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Background: Self-regulation is crucial for children's learning and development. Several studies have explored children's inter-individual differences in self-regulation, but little is known about sources of intra-individual variation. Aims: This study addressed the variability of children's self-regulation across typical classroom situations and how this might be associated with children's executive functions (EFs). Sample: The study included 148 children (54.7% girls; M[subscript age] = 56.73 months). Methods: Self-regulation was assessed with an observational measure in teacher-led and child-led activities within naturalistic classroom settings. Children's EFs were assessed with direct assessments at the start and end of the school year. Results: Linear mixed-effect models showed that children demonstrated higher levels of self-regulation in child-led in comparison with teacher-led activities. Children with higher levels of EFs at the start of the school year showed less variation across teacher-led and child-led activities in comparison with children with lower levels of EFs. Regarding other aspects of the classroom context, neither the group size in which the activity took place nor which school subject it was focused on were associated with children's self-regulation. However, in teacher-led activities the type of interaction involved in the activity and the type of task influenced children's self-regulation. Conclusion: These results suggest that children who start school with higher levels of EFs are more able to adapt to different situations, highlighting the importance of fostering these skills in early childhood. In turn, children with lower levels of EFs may need additional support from teachers to remain self-regulated across different contexts.

Abstract Rare genetic diseases are typically studied in referral populations, resulting in underdiagnosis and biased assessment of penetrance and phenotype. To address this, we develop a generalizable method of genotype inference based on distant relatedness and deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population. We identify 9 LQT5 families referred to a single specialty clinic, each carrying p.Asp76Asn, the most common LQT5 variant. We uncover recent common ancestry and a single shared haplotype among probands. Application to a non-referral population of 69,819 BioVU biobank subjects identifies 22 additional subjects sharing this haplotype, which we confirm to carry p.Asp76Asn. Referral and non-referral carriers have prolonged QT interval corrected for heart rate (QTc) compared to controls, and, among carriers, the QTc polygenic score is independently associated with QTc prolongation. Thus, our innovative analysis of shared chromosomal segments identifies undiagnosed cases of genetic disease and refines the understanding of LQT5 penetrance and phenotype.

Adenoviruses (Ads) have demonstrated significant success as replication-deficient (RD) viral vectored vaccines, as well as broad potential across gene therapy and cancer therapy. Ad vectors transduce human cells via direct interactions between the viral fiber knob and cell surface receptors, with secondary cellular integrin interactions. Ad receptor usage is diverse across the extensive phylogeny. Commonly studied human Ad serotype 5 (Ad5), and chimpanzee Ad-derived vector “ChAdOx1” in licensed ChAdOx1 nCoV-19 vaccine, both form primary interactions with the coxsackie and adenovirus receptor (CAR), which is expressed on human epithelial cells and erythrocytes. CAR usage is suboptimal for targeted gene delivery to cells with low/negative CAR expression, including human dendritic cells (DCs) and vascular smooth muscle cells (VSMCs). We evaluated the performance of an RD Ad5 vector pseudotyped with the fiber knob of human Ad serotype 49, termed Ad5/49K vector. Ad5/49K demonstrated superior transduction of murine and human DCs over Ad5, which translated into significantly increased T cell immunogenicity when evaluated in a mouse cancer vaccine model using 5T4 tumor-associated antigen. Additionally, Ad5/49K exhibited enhanced transduction of primary human VSMCs. These data highlight the potential of Ad5/49K vector for both vascular gene therapy applications and as a potent vaccine vector.

Instrument-assisted soft tissue mobilization (IASTM) techniques use specialized hand-held instruments for applying controlled mechanical forces to the body with the goal of facilitating healing, improving range of motion, and reducing pain. Nevertheless, an optimal range of forces for achieving clinical outcomes has yet to be established. A barrier to advancing research on IASTM force optimization is the lack of commercially available instruments that quantify treatment forces. The aim of the current study was to assess the feasibility of attaching a flexible force sensor to a commercially available IASTM instrument to obtain valid force measurements. The validity of this novel approach was assessed by comparing data between the flexible force sensor and a force plate during a simulated treatment. Intraclass correlation coefficients, linear regression models, and Bland Altman plots all indicated excellent agreement between the force plate and flexible sensor when the instrument was used at 45°, 65°, and 90° treatment angles. Agreement between measures decreased when the instrument was held at 30°. Thus, commercially available instruments with attached sensors could make force measurement more accessible and feasible for a wider range of research settings, facilitating the advancement of IASTM research and ultimately informing clinical decision-making to improve patient care.

