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OBJECTIVE: To evaluate the role of psychosocial well-being on perioperative pain and opioid use among patients with cleft lip and palate (CLP) undergoing alveolar bone grafting (ABG). DESIGN: Retrospective review. SETTING: Tertiary level craniofacial clinic. PARTICIPANTS: 34 patients with CLP (median age: 11.7 years), including 25 (73.5%) unilateral CLP and 9 (26.5%) bilateral CLP, who underwent ABG from 2015 to 2022. INTERVENTIONS: ABG using iliac crest bone graft. Patients were prospectively administered four patient-reported psychosocial instruments from the Patient-Reported Outcomes Measurement Information System. MAIN OUTCOME MEASURES: Perioperative opioid use in morphine equivalent dosage/kilogram, patient-reported pain scores, and length of hospital stay after ABG. RESULTS: Patient-reported anxiety (r = 0.41, p = 0.02) and depressive symptoms (r = 0.35, p = 0.04) correlated to higher perioperative opioid usage. Multivariable regression models including psychosocial scores, total acetaminophen usage, length of surgery, and other simultaneous surgeries were developed for total opioid usage, patient-reported pain, and length of hospital stay. Patient-reported anxiety was independently predictive of higher perioperative opioid use (β=0.36, p = 0.01) and higher pain scores (β=0.39, p = 0.02), but not length of hospital stay. CONCLUSIONS: We identified an association for patient-reported anxiety and perioperative opioid use and pain in a CLP cohort undergoing ABG. Future considerations in preoperative patient and family consultation may be indicated in patients self-reporting higher anxiety in an effort to minimize perioperative opioid usage.

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs1-3 and revealed how quickly viral escape can curtail effective options4,5. When the SARS-CoV-2 Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab4-6. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination4 and is challenging to replace with existing approaches. Rapidly modifying such high-value antibodies to restore efficacy against emerging variants is a compelling mitigation strategy. We sought to redesign and renew the efficacy of COV2-2130 against Omicron BA.1 and BA.1.1 strains while maintaining efficacy against the dominant Delta variant. Here we show that our computationally redesigned antibody, 2130-1-0114-112, achieves this objective, simultaneously increases neutralization potency against Delta and subsequent variants of concern, and provides protection in vivo against the strains tested: WA1/2020, BA.1.1 and BA.5. Deep mutational scanning of tens of thousands of pseudovirus variants reveals that 2130-1-0114-112 improves broad potency without increasing escape liabilities. Our results suggest that computational approaches can optimize an antibody to target multiple escape variants, while simultaneously enriching potency. Our computational approach does not require experimental iterations or pre-existing binding data, thus enabling rapid response strategies to address escape variants or lessen escape vulnerabilities.

Topological phases in laterally confined low-dimensional nanographenes have emerged as versatile design tools that can imbue otherwise unremarkable materials with exotic band structures ranging from topological semiconductors and quantum dots to intrinsically metallic bands. The periodic boundary conditions that define the topology of a given lattice have thus far prevented the translation of this technology to the quasi-zero-dimensional (0D) domain of small molecular structures. Here, we describe the synthesis of a polycyclic aromatic hydrocarbon (PAH) featuring two localized zero modes (ZMs) formed by the topological junction interface between a trivial and nontrivial phase within a single molecule. First-principles density functional theory calculations predict a strong hybridization between adjacent ZMs that gives rise to an exceptionally small HOMO-LUMO gap. Scanning tunneling microscopy and spectroscopy corroborate the molecular structure of 9/7/9-double quantum dots and reveal an experimental quasiparticle gap of 0.16 eV, corresponding to a carbon-based small molecule long-wavelength infrared (LWIR) absorber.

To accelerate medical breakthroughs, the All of Us Research Program aims to collect data from over one million participants. This report outlines processes used to construct the All of Us Social Determinants of Health (SDOH) survey and presents the psychometric characteristics of SDOH survey measures in All of Us. A consensus process was used to select SDOH measures, prioritizing concepts validated in diverse populations and other national cohort surveys. Survey item non-response was calculated, and Cronbachs alpha was used to analyze psychometric properties of scales. Multivariable logistic regression models were used to examine associations between demographic categories and item non-response. Twenty-nine percent (N = 117,783) of eligible All of Us participants submitted SDOH survey data for these analyses. Most scales had less than 5% incalculable scores due to item non-response. Patterns of item non-response were seen by racial identity, educational attainment, income level, survey language, and age. Internal consistency reliability was greater than 0.80 for almost all scales and most demographic groups. The SDOH survey demonstrated good to excellent reliability across several measures and within multiple populations underrepresented in biomedical research. Bias due to survey non-response and item non-response will be monitored and addressed as the survey is fielded more completely.

