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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Introduction Cardiac resynchronisation therapy (CRT) in the form of His bundle CRT and left bundle area CRT can be more effective than the gold standard, biventricular pacing (BVP). In BVP scar burden is known to predict response whether this is true for these novel modalities is not known. Purpose The purpose of this study was to determine whether left ventricular scar burden assessed using cardiac MRI can be used to predict the electrical and acute haemodynamic response to two novel CRT modalities. Methods Patients with standard CRT indications were recruited. They underwent a pre-procedure cardiac MRI, with late gadolinium enhancement (LGE) to quantify scar. His bundle CRT (His CRT) and left bundle area CRT (LBA CRT) were attempted. The electrical response was measured using high precision non-invasive mapping ECGi (CardioInsight, Medtronic). The haemodynamic response was measured with a high precision protocol. We investigated the impact of scar and baseline electrical characteristic on ECGi and haemodynamic response. Results 26 patients were recruited (85% male, mean age 69 ± 10, with ischaemic cardiomyopathy in 35%). LGE was observed in 96% of cases and the mean (range 1-39%). We found a significant correlation between scar extent and the electrical response with both modalities. There was a significant correlation between a lower scar burden and better electrical response. For His CRT the reduction in left ventricular activation time was better with lower scar burden (R= 0.77, p < 0.01, Picture 1), for LBA CRT for reduction in left ventricular activation was also better with lower scar burden (R = 0.53, p = 0.05, Picture 2). With His CRT there was also a significant correlation between lower scar extent and better acute haemodynamic response ( R = 0.6, p = 0.002) but this was not observed with LBA CRT (R = 0.07, p = 0.77). Conclusion Left ventricular myocardial scar can be used to predict the electrical response to two different conduction system CRT modalities.

SARS-CoV-2 vaccines are useful tools to combat the Coronavirus Disease 2019 (COVID-19) pandemic, but vaccine reluctance threatens these vaccines’ effectiveness. To address COVID-19 vaccine reluctance and ensure equitable distribution, understanding the extent of and factors associated with vaccine acceptance and uptake is critical. We report the results of a large nationwide study in the US conducted December 2020-May 2021 of 36,711 users from COVID-19-focused smartphone-based app How We Feel on their willingness to receive a COVID-19 vaccine. We identified sociodemographic and behavioral factors that were associated with COVID-19 vaccine acceptance and uptake, and we found several vulnerable groups at increased risk of COVID-19 burden, morbidity, and mortality were more likely to be reluctant to accept a vaccine and had lower rates of vaccination. Our findings highlight specific populations in which targeted efforts to develop education and outreach programs are needed to overcome poor vaccine acceptance and improve equitable access, diversity, and inclusion in the national response to COVID-19.

ImportanceRetinopathy of prematurity (ROP) telemedicine screening programs have been found to be effective, but they rely on widefield digital fundus imaging (WDFI) cameras, which are expensive, making them less accessible in low- to middle-income countries. Cheaper, smartphone-based fundus imaging (SBFI) systems have been described, but these have a narrower field of view (FOV) and have not been tested in a real-world, operational telemedicine setting.ObjectiveTo assess the efficacy of SBFI systems compared with WDFI when used by technicians for ROP screening with both artificial intelligence (AI) and human graders.Design, Setting, and ParticipantsThis prospective cross-sectional comparison study took place as a single-center ROP teleophthalmology program in India from January 2021 to April 2022. Premature infants who met normal ROP screening criteria and enrolled in the teleophthalmology screening program were included. Those who had already been treated for ROP were excluded.ExposuresAll participants had WDFI images and from 1 of 2 SBFI devices, the Make-In-India (MII) Retcam or Keeler Monocular Indirect Ophthalmoscope (MIO) devices. Two masked readers evaluated zone, stage, plus, and vascular severity scores (VSS, from 1-9) in all images. Smartphone images were then stratified by patient into training (70%), validation (10%), and test (20%) data sets and used to train a ResNet18 deep learning architecture for binary classification of normal vs preplus or plus disease, which was then used for patient-level predictions of referral warranted (RW)– and treatment requiring (TR)–ROP.Main Outcome and MeasuresSensitivity and specificity of detection of RW-ROP, and TR-ROP by both human graders and an AI system and area under the receiver operating characteristic curve (AUC) of grader-assigned VSS. Sensitivity and specificity were compared between the 2 SBFI systems using Pearson χ2testing.ResultsA total of 156 infants (312 eyes; mean [SD] gestational age, 33.0 [3.0] weeks; 75 [48%] female) were included with paired examinations. Sensitivity and specificity were not found to be statistically different between the 2 SBFI systems. Human graders were effective with SBFI at detecting TR-ROP with a sensitivity of 100% and specificity of 83.49%. The AUCs with grader-assigned VSS only were 0.95 (95% CI, 0.91-0.99) and 0.96 (95% CI, 0.93-0.99) for RW-ROP and TR-ROP, respectively. For the AI system, the sensitivity of detecting TR-ROP sensitivity was 100% with specificity of 58.6%, and RW-ROP sensitivity was 80.0% with specificity of 59.3%.Conclusions and RelevanceIn this cross-sectional study, 2 different SBFI systems used by technicians in an ROP screening program were highly sensitive for TR-ROP. SBFI systems with AI may be a cost-effective method to improve the global capacity for ROP screening.

