establishing a safe discharge for CFC involves meticulous discharge planning, foster parent training, and multidisciplinary team communication/coordination.Delayed discharge for CFC is multifactorial, yet often predictable. There are modifiable factors identified that can be addressed to promote timely hospital discharge and prevent medically unnecessary hospital days, benefitting patients in foster care and the hospital system.

This study examined demographic and injury-related predictors of cognitive and motor functional independence in Hispanics with TBI at years 1, 2, 5, and 10 after hospital discharge.Hispanic participants (n = 1,360) from the TBI Model Systems Study were included in if they had at least one Functional Independence Measure (FIM) Cognitive and Motor score at any time point (years 1, 2, 5, or 10). Hierarchical linear modeling was used to examine baseline predictors of FIM Cognitive and Motor trajectories across this time period.FIM Cognitive trajectories showed a quadratic movement (initial increase followed by a plateau or slight decrease), whereas FIM Motor trajectories showed a cubic movement (initial increase, followed by a plateau, then another increase). Higher FIM Cognitive trajectories were predicted by younger age, shorter length of posttraumatic amnesia (PTA), higher education, and having experienced a non-violent mechanism of injury. Higher FIM Motor trajectories were predicted by younger age, shorter PTA, and a non-violent mechanism of injury.The baseline predictors of functional trajectories identified may help create tailored, evidence-based rehabilitation interventions along the continuum of recovery during the first 10 years for Hispanics with TBI at-risk for reduced functional outcomes.

The development of oxidant-free gold-catalyzed cross coupling reactions involving aryl halides have been hamstrung by the lack of gold catalysts capable of performing oxidative addition at Au(I) centers. Herein, we report the development of novel tricoordinate Au(I) catalysts supported by N,N-bidentate ligands and ligated by phosphine or arsine ligands for C-H functionalization without external oxidants to form biaryls with no homocoupling. The unsymmetrical character of the Au(I) catalyst is critical to facilitating this necessary orthogonal transformation. This study unveils yet another potential of Au(I) catalysis in biaryl synthesis.

To assess stability and degradation over time, of methadone alone, and mixed with lidocaine and ketamine, using various diluents and storage conditions.Solutions of methadone diluted in 0.9% NaCl, and methadone-lidocaine-ketamine diluted in 0.9% NaCl or Hartmann's solution, and stored at room temperature with exposure to light, or refrigerated at 4°C and protected from light, were maintained over 10 days. Chemical stability was determined using liquid chromatography immediately after preparation and following 4, 24, 48, 96 and 240 hours of storage. Physical stability of the solutions was evaluated by visual examination and absorbance of ultraviolet/visible light. A linear model assessed the impact of different diluent solutions and storage conditions on drug degradation over time.There was no evidence of physicochemical incompatibility for any solution. Methadone concentration, when diluted alone or in methadone-lidocaine-ketamine with Hartmann's solution at 4°C, did not decline over time. Ketamine and lidocaine decreased to a similar extent over time, regardless of the diluent used or storage method, while methadone in methadone-lidocaine-ketamine diluted with 0.9% NaCl or with Hartmann's solution at room temperature exposed to light, also declined over time; however, all three methadone-lidocaine-ketamine components retained acceptable stability (10% degradation) for at least 48 hours following preparation, irrespective of diluent or storage conditions.Regardless of the diluent or storage method, methadone-lidocaine-ketamine solutions degrade over time, but this only becomes clinically significant after 48 hours. Solutions of 1 mg/ml methadone in 0.9% NaCl are stable for at least 10 days under storage conditions likely to be encountered in general practice.

The physical basis and application of the fundamental relationship governing the balance and utilization of available energy for a chemical rocket operating within the atmosphere are described. The...

This study examined the relations among burn stigma, quality of life, resilience, and life satisfaction, hypothesizing that higher stigma and lower burn-related quality of life would lead to lower life satisfaction; however, resilience would moderate this relation. A sample of 89 participants was recruited from an outpatient clinic of a burn center in a critical care hospital. Participants completed a battery of measures assessing these constructs. Results suggested that burn stigma was associated with reduced life satisfaction after accounting for other variables. Multiple regression models found that burn stigma predicted both affect and body image but not interpersonal relationship quality or sexuality. Interpersonal relationship quality, sexuality, affect, and body image all predicted life satisfaction. Both affect and body image partially accounted for the relation between stigma and life satisfaction, and resilience accounted for the relation between stigma and affect. Findings reinforce previous literature that has shown a relationship between stigma and life satisfaction but also emphasizes the role of resilience and burn-related quality of life. Individuals who experience a burn injury may have innate resilience abilities, which allow them to bounce back from stressors; thus, resilience can be a targeted strength to bootstrap in order to improve adjustment outcomes.