In this articlewe provide some lists of real numberswhich can be realized as the spectra of nonnegative diagonalizable matrices but which are not the spectra of nonnegative symmetric matrices. In particular, we examine the classical list σ = (3 + t, 3 − t, −2, −2, −2) with t ≥ 0, and show that 0 is realizable by a nonnegative diagonalizable matrix only for t ≥ 1. We also provide examples of lists which are realizable as the spectra of nonnegative matrices, but not as the spectra of nonnegative diagonalizable matrices by examining the Jordan Normal Form

This article makes a case for SoTL practitioners to engage in what we term a pedagogy of slow. Here, "slow" connotes with waiting and patience. It takes time to learn and acquire the skills that a SoTL scholar needs. "Doing SoTL" we therefore argue, requires a pedagogy that takes time and sees time as an ally instead of as an opponent. In what the university has become, there seems little room for a pedagogy of slow that both offers and allows for time. In this article we present a case for considering engagement with the visual arts as part of a pedagogy of slow and the development of SoTL. By making the familiar strange, we acknowledge the implications of visual thinking strategies for social engagement by highlighting teaching and learning as relational. Working with colleagues in the context of continuing professional development, we collected data via focus groups and written reflections within physical and virtual gallery spaces to glean insight into participant experiences of slow looking as the antithesis to fast-paced and pressurised environments. We highlight how learning to become a SoTL scholar is an iterative process that requires time and generates what we term "productive friction." This is the iterative process which creates dislocation and uncertainty within participants, but which also has the capacity to nudge towards a transformation of the professional self.

AbstractSickle cell disease (SCD) is a genetic disorder affecting 100 000 people with an estimated annual medical cost of $3 billion in the United States; however, the economic impact on patients is not well described. We aimed to examine the indirect economic burden and test the hypothesis that socioeconomic status and greater social vulnerability risks are associated with increased absenteeism and employment loss. We surveyed adults and caregivers of children with SCD at 5 US centers from 2014 to 2021. Logistic regression models were used to examine the associations of employment loss and missed days of work with demographics and social determinants. Indirect costs were estimated by multiplying the self-reported missed days of work and job loss by 2022 average wages by the state of the participating institution. Of the 244 participants, 10.3% reported employment loss in the last 5 years, and 17.5% reported missing 10 or more days of work. Adults had 3 times more employment loss compared with caregivers of children with SCD (OR, 3.18; 95% CI, 1.12-9.01) but fewer missed days of work (OR, 0.24; 95% CI, 0.11-0.0.51). Participants who did not live with a partner reported increased employment loss (OR, 4.70; 95% CI, 1.04-21.17) and more missed days of work (OR, 4.58; 95% CI, 1.04-20.15). The estimated annual indirect economic burden was $2 266 873 ($9290 per participant). Adults with SCD and caregivers of children with SCD commonly report employment loss and missed days of work as important risk factors. The high indirect economic burden suggests that future economic evaluations of SCD should include SCD-related indirect economic burden.

Exercising direct control over the unusual electronic structures arising from quantum confinement effects in graphene nanoribbons (GNRs) is intimately linked to geometric boundary conditions imposed by the structure of the ribbon. Besides composition and position of substitutional dopant atoms, the symmetry of the unit cell, width, length, and termination of a GNR govern its electronic structure. Here, we present a rational design that integrates each of these interdependent variables within a modular bottom-up synthesis. Our hybrid chemical approach relies on a catalyst-transfer polymerization that establishes excellent control over length, width, and end groups. Complemented by a surface-assisted cyclodehydrogenation step, uniquely enabled by matrix-assisted direct (MAD) transfer protocols, geometry and functional handles encoded in a polymer template are faithfully mapped onto the structure of the corresponding GNR. Bond-resolved scanning tunneling microscopy (BRSTM) and spectroscopy (STS) validate the robust correlation between polymer template design and GNR electronic structure.