After more than three months of lava dome extrusion, La Soufrière (St. Vincent) transitioned to a series of explosive eruptions in April 2021. Here we present a time-series petrologic analysis of the phenocryst and microlite populations during the first ∼48 hours of explosivity to constrain ascent conditions and processes that drove changes in behavior. Primary eruptive products were crystal-rich (45-50 vol%) basaltic andesites with similar phenocryst phase assemblages and compositions. The change in eruptive style is consistent with overpresurization as a consequence of second boiling from anhydrous microlite crystallization. The microlites display variation between the explosive phases, with two populations: 1) “inherited” - normally zoned high-An plagioclase (>An 70 ) + olivine (Fo 62-79 ) + clinopyroxene + titanomagnetite, inferred to have crystallized at depths >15 km and high water pressures; 2) “juvenile” - unzoned plagioclase (An 45-65 ) + clinopyroxene + orthopyroxene + intermediate pyroxene (Wo 12-38 ) + titanomagnetite, inferred to have crystallized upon ascent due to decompression and degassing. Scoria from the first explosions featured extensive groundmass crystallization and a significant “inherited” microlite population. Later explosions had a more abundant “juvenile” microlite population and lower crystallinity, consistent with more rapid ascent from depth, initiated by decompression following initial blasts and destruction of the lava dome. Supplementary material at https://doi.org/10.6084/m9.figshare.c.6534864

MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here, it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/β-catenin signaling. Elevated mRNA cap methylation of Wnt signaling transcripts in response to MYC leads to augmented translational capacity, elevated protein levels, and enhanced Wnt signaling activity. Mechanistic evidence indicates that MYC promotes recruitment of RNA methyltransferase (RNMT) to Wnt signaling gene promoters by enhancing phosphorylation of serine 5 on the RNA polymerase II carboxy-terminal domain, mediated in part through an interaction between the TIP60 acetyltransferase complex and TFIIH.Implications: MYC enhances mRNA cap methylation above and beyond transcriptional induction. Mol Cancer Res; 15(2); 213–24. ©2016 AACR.

VAF concordance

Figure legends for Supplemental Figures 1 and 2

TFIIH, specifically CDK7, promotes mRNA cap methylation of canonical Wnt/beta-catenin signaling pathway transcripts.

Supplementary Data file including supplementary methods and clinical case vignettes.

S1. KLF5 binds the CCNE1 intronic region and contributes to CCNE1 expression in the J82 UBC cell line.

Reasons for not using recommended targeted therapy.

Description of supplemental data

S2. KLF5 promotes enhanced activity on the high risk versus low risk allele.

Patient sequencing data, by patient number and diagnosis.