Abstract Background A shortage of healthcare providers, particularly in primary care and mental health, exists in the predominately rural state of Idaho. There are also barriers to retaining healthcare providers to work in rural and remote communities. Limited research using U.S. samples has explored factors that may affect the retention of healthcare providers in rural areas. Additionally, due to differences between communities, it is important to conduct community-level investigations to better understand how these factors may affect retention in rural areas. Therefore, the purpose of this study was to explore factors affecting healthcare provider retention in a rural community in Northern Idaho. Methods A modified version of the Nursing Community Apgar Questionnaire (NCAQ) was completed by 30 healthcare providers in a rural and frontier community in Northern Idaho to assess factors influencing healthcare provider retention. Factors were classified into classes including geographic, economic, scope of practice, medical support, and facility and community support classes. Retention factors were assessed on their perceived importance to retention as well as whether they were perceived as an advantage or challenge to retention based on Likert scales. A “Community Apgar” score was also created by combining the importance and advantage/challenge factors. Results Overall, items in the medical support group had the highest importance of any other class and included factors such as nursing workforce. Additionally, the facility and community support class, which included factors such as televideo support, was rated the highest advantage class and had the highest Apgar score, indicating it contained the factor that healthcare providers identified as the most important advantage (i.e., medical reference resources). Conclusion Our study identified multiple factors that healthcare providers deemed as important advantages or disadvantages to retaining healthcare providers in rural areas. Overall, facility and community support factors were found to have the highest advantage in the retention of rural providers. Rural healthcare organizations looking to increase healthcare provider retention should target retention efforts towards these factors. Additional research should also be conducted on other rural samples across the U.S. to make comparisons of findings.

Abstract Background The field of point-of-care ultrasound (POCUS) has advanced in recent decades due to the benefits it holds for medical providers. However, aspiring POCUS practitioners require adequate training. Unfortunately, there remains a paucity of resources to deliver this training, particularly in rural and underserved areas. Despite these barriers, calls for POCUS training in undergraduate medical education are growing, and many medical schools now deliver some form of POCUS education. Our program lacked POCUS training; therefore, we developed and implemented a POCUS curriculum for our first-year medical students. Methods We developed a POCUS curriculum for first year medical students in a rural medically underserved region of the United States. To evaluate our course, we measured learning outcomes, self-reported confidence in a variety of POCUS domains, and gathered feedback on the course with a multi-modal approach: an original written pre- and post-test, survey tool, and semi-structured interview protocol, respectively. Results Student (n=24) knowledge of POCUS significantly increased (pre-test average score = 55%, post-test average score = 79%, P

Greenly synthesized nanoparticles have garnered attention due to their low environmental footprint, but impurities limit their applications. A novel semi-organic method for synthesizing silver nanoparticles (AgNPs) using bio-based chelating fuels (Beta vulgaris subsp., Spinacia oleracea, and Ipomoea batatas) reduces the undesirable impurities. The study also showcases the impact of bio-based chelating fuel on various characteristics of AgNPs in comparison to synthetic chelating fuel. The antimicrobial efficacy of the synthesized AgNPs in conjunction with honey was also assessed against E. coli. The XRD analysis showed cubic structure of AgNPs. The FESEM and TEM analysis showed that the well-connected spherical-shaped AgNPs (∼3–120 nm diameter) while EDS confirmed the presence of Ag in all samples. The TEM analysis also revealed layers of carbonates in AgNPs synthesized using bio-based chelating fuels. XPS investigation confirmed the absence of any prominent impurities in prepared samples and AgNPs have not experienced oxidation on their surface. However, notable surface charging effects due to the uneven conductivity of the particles were observed. The broth dilution method showed that all mixtures containing AgNPs in combination with honey exhibited a significant bacterial growth reduction over a period of 120 h. The highest growth reduction of ∼75 % is obtained for the mixture having AgNPs (Ipomoea batatas) while the least growth reduction of ∼51 % is obtained for the mixture having AgNPs (Beta vulgaris subsp.). The findings affirm that AgNPs can be successfully synthesized using bio-based chelating fuels with negligible ecological consequences and devoid of contaminants. Moreover, the synthesized AgNPs can be employed in conjunction with honey for antibacterial purposes.

Objectives The primary purpose of the study was to assess the one-factor and two-factor structure of the Injury Psychological Readiness to Return to Sport Scale (IPRRS) in an injured physically active population using confirmatory factor analysis (CFA) procedures and assess group (ie, sex, age, injury type, athlete status) and longitudinal differences using structural equation modelling (eg, invariance testing).Methods The non-experimental study included a sample of 629 physically active individuals who suffered a musculoskeletal injury who sought treatment at an outpatient integrated sport medicine and rehabilitation therapy clinic. Participants filled out a questionnaire packet at three time points. Data analysis included a CFA and multigroup and longitudinal invariance.Results Sample mean age was 26.3 years, with females comprising 49.5%. Chronic injuries represented 29.6% of the sample and 35.0% were classified as competitive athletes. A six-item, one-factor model was confirmed in the sample with factor loadings ranging from 0.67 to 0.86. Multigroup and longitudinal invariance were established. Multigroup invariance demonstrated null differences between sex and injury type, and statistical differences between age and athlete status subgroups. Longitudinal invariance demonstrated a statistically significant increase in psychological readiness over time.Conclusions The findings support the use of the IPRRS as a tool to measure aspects of psychological readiness. Clinicians and researchers can use the IPRRS to assess interventions in future research.