One-carbon metabolism, including the folate cycle, has a crucial role in fetal development though its molecular function is complex and unclear. The hypomorphicMtrrgtallele is known to disrupt one-carbon metabolism, and thus methyl group availability, leading to several developmental phenotypes (e.g., neural tube closure defects, fetal growth anomalies). Remarkably, previous studies showed that some of the phenotypes were transgenerationally inherited. Here, we explored the genome-wide epigenetic impact of one-carbon metabolism in placentas associated with fetal growth phenotypes and determined whether specific DNA methylation changes were inherited. Firstly, methylome analysis ofMtrrgt/gthomozygous placentas revealed genome-wide epigenetic instability. Several DMRs were identified including at theCxcl1gene promoter and at theEn2gene locus, which may have phenotypic implications. Importantly, we discovered hypomethylation and ectopic expression of a subset of ERV elements throughout the genome ofMtrrgt/gtplacentas with broad implications for genomic stability. Next, we determined that sperm DMRs in males from theMtrrgtmodel were reprogrammed in the placenta with little evidence of direct or transgenerational germline DMR inheritance. However, some sperm DMRs were associated with placental gene misexpression despite normalisation of DNA methylation, suggesting the inheritance of an alternative epigenetic mechanism. Integration of published histone ChIP-seq datasets with sperm methylome and placenta transcriptome data from theMtrrgtmodel point towards H3K4me3 deposition at key loci suggesting that histone modifications might play a role in epigenetic inheritance in this context. This study sheds light on the mechanistic complexities of one-carbon metabolism in development and epigenetic inheritance.

Purpose:Napabucasin (2-acetylfuro-1,4-naphthoquinone or BBI-608) is a small molecule currently being clinically evaluated in various cancer types. It has mostly been recognized for its ability to inhibit STAT3 signaling. However, based on its chemical structure, we hypothesized that napabucasin is a substrate for intracellular oxidoreductases and therefore may exert its anticancer effect through redox cycling, resulting in reactive oxygen species (ROS) production and cell death.Experimental Design:Binding of napabucasin to NAD(P)H:quinone oxidoreductase-1 (NQO1), and other oxidoreductases, was measured. Pancreatic cancer cell lines were treated with napabucasin, and cell survival, ROS generation, DNA damage, transcriptomic changes, and alterations in STAT3 activation were assayed in vitro and in vivo. Genetic knockout or pharmacologic inhibition with dicoumarol was used to evaluate the dependency on NQO1.Results:Napabucasin was found to bind with high affinity to NQO1 and to a lesser degree to cytochrome P450 oxidoreductase (POR). Treatment resulted in marked induction of ROS and DNA damage with an NQO1- and ROS-dependent decrease in STAT3 phosphorylation. Differential cytotoxic effects were observed, where NQO1-expressing cells generating cytotoxic levels of ROS at low napabucasin concentrations were more sensitive. Cells with low or no baseline NQO1 expression also produced ROS in response to napabucasin, albeit to a lesser extent, through the one-electron reductase POR.Conclusions:Napabucasin is bioactivated by NQO1, and to a lesser degree by POR, resulting in futile redox cycling and ROS generation. The increased ROS levels result in DNA damage and multiple intracellular changes, one of which is a reduction in STAT3 phosphorylation.

Supplementary Figures 1,2,3,4,5,6,7

Table listing the differentially expressed genes between napabucasin treated cells compared to DMSO as vehicle control

Supplementary Figure Legends

Supplementary Methods, Figures 1-6, Tables A-C from Targeting Activin Receptor-Like Kinase 1 Inhibits Angiogenesis and Tumorigenesis through a Mechanism of Action Complementary to Anti-VEGF Therapies

PDF file - 137K, Detailed relationship between the PAP parameter derived through the image-guided model with the classical parameters of solute transport coefficient, clearance, and 30 minute albumin clearance (Cl30).