Supplementary Figure S5: Segregation of potential causal variants in UTRN and PHACTR2 in families 30, 33 and 35. In all pedigrees, gray symbols represent non-affected individuals (coded as missing in the analysis) and black symbol represent affected individuals. The diagonal slash through the symbol represents a deceased individual and brackets around an individual's ID represents individuals who were sequenced. A) Family 30 pedigree with the first two letters underneath the individual ID represents the individual's genotype at rs186871831 (major allele = C, minor allele = T) and the second two letters underneath the individual ID represents the individual's genotype at rs966382235 (major allele = C, minor allele = T) B) Family 33 pedigree with the first two letters underneath the individual ID represents the individual's genotype at rs532363235 (major allele = A, minor allele = G) and the second two letters underneath the individual ID represents the individual's genotype at rs79313503 (major allele = G, minor allele = A) C) Family 33 pedigree with the first two letters underneath the individual ID represents the individual's genotype at rs191491353 (major allele = C, minor allele = A) and the second two letters underneath the individual ID represents the individual's genotype at rs553447284 (major allele = A, minor allele = T).

Regional LOD scores of haplotypes

Although lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we performed targeted sequencing on nine of our most strongly linked families. Two-point linkage analysis of the sequencing data revealed that the signal was heterogeneous and that different families likely had different risk variants. Three specific haplotypes were shared by some of the families: 6q25.3-26 in families 42 and 44, 6q25.2-25.3 in families 47 and 59, and 6q24.2-25.1 in families 30, 33, and 35. Region-based logarithm of the odds scores and expression data identified the likely candidate genes for each haplotype overlap: ARID1B at 6q25.3, MAP3K4 at 6q26, and UTRN (6q24.1) and PHACTR2 (6q24.2). Further annotation was used to zero in on potential risk variants in those genes. All four genes are good candidate genes for lung cancer risk, having been linked to either lung cancer specifically or other cancers. However, this is the first time any of these genes has been implicated in germline risk. Functional analysis of these four genes is planned for future work.Significance:This study identifies four genes associated with lung cancer risk, which could help guide future lung cancer prevention and treatment approaches.

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PDF file - 496K, Fig. S1-Immunoblot of Myc levels. Fig. S2-RT-PCR and Western blots of Ezh2 RNA and protein levels. Fig. S3-ChIP for Ring1b, H3K27 and Myc in different cell lines. Fig. S4-RT-PCR of select genes with siRNAs against Ezh2, PTEN or Miz1. Table S1-Myc activated genes that are unaltered by enhanced Ezh2 activity. Table S2-siRNA sequences used in experiments

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In this Perspective, we summarize the status of technological development for large-area and low-noise substrate-transferred GaAs/AlGaAs (AlGaAs) crystalline coatings for interferometric gravitational-wave (GW) detectors. These topics were originally presented as part of an AlGaAs Workshop held at American University, Washington, DC, from 15 August to 17 August 2022, bringing together members of the GW community from the laser interferometer gravitational-wave observatory (LIGO), Virgo, and KAGRA collaborations, along with scientists from the precision optical metrology community, and industry partners with extensive expertise in the manufacturing of said coatings. AlGaAs-based crystalline coatings present the possibility of GW observatories having significantly greater range than current systems employing ion-beam sputtered mirrors. Given the low thermal noise of AlGaAs at room temperature, GW detectors could realize these significant sensitivity gains while potentially avoiding cryogenic operation. However, the development of large-area AlGaAs coatings presents unique challenges. Herein, we describe recent research and development efforts relevant to crystalline coatings, covering characterization efforts on novel noise processes as well as optical metrology on large-area (similar to 10 cm diameter) mirrors. We further explore options to expand the maximum coating diameter to 20 cm and beyond, forging a path to produce low-noise mirrors amenable to future GW detector upgrades, while noting the unique requirements and prospective experimental testbeds for these semiconductor-based coatings.(c) 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http:// creativecommons.org/licenses/by/4.0/). https://doi.org/10.1063/5.0140663

Natural products discovered from bacteria provide critically needed therapeutic leads for drug discovery, and myxobacteria are an established source for metabolites with unique chemical scaffolds and biological activities. Myxobacterial genomes accommodate an exceptional number and variety of biosynthetic gene clusters (BGCs) which encode for features involved in specialized metabolism. Continued discovery and sequencing of novel myxobacteria from the environment provides BGCs for the genome mining pipeline. Herein, we describe the collection, sequencing, and genome mining of 20 myxobacteria isolated from rhizospheric soil samples collected in North America. Nine isolates where determined to be novel species of myxobacteria including representatives from the generaArchangium, Myxococcus, Nannocystis, Polyangium, Pyxidicoccus, Sorangium, andStigmatella. Growth profiles, biochemical assays, and descriptions are provided for all proposed novel species. We assess the BGC content of all isolates and observe differences between Myxococcia and Polyangiia clusters. Utilizing complete or near complete genome sequences we compare the chromosomal organization of BGCs of related myxobacteria from various genera and suggest spatial proximity of hybrid, modular clusters contributes to the metabolic adaptability of myxobacteria.