BACKGROUND: We designed a survey to evaluate preferences of facial appearance in transgender male (TM), transgender female (TF) and gender nonbinary patients to better inform goals of facial gender affirming surgery (FGAS) in gender nonbinary patients. METHODS: TM/TF and nonbinary patients > 18 years old were identified via retrospective chart review and distributed an anonymized survey via email from October 3 to December 31, 2022. To assess facial preferences, AI-generated and open-source portraits were edited to create five image sets with a range of features from masculine to feminine for the forehead, mandible/chin and hairline. Data were analyzed using Fishers exact tests and ANOVA in R-Studio. RESULTS: Survey response rate was 32% (180 patients identified via chart review, 58 respondents; TM = 5, TF = 39, nonbinary = 14). TM and TF patients as well as TF and nonbinary patients had significantly different preferences for all regions (p  0.05; all series). TF patients consistently selected 4s with neutral or more feminine features. TM and nonbinary patients, however, demonstrated no consistent preference for either male or female features but rather a range of responses spanning extremes of both masculine and feminine options. When stratified by sex assigned at birth, nonbinary patients consistently identified preferences opposite to their assigned gender. CONCLUSION: Gender nonbinary and TM patients appear to have uniquely individual preferences regarding facial appearance that do not fit into classically masculine or feminine patterns/phenotypes. As a result, we recommend individualized preoperative planning for FGAS to achieve the optimal result in these patient populations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

AIM: The 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. METHODS: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation and the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

UNLABELLED: On 15 January 2022, Hunga volcano erupted, creating an extensive and high-reaching umbrella cloud over the open ocean, hindering traditional isopach mapping and fallout volume estimation. In MODIS satellite imagery, ocean surface water was discolored around Hunga following the eruption, which we attribute to ash fallout from the umbrella cloud. By relating intensity of ocean discoloration to fall deposit thicknesses in the Kingdom of Tonga, we develop a methodology for estimating airfall volume over the open ocean. Ash thickness measurements from 41 locations are used to fit a linear relationship between ash thickness and ocean reflectance. This produces a minimum airfall volume estimate of 1.8-0.4+0.3 km3. The whole eruption produced > 6.3 km3 of uncompacted pyroclastic material on the seafloor and a caldera volume change of 6 km3 DRE. Our fall estimates are consistent with the interpretation that most of the seafloor deposits were emplaced by gravity currents rather than fall deposits. Our proposed method does not account for the largest grain sizes, so is thus a minimum estimate. However, this new ocean-discoloration method provides an airfall volume estimate consistent with other independent measures of the plume and is thus effective for rapidly estimating fallout volumes in future volcanic eruptions over oceans. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00445-024-01744-6.

BACKGROUND The Miller’s Review of Orthopaedics (MRO) and the AAOS Comprehensive Orthopaedic Review (COR) are two commonly used review books for the Orthopaedic In-Training Examination (OITE). However, both resources are quite extensive in terms of book length. The authors recently published a concise OITE review handbook titled High-Yield Orthopaedics (HYO). This study aimed to validate HYO by determining the prevalence of 2018 OITE answers found in the handbook.METHODS The 2018 OITE questions were categorized into one of three question types by the first author. Taxonomy 1 (T1) questions tested recall or recognition; taxonomy 2 (T2) questions tested interpretation; and taxonomy 3 (T3) questions tested problem-solving. Two authors (HVL and PKC) then independently reviewed HYO to determine if answers to the 2018 OITE questions were available in the handbook. Interobserver reliability was assessed via percent agreement and Cohen’s kappa (κ) coefficient. Discrepancies were resolved after joint review.RESULTS Of the 270 OITE questions available for review, 97 (35.9%) were classified as T1 questions, 85 (31.5%) as T2 questions, and 88 (32.6%) as T3 questions. The answers to 198 OITE questions (73.3%) were detected in HYO—58 answers to T1 questions (59.8%), 63 answers to T2 questions (74.1%), and 77 answers to T3 questions (87.5%). The concordance between the two reviewers was 258 out of 270 questions (95.6%) with κ coefficient of 0.88.CONCLUSION Compared to MRO and COR, High-Yield Orthopaedics is a more concise resource that still comprehensively reviews all 11 knowledge domains tested on the OITE. Answers to 198 of the 270 questions (73.3%) on the 2018 OITE were found in the handbook. HYO is a valid and high-yield review material for OITE preparation.LEVEL OF EVIDENCE Level V Expert Opinion