PDF file - 51K, Representative biodistribution of tissues 48 hours after nanoparticle injection (N=8). Accumulation was significantly greater for insonified tumors (p

Halide-formic acid complexes have been studied utilising a combined experimental and theoretical approach. Formic acid exists as two conformers, distinguished by the relative rotation about the C-OH bond. Computational investigation of the formic acid isomerisation reaction between the two conformers has revealed the ability of halide anions to catalyse the formation of, and preferentially stabilise, the higher energy conformer. Anion photoelectron spectroscopy has been used to study the halide-formic acid complexes, with the experimental vertical detachment energies compared with simulated photodetachment energies with respect to halide complexes with both formic acid conformers. The existence of experimental spectral features associated with halide complexes of the higher energy formic acid confomer confirms

Anion photoelectron spectroscopy has been used to determine the electron binding energies of the X−⋯C3H6 (X = Cl, Br, I) complexes.

Summary Background Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov , NCT02509494 . Findings From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children. Funding Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.

Sarcopenia, loss of muscle mass and strength, has been associated with more frequent complications after esophagectomy. This study compared hand-grip strength, muscle mass, and intramuscular adipose tissue as predictors of postoperative outcomes and mortality after esophagectomy. Minimally invasive esophagectomy was performed on 175 patients with esophageal cancer. Skeletal muscle index and skeletal muscle density were derived from preoperative CTs. Hand-grip strength was measured using dynamometer. Univariate and multivariable analyses were performed. Preoperative hand-grip strength was normal in 91 (52%), intermediate in 43 (25%), and weak in 41 (23%) patients. Hand-grip strength was significantly correlated with both skeletal muscle index and skeletal muscle density. Postoperative pneumonia occurred in 8/41 (20%) patients with weak strength compared to 4/91 (4%) with normal strength (p = 0.006; Cochran-Armitage Test). Prolonged postoperative ventilation occurred in 11/41 (27%) patients with weak strength compared to 11/91 (12%) with normal strength (p = 0.036). Median length of stay was 9 days in patients with weak strength compared to 7 days for those with normal strength (p = 0.005; Kruskal–Wallis Test). Discharge to non-home location occurred in 15/41 (37%) with weak strength compared to 8/91 (9%) with normal strength (p

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Grid-forming inverter-based autonomous microgrids present new operational challenges as the stabilizing rotational inertia of synchronous machines is absent. The design of efficient control policies for grid-forming inverters is, however, a nontrivial problem where multiple performance objectives need to be satisfied, including voltage/frequency regulation, current limiting capabilities, and active power sharing and a scalable operation. We propose, in this article, a novel control architecture for frequency and voltage control, which allows current limitation via an inner loop, active power sharing via a distributed secondary control policy, and scalability by satisfying a passivity property. In particular, the frequency controller employs the inverter output current and angle to provide an angle droop-like policy, which improves its stability properties. This also allows us to incorporate a secondary control policy for which we provide an analytical stability result, which takes line conductances into account (in contrast to the lossless line assumptions in the literature). The distinctive feature of the voltage control scheme is that it has a double-loop structure that uses the dc voltage in the feedback control policy to implement a power-balancing strategy to improve performance. The performance of the control policy is illustrated via simulations with detailed nonlinear models in a realistic setting.

Diverse emergent correlated electron phenomena have been observed in twisted graphene layers due to electronic interactions with the moir\'e superlattice potential. Many electronic structure predictions have been reported exploring this new field, but with few momentum-resolved electronic structure measurements to test them. Here we use angle-resolved photoemission spectroscopy (ARPES) to study the twist-dependent ($1^\circ < \theta < 8^\circ$) electronic band structure of few-layer graphenes, including twisted bilayer, monolayer-on-bilayer, and double-bilayer graphene (tDBG). Direct comparison is made between experiment and theory, using a hybrid $\textbf{k}\cdot\textbf{p}$ model for interlayer coupling and implementing photon-energy-dependent phase shifts for photo-electrons from consecutive layers to simulate ARPES spectra. Quantitative agreement between experiment and theory is found across twist angles, stacking geometries, and back-gate voltages, validating the models and revealing displacement field induced gap openings in twisted graphenes. However, for tDBG at $\theta=1.5\pm0.2^\circ$, close to the predicted magic-angle of $\theta=1.3^\circ$, a flat band is found near the Fermi-level with measured bandwidth of $E_w = 31\pm5$ meV. Analysis of the gap between the flat band and the next valence band shows significant deviations between experiment ($\Delta_h=46\pm5$meV) and the theoretical model ($\Delta_h=5$meV), indicative of the importance of lattice relaxation in this regime.