Background The efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension. Methods We systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed. Results 6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation. Conclusions The totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.

We present a detailed characterization and comparative study of a membrane external-cavity surface-emitting laser (MECSEL) operating in the λ = 1125-1190 nm wavelength range under in-well pumping (at 1070 nm) and barrier-pumping (at 808 nm). The slope efficiency of the laser is significantly improved from 21% with barrier-pumping to 39% when pumping only the quantum wells at 1070 nm at a heat-sink temperature of 10 °C. To address the low pump absorbance with in-well pumping, we design and implement a low-aberration multi-pass pumping scheme. An optical output power of 28.5 W and slope efficiency of ∼28% is achieved with 8 circulating passes. This represents the highest output power demonstrated in any MECSEL, as well as the highest output power in-well pumped vertical external-cavity surface-emitting laser (VECSEL). It is noted that our reported output power is only limited by the available laser input power and no thermal roll-over is observed.

To determine the impact of emergent transition from in-person to remote learning on student performance within real-time objective structured clinical examinations (OSCEs).A university mandate, due to severe SARS-CoV-2, was issued requiring didactic courses to transition to remote learning in spring 2020. The third-year internal medicine elective had six remaining weekly OSCEs, accounting for 55% of course grades. Full credit was awarded for the first OSCE as students familiarized themselves with the new virtual format. The primary outcome was the overall average OSCE performance for the course's remaining five virtual simulations compared to the traditional in-person offering in 2019. Secondary outcomes included individual OSCE performance, OSCE performance with inclusion of the first OSCE, and overall course grades.There were no statistically significant differences in overall average OSCE performance between 2019 and 2020 cohorts for the five simulations (82.7% vs. 86.8%, P = .20). Secondary outcomes showed statistically significant differences favoring performance in the 2020 cohort for infectious diseases (78.3% vs. 89.4%, P .001) and anticoagulation (74.4% vs. 90%, P = .002), while cardiology favored the 2019 cohort (91.1% vs. 82.8%, P = .03). There was no statistically significant difference in performance on the cumulative I (86.1% vs. 82.2%, P = .41) or cumulative II (83.3% vs. 89.4%, P = .29) simulations or in final overall course grades (86.6% vs. 90.2%, P = .06).An emergent transition to remote learning may not negatively impact student performance on real-time OSCE activities.

Globally, carbapenemase-producing Enterobacterales (CPE) cause life-threatening, hospital-acquired infections in people, and have been reported recently among veterinary patients. Organisms that produce a Klebsiella pneumoniae carbapenemase (KPC) are one of the most common CPE isolated from people but have been reported only rarely in animals. We characterized 2 KPC-producing Enterobacterales isolated from companion animal rectal swabs during the response to an outbreak caused by a strain of blaNDM-5 Escherichia coli. Both isolates were characterized by whole-genome sequencing (WGS) and analysis. The first isolate (case A) was from an immunosuppressed 6-y-old Yorkshire Terrier and was identified as E. coli (ST372) with a blaKPC-18 gene and an IncFII plasmid. The second isolate (case B) was from a 3-y-old Labrador Retriever with acute diarrhea and was identified as Citrobacter koseri with a blaKPC-2 gene, multiple plasmids (ColRNAI, pKPC-CAV1193), and a putative enterotoxin gene ( senB). Further research is needed to determine what role animals might play in the epidemiology of CPE in communities. It is imperative that all CPE isolated from companion animals be fully characterized by WGS and the associated case examined. All veterinary isolates should be sequenced and shared for surveillance, monitoring, and investigation purposes.