Abstract Background This study examined the association between menopausal symptoms and job satisfaction, and ascertained whether three psychosomatic factors (e.g., anxiety, depression, and sleep quality) interact with menopausal symptoms on job satisfaction. Methods A cross-sectional design with sensitivity analysis was adopted. The participants of the study were clinical health workers in England. Data from 154 health workers were analyzed with the hierarchical linear regression (HLR) analysis. Results There was a negative association between menopausal symptoms and job satisfaction (β = −0.38; t = −4.81, p 0.05) but was strengthened by anxiety (β = −0.22; t = −2.28; p

Background: The 2015 American Thyroid Association (ATA) guidelines added thyroid lobectomy (TL) as the appropriate treatment for low-risk differentiated thyroid cancer (DTC). We aimed to investigate the population-level factors that influence the utilization of TL. Methods: The Surveillance, Epidemiology and End Results (SEER) database was queried for all DTC patients fitting low-risk criteria as defined by the ATA. Trends in total thyroidectomy (TT) and TL were identified using a Cochrane– Armitage test. Multivariable logistic regression identified patient and socioeconomic characteristics associated with TL, and difference-in-difference analysis was used to control for secular trends over time. Results: A total of 43,526 patients with low-risk DTC were identified in the SEER database; 39,411 pre-2015 and 4115 post-2015. After 2015, TT continued to outnumber TL (76.2% vs 23.8%), although the rate of TL increased significantly (11.6% to 23.8%, P < 0.001). However, difference-in-difference analysis found that age > 55 (OR 1.11, 95% CI 1.01–1.19, P < 0.001) and rurality (OR 1.16, 95% CI 1.05–1.28, P < 0.001) were independently associated with TT. TL was associated with T1 disease (OR 1.11, 95% CI 1.04–1.19, P = 0.001). Conclusion: Although the 2015 ATA guideline update led to an increase in TL for low-risk DTC, most patients still underwent TT. Age and neighborhood significantly impact the odds of receiving guideline-appropriate TL for low-risk DTC, especially for T2 disease.

Abstract Background Atopic dermatitis (AD) is associated with patient burden, but few studies describe the anatomic distribution of the disease or the impact of number of lesion locations. Objectives To describe lesion locations and assess the relationship between the number of lesion locations (disease extent) and disease burden in patients with AD. Methods This cross‐sectional study included adults with dermatologist‐ or dermatology practitioner‐diagnosed AD enroled in the CorEvitas AD Registry (2020–2021) who initiated systemic therapy within 12 months prior to or at enrolment or had moderate‐to‐severe AD (vIGA‐AD® ≥3 and EASI ≥12) at enrolment. Thirteen areas of lesion involvement were assessed using a body map, and numbers of lesion locations were categorised as: 0, 1, 2–3, 4–6 and ≥7. Demographics, disease characteristics, PROs by number of lesion locations were descriptively compared using effect sizes (ES). The ES thresholds for small, medium, and large differences, respectively, were 0.10, 0.30, and 0.50 for phi (categorical outcomes) and 0.10, 0.25 and 0.40 for Cohen's f (continuous outcomes). Results Among 1211 patients, lesion involvement was most frequent on the arms (69.5%) and lower limbs (61.7%). A total of 10.6%, 9.3%, 20.1%, 26.3% and 33.8% of patients had 0, 1, 2–3, 4–6 and ≥7 lesion locations, respectively. Current use of systemic (≥81.2%) and topical ( ≥74.7%) therapies was common, irrespective of lesion location. Disease severity increased with number of lesion locations: mean total BSA (ES = 1.17), EASI (ES = 1.11), and SCORAD (ES = 1.21). vIGA‐AD ≥3 was observed in 28.3%, 45.3%, 78.0%, and 93.9% of patients with 1, 2–3, 4–6 and ≥7 locations, respectively (ES = 0.63). Greater number of lesion locations was associated with worse PROs: mean POEM (ES = 0.57), sleep loss (ES = 0.41), peak pruritus (ES = 0.50), DLQI (ES = 0.40), and ADCT (ES = 0.53). Uncontrolled AD (ADCT ≥7) was observed in 48.2%, 52.9%, 70.4%, 81.6% of patients with 1, 2–3, 4–6 and ≥7 locations, respectively (ES = 0.42). Conclusions AD lesions were reported for each body area assessed. Greater number of lesion locations was associated with increased disease severity, poor disease control, and decreased quality of life. Patients experienced substantial disease burden regardless of number of lesion locations involved.