ImportanceThe COVID-19 pandemic challenged the financial solvency of hospitals, yet there is limited evidence examining hospital financial performance through the first 15 months of the pandemic.ObjectiveTo assess the financial outcomes associated with the COVID-19 pandemic in California hospitals.Design, Setting, and ParticipantsThis cross-sectional study tracked the financial performance of 348 hospitals in California using Hospital Quarterly Financial and Utilization Data from the State of California Office of Statewide Health Planning and Development. Hospital financial performance was examined from January 2019 to June 2021 for all hospitals in aggregate and by safety-net status.ExposuresPre–COVID-19 financial outcomes vs COVID-19 period outcomes.Main Outcomes and MeasuresQuarterly revenues, expenses, and profits.ResultsIn 348 California hospitals, hospital financial performance was highly variable during the COVID-19 pandemic. Losses were reduced by COVID-19 relief funding and strong equities market performance starting in the second quarter of 2020. Non–safety net hospitals maintained positive operating margins throughout the pandemic, while safety-net hospitals experienced large losses. Between the first quarter of 2020 and the second quarter of 2021, California safety-net hospitals’ net operating losses were more than $3.2 billion.Conclusions and RelevanceIn this cross-sectional study of California hospitals, hospital financial performance was tracked between the first quarter of 2019 and the second quarter of 2021. Although hospitals experienced reduced profits between January 2020 and June 2021, the interventions of government assistance programs were able to mitigate more detrimental fiscal consequences. When compared with non–safety net hospitals, safety-net hospitals were confronted with more concentrated financial losses.

Introduction Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. Recent development has seen the introduction of non-invasively computed PV loops from cardiovascular magnetic resonance (CMR) volumetry and a brachial blood pressure measurement. The approach combines LV volumes with a time-varying elastance function to compute time-resolved LV pressures and was validated on invasive pressure data from a porcine model. The method is readily implemented using standard CMR sequences and provides measures of hemodynamic parameters including stroke work, myocardial efficiency, and contractile state. However, the method remains to be validated in patients using invasive left ventricular pressure recordings. Purpose To validate for the first time in human patients the performance of non-invasively computed PV loops against invasive measures. Methods Four heart failure patients underwent two subsequent sessions of CMR cine imaging and simultaneous brachial blood pressure measurement, with intravenous administration of two different vasoactive drugs, resulting in two different haemodynamic states for each patient. LV catheterization was then conducted with repeat administration of the same infusions. Pressure-volume loops were computed from CMR volumes combined with 1) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, and 2) invasive pressures averaged from multiple sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis. Results Figure 1 shows non-invasively derived PV loop parameters compared to invasive data. The non-invasive method demonstrated strong correlations and low bias for stroke work (R2=0.97, bias 4.6%, p Conclusions Pressure-volume loops can be precisely and accurately computed from cardiovascular magnetic resonance imaging and brachial cuff blood pressure in humans, and is ready for use in research applications. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung Foundation

Background Cervical cancer caused by human papillomavirus (HPV) is the most frequent cancer in women in many low-income countries.Tanzania implemented a national HPV vaccination program in 2018 using a two-dose quadrivalent HPV vaccine. This study aimed to (1) estimate financial and economic costs of a two-dose vaccination program based on experiences with the national vaccination program, (2) estimate costs of a one-dose vaccination schedule to enable future cost-effectiveness analyses, and (3) assess the effect of alternative assumptions for future vaccination coverage rates on estimated costs of vaccination. Methods The WHO Cervical Cancer Prevention and Control Costing (C4P) tool was used to estimate the incremental costs of the national vaccination programme from the perspective of the Tanzanian government using data collected via surveys, workshops, and interviews with local stakeholders. Deterministic sensitivity analyses were performed to estimate the effect of alternative assumptions for coverage rates and delivery strategies and to assess the impact of a potential one-dose vaccination schedule. Results The total financial and economic costs were US$10,117,455 and US$45,683,204, respectively, at a financial cost of $5.17 per two-dose fully immunized girl (FIG), and an economic cost of $23.34 per FIG. Under the assumption of a one-dose vaccination schedule, costs per FIG would reduce to financial costs of $2.51 and economic costs of $12.18. Conclusions The overall cost of Tanzania’s HPV vaccination program was lower per vaccinee than previous demonstration projects in the region suggest. These data provide important baseline data for Tanzania’s HPV vaccination program to date and may serve as a guide for improving coverage going forward. The findings may also aid in the prioritization of funding for countries that have not yet added HPV vaccines to their routine immunizations. Key messages • If a single dose regimen were found to be as effective as a two-dose series, it would result in significant cost savings as well as an increase in the number of girls that could be reached. • School-based vaccinations resulted in the lowest price per fully immunized girl, but other settings are needed to achieve equitable high coverage of HPV vaccination in Tanzania.