IntroductionLeft bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. A proposed solution is to advance RV activation through anodal capture, but there is uncertainty regarding the mechanism by which early RV activation is achieved (capture of right bundle or RV myocardial capture) and it is not known whether this produces hemodynamic benefit.MethodsWe recruited patients with LBBP leads in whom anodal capture eliminated the terminal R wave in lead V1.Ventricular activation pattern, timing and high precision acute hemodynamic response were studied during LBBP with and without anodal capture.ResultsWe recruited 21 patients, mean age 67 years, 14 were males. We measured ECG timings and hemodynamics in all patients and in 15 we also performed non-invasive mapping. Ventricular epicardial propagation maps demonstrated that right ventricular septal myocardial capture, rather than right bundle capture, was the mechanism for earlier RV activation. With anodal capture, QRS duration was shorter (116 ± 12ms versus 129 ± 14ms, p < 0.01), and total ventricular activation time was shorter (83 ± 18ms versus 90 ± 15ms, p = 0.01). This required higher outputs (3.6 ± 1.9V versus 0.6 ± 0.2V, p ConclusionLeft bundle pacing with anodal capture advances right ventricular activation as a result of stimulation of the RV septal myocardium. However, this requires higher outputs and did not improve acute hemodynamics. Aiming for anodal capture may therefore not be necessary.

BACKGROUND: Team-based learning (TBL) encourages learners to think critically to solve problems they will face in practice. Pharmacokinetic dosing and monitoring are complex skills requiring the application of learned knowledge. The study sought to assess the impact of a TBL, vancomycin dosing activity in a Pharmaceutical Skills IV course measured with exam question performance during the second professional year. METHODS: This retrospective, descriptive study relates a TBL activity, assigned to 85 students, which included an individual student pre-preparation quiz, assigned readings, in-class individual and team-based readiness assessments, small group application of a vancomycin patient case, and group discussion/feedback on clinical decisions with supportive reasoning. The class year before and class year of the TBL implementation were compared using the total percentage of points possible earned by the class years, by topic. To minimize potential confounding, the primary outcome was the change in topic performance by the rank difficulty (e.g., the largest possible benefit being the hardest topic becoming the easiest with no other variation in topic rank difficulty). RESULTS: In the year of implementation, the mean individual readiness assurance test (IRAT) performance was 5.5 ± 1.88 (10 points possible, 55%). The mean team readiness assurance test (TRAT) performance was 10 of 10 points possible (100%). The class exam item performance in the year before (n = 101) and year of (n = 84) TBL implementation showed a general decline in exam scores. However, the vancomycin topic difficultly went from fifth easiest, to second easiest, with less than 1% change in raw score. CONCLUSIONS: Implementation of a pharmacokinetic TBL activity appeared to moderately support the students’ vancomycin learning. Additional studies are warranted on APPE readiness and performance.

Thermal noise in high-reflectivity mirror coatings is a limiting factor in ground-based gravitational wave detectors. Reducing this coating thermal noise improves the sensitivity of detectors and enriches the scientific outcome of observing runs. Crystalline gallium arsenide and aluminum-alloyed gallium arsenide (referred to as AlGaAs) coatings are promising coating candidates for future upgrades of gravitational wave detectors because of their low coating thermal noise. However, AlGaAs-based crystalline coatings may be susceptible to an electro-optic noise induced by fluctuations in an electric field. We investigated the electro-optic effect in an AlGaAs coating by using a Fabry-Perot cavity, and concluded that the noise level is well below the sensitivity of current and planned gravitational-wave detectors.

Children, adolescents, and young adults (CAYA) with relapsed/refractory classical Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with relapsed/refractory cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score >3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary endpoint was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued); 11 of whom received intensification, 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV, and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year PFS rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with relapsed/refractory cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. ClinicalTrials.gov: NCT02927769.