Abstract Background Prokaryotic microbes have impacted marine biogeochemical cycles for billions of years. Viruses also impact these cycles, through lysis, horizontal gene transfer, and encoding and expressing genes that contribute to metabolic reprogramming of prokaryotic cells. While this impact is difficult to quantify in nature, we hypothesized that it can be examined by surveying virus-encoded auxiliary metabolic genes (AMGs) and assessing their ecological context. Results We systematically developed a global ocean AMG catalog by integrating previously described and newly identified AMGs and then placed this catalog into ecological and metabolic contexts relevant to ocean biogeochemistry. From 7.6 terabases of Tara Oceans paired prokaryote- and virus-enriched metagenomic sequence data, we increased known ocean virus populations to 579,904 (up 16%). From these virus populations, we then conservatively identified 86,913 AMGs that grouped into 22,779 sequence-based gene clusters, 7248 (~ 32%) of which were not previously reported. Using our catalog and modeled data from mock communities, we estimate that ~ 19% of ocean virus populations carry at least one AMG. To understand AMGs in their metabolic context, we identified 340 metabolic pathways encoded by ocean microbes and showed that AMGs map to 128 of them. Furthermore, we identified metabolic “hot spots” targeted by virus AMGs, including nine pathways where most steps (≥ 0.75) were AMG-targeted (involved in carbohydrate, amino acid, fatty acid, and nucleotide metabolism), as well as other pathways where virus-encoded AMGs outnumbered cellular homologs (involved in lipid A phosphates, phosphatidylethanolamine, creatine biosynthesis, phosphoribosylamine-glycine ligase, and carbamoyl-phosphate synthase pathways). Conclusions Together, this systematically curated, global ocean AMG catalog and analyses provide a valuable resource and foundational observations to understand the role of viruses in modulating global ocean metabolisms and their biogeochemical implications. Video Abstract

Methyl‐coenzyme M reductase (MCR) is a multi‐subunit (α2β2γ2) enzyme responsible for methane formation via its unique F430 cofactor. The genes responsible for producing MCR (mcrA, mcrB and mcrG) are typically colocated with two other highly conserved genes mcrC and mcrD. We present here the high‐resolution crystal structure for McrD from a human gut methanogen Methanomassiliicoccus luminyensis strain B10. The structure reveals that McrD comprises a ferredoxin‐like domain assembled into an α + β barrel‐like dimer with conformational flexibility exhibited by a functional loop. The description of the M. luminyensis McrD crystal structure contributes to our understanding of this key conserved methanogen protein typically responsible for promoting MCR activity and the production of methane, a greenhouse gas.

Abstract Structural information deficits about aging bridges have led to several avoidable catastrophes in recent years. Data-driven methods for bridge vibration monitoring enable frequent, accurate structural assessments; however, the high costs of widespread deployments of these systems make important condition information a luxury for bridge owners. Smartphone-based monitoring is inexpensive and has produced structural information, i.e., modal frequencies, in crowdsensing applications. Even so, current methods cannot extract spatial vibration characteristics with uncontrolled datasets that are needed for damage identification. Here we present an extensive real-world study with crowdsourced smartphone-vehicle trips within motor vehicles in which we estimate absolute value mode shapes and simulate damage detection capabilities. Our method analyzes over 800 trips across four road bridges with main spans ranging from 30 to 1300 m in length, representing about one-quarter of bridges in the United States. We demonstrate a bridge health monitoring platform compatible with ride-sourcing data streams that check conditions daily. The result has the potential to commodify data-driven structural assessments globally.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.