Here, we report the NMR spectroscopic analysis of the group 8 transition metal methane σ-complexes [η

Comments on an article by K. J. Conover et al. (see record 2017-30398-007). Conover and colleagues developed and validated the self report Ableist Microaggressions Scale (AMS). Using factor analysis, the authors identified four subscales, including Helplessness, Minimization, Denial of Personhood, and Otherization. The psychometric properties of the AMS have been examined with adults with a range of disability types. The AMS consists of 20 items, and each item is scored on a 6- point Likert scale ranging from 0 (never) to 5 (very frequently). Total score ranges from 0 to 100, with higher scores reflecting greater experiences of microaggressions. Three positively worded items are reverse scored. The initial validation study included a sample size of 1,392 participants with various types of disabilities, an average age of 34, and a higher proportion of participants who identified as female relative to other sex/gender expressions, the majority of the sample identified as heterosexual and White. In this study, the AMS had good total-score internal consistency with a Cronbach's alpha of .91; three of the four subscales generally showed adequate as given their number of items: .83 for Helplessness, .90 for Denial of Personhood, and .84 for Otherization. However, the Minimization subscale displayed relatively weaker internal consistency with an a of .65. Additionally, the AMS showed adequate item-total correlations ranging from .21 to .77. Despite the high potential of the AMS to be used in research and clinical work, there are several limitations. The original validation study sample was comprised primarily of White heterosexual participants which may warrant caution in applications to racially/ethnically diverse groups and sexual minorities. Because individuals with mild-to-moderate disability may be less likely to participate in research, caution should also be exercised regarding generalizability to and use with more severe disability groups, including individuals with psychiatric disabilities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Vascular anomalies, both vascular tumors and vascular malformations, can occur in isolation or as part of syndromes including those which feature phenotypic overgrowth. To update what is known about vascular anomalies associated with overgrowth, PubMed was searched for "overgrowth syndromes and vascular anomalies or malformations." PubMed, OMIM, and the Rare Disease Database also were searched for specific diagnoses. We review individual overgrowth syndromes, provide a case-based approach to the clinical, radiographic, pathologic, and genetic basis for diagnosis, to complications of both the vascular anomalies and the overgrowth, and emphasize the need for a multidisciplinary approach to care.

Objectives To describe dosing practices for amantadine hydrochloride and related adverse effects among children and young adults with traumatic brain injury (TBI) admitted to pediatric inpatient rehabilitation units. Setting Eight pediatric acute inpatient rehabilitation units located throughout the United States comprising the Pediatric Brain Injury Consortium. Participants Two-hundred thirty-four children and young adults aged 2 months to 21 years with TBI. Design Retrospective data revie. Main outcome measures Demographic variables associated with the use of amantadine, amantadine dose, and reported adverse effects. Results Forty-nine patients (21%) aged 0.9 to 20 years received amantadine during inpatient rehabilitation. Forty-five percent of patients admitted to inpatient rehabilitation with a disorder of consciousness (DoC) were treated with amantadine, while 14% of children admitted with higher levels of functioning received amantadine. Children with DoC who were not treated with amantadine were younger than those with DoC who received amantadine (median 3.0 vs 11.6 years, P = .008). Recorded doses of amantadine ranged from 0.7 to 13.5 mg/kg/d; the highest total daily dose was 400 mg/d. Adverse effects were reported in 8 patients (16%); nausea/abdominal discomfort and agitation were most common, each reported in 3 patients. The highest reported dose without an adverse effect was 10.1 mg/kg/d. Conclusion During pediatric inpatient rehabilitation, amantadine was prescribed to children across a range of ages and injury severity and was most commonly prescribed to older children with DoC. Dosing varied widely, with weight-based dosing for younger/smaller children at both lower and higher doses than what had been previously reported. Prospective studies are needed to characterize the safety and tolerability of higher amantadine doses and optimize amantadine dosing parameters for children with TBI.