PURPOSEWe report the results from a Foundation for the National Institutes of Health Biomarkers Consortium project to address the absence of well-validated quality control materials (QCMs) for circulating tumor DNA (ctDNA) testing. This absence is considered a cause of variance and inconsistencies in translating ctDNA results into clinical actions.METHODSIn this phase I study, QCMs with 14 clinically relevant mutations representing single nucleotide variants, insertions or deletions (indels), translocations, and copy number variants were sourced from three commercial manufacturers with variant allele frequencies (VAFs) of 5%, 2.5%, 1%, 0.1%, and 0%. Four laboratories tested samples in quadruplicate using two allele-specific droplet digital polymerase chain reaction and three (amplicon and hybrid capture) next-generation sequencing (NGS) panels.RESULTSThe two droplet digital polymerase chain reaction assays reported VAF values very close to the manufacturers’ claimed concentrations for all QCMs. NGS assays reported most single nucleotide variants and indels, but not translocations, close to the expected VAF values. Notably, two NGS assays reported lower VAF than expected for all translocations in all QCM mixtures, possibly related to technical challenges detecting these variants. The ability to call ERBB2 copy number amplifications varied across assays. All three QCMs provided valuable insight into assay precision. Each assay across all variant types demonstrated dropouts at 0.1%, suggesting that the QCM can serve for testing of an assay’s limit of detection with confidence claims for specific variants.CONCLUSIONThese results support the utility of the QCM in testing ctDNA assay analytical performance. However, unique designs and manufacturing methods for the QCM, and variations in a laboratory’s testing configuration, may require testing of multiple QCMs to find the best reagents for accurate result interpretation.

Objective To study the outcomes of a novel modified pulmonary artery banding (mPAB) technique used for staged repair of a subset of patients with complex transposition physiology. Methods A total of 13 patients who underwent mPAB during their staged repair (biventricular repair [BVR], n = 6) or palliation (1-1/2 repair, n = 1; univentricular repair [UVR], n = 6) from 2004 to 2020 were studied retrospectively. A restrictive interposition graft was used to reconstruct the main PA between the pulmonary root and the distal pulmonary confluence, functioning as a mPAB. Twelve of the 13 patients (92.3%) underwent a concurrent arterial switch operation (ASO), of which 6 were palliative ASOs for 1-1/2 repair (n = 1) or UVR (n = 5). Patient weight and cardiac anatomy determined the size of interposition graft. Results The disease spectrum included dextro transposition of the great arteries (d-TGA) with multiple ventricular septal defects (VSDs) (n = 4), Taussig–Bing anomaly (n = 3), d-TGA with VSD and hypoplastic right ventricle (RV) (n = 3), double-inlet left ventricle with l-TGA (n = 2), and congenitally corrected TGA with double-outlet RV (n = 1). The Lecompte procedure was performed in 10 patients. Predischarge echocardiography revealed a band gradient of 61 mm Hg (interquartile range [IQR], 40-90 mm Hg) for BVR/1-1/2 ventricular repair (n = 7) and 49 mm Hg (IQR, 37-61 mm Hg) for UVR (n = 6). Survival was 100% at a median follow-up of 3.7 years (IQR, 2.6-4.0 years). Conclusions The mPAB technique is effective and reproducible for staged BVR or UVR for patients with TGA. It effectively regulates pulmonary blood flow, may reduce neopulmonary root distortion, and eliminates complications associated with band migration in standard PAB., Graphical abstract

Introduction Continuing education (CE) standards by the Accreditation Council for Pharmacy Education emphasize that educational methodologies should contribute to the development of participants' critical thinking and problem-solving skills. Employment of serious gaming can meet this expectation through motivation, timely feedback, and challenging all performance levels. Current literature is lacking regarding use of game-based learning, such as “escape rooms” in pharmacy CE programming. Methods This pilot study enrolled participants at a two-hour medication error CE presentation. Study investigators utilized the first hour for lecture and the second hour for application through an “escape room” activity. During this activity, participants used critical thinking and teamwork to unlock puzzles for root cause analysis (RCA) creation in a provided timeframe. An optional, online anonymous survey was emailed to attendees. Responses were rated on a five-point Likert scale; descriptive statistics were represented by percent distributions. Results A total of 40 pharmacists and seven technicians responded to the perception survey. Most respondents felt this activity emphasized critical thinking (87%) and was appropriate for the topic of medication errors (83%). The majority (63%) agreed this activity helped them to better understand a RCA, 48% felt the group sizes were appropriate, and 76% felt instructions for the activity were clear. Over 75% would like to see this type of activity utilized in another CE programs. Conclusions This activity was well received by participants and may emphasize critical thinking and understanding of topics presented. Further studies assessing pre−/post-program knowledge are needed to ensure adequate retention of information.