BackgroundHeightened stress and insufficient sleep are common in the transition to college, often co-occur, and have both been linked to negative health outcomes. A challenge concerns disentangling whether perceived stress precedes or succeeds changes in sleep. These day-to-day associations may vary across individuals, but short study periods and group-level analyses in prior research may have obscured person-specific phenotypes. ObjectiveThis study aims to obtain stable estimates of lead-lag associations between perceived stress and objective sleep duration in the individual, unbiased by the group, by developing an individual-level linear model that can leverage intensive longitudinal data while remaining parsimonious. MethodsIn total, 55 college students (n=6, 11% second-year students and n=49, 89% first-year students) volunteered to provide daily self-reports of perceived stress via a smartphone app and wore an actigraphy wristband for the estimation of daily sleep duration continuously throughout the academic year (median usable daily observations per participant: 178, IQR 65.5). The individual-level linear model, developed in a Bayesian framework, included the predictor and outcome of interest and a covariate for the day of the week to account for weekly patterns. We validated the model on the cohort of second-year students (n=6, used as a pilot sample) by applying it to variables expected to correlate positively within individuals: objective sleep duration and self-reported sleep quality. The model was then applied to the fully independent target sample of first-year students (n=49) for the examination of bidirectional associations between daily stress levels and sleep duration. ResultsProof-of-concept analyses captured expected associations between objective sleep duration and subjective sleep quality in every pilot participant. Target analyses revealed negative associations between sleep duration and perceived stress in most of the participants (45/49, 92%), but their temporal association varied. Of the 49 participants, 19 (39%) showed a significant association (probability of direction>0.975): 8 (16%) showed elevated stress in the day associated with shorter sleep later that night, 5 (10%) showed shorter sleep associated with elevated stress the next day, and 6 (12%) showed both directions of association. Of note, when analyzed using a group-based multilevel model, individual estimates were systematically attenuated, and some even reversed sign. ConclusionsThe dynamic interplay of stress and sleep in daily life is likely person specific. Paired with intensive longitudinal data, our individual-level linear model provides a precision framework for the estimation of stable real-world behavioral and psychological dynamics and may support the personalized prioritization of intervention targets for health and well-being.

Objective: Centers for Medicare and Medicaid Services (CMS) has requested hospitals collect and report patient-reported outcomes (PROs) beginning in 2024 including the Hip Disability and Osteoarthritis Outcome Score Joint Replacement (HOOS-JR). However, scale structural validity of the HOOS-JR has minimally been assessed. The purpose of this study was to assess internal consistency, structural validity, and multi-group invariance properties of the HOOS-JR in a large sample of patients who underwent a total hip arthroplasty (THA). Methods: A cross-sectional study using the Surgical Outcomes System was retrospectively queried for patients who underwent a THA. Internal consistency was assessed using Cronbach's alpha and McDonald's Omega. A confirmatory factor analysis (CFA) was performed on the HOOS-JR using a priori cut-off values. Multi-group invariance testing was also performed on the sample of patients across sex and age groups. Results: Internal consistency was acceptable for 6-item (alpha ​= ​0.88; omega ​= ​0.88) and 5-item (alpha ​= ​0.86; omega ​= ​0.86) HOOS-JR. The one-factor, 6-item CFA did not meet the recommended fit indices. The one-factor, 5-item CFA had acceptable fit for the sample data. Invariance testing criteria were met between the age groups; however, scalar invariance was not met for sex. Conclusion: The 6-item HOOS-JR did not meet contemporary model fit indices indicating that scale refinement is warranted. The 5-item met most goodness-of-fit indices and invariance criteria. However, further scale refinement may be warranted as localized fit issues were identified.

A nanostructured material, ordered mesoporous carbon (OMC), was synthesised in metal- and halide-free form and its use for the sequestration of crystal violet, a hazardous triphenylmethane dye, is reported for the first time. The OMC material is characterised using scanning transmission electron microscopy with energy-dispersive spectroscopy for chemical analysis, by Fourier-transform infrared spectroscopy, and by nitrogen gas physisorption. The ideal conditions for the uptake of crystal violet dye were determined in batch experiments covering the standard parameters: pH, concentration, contact time, and adsorbent dosage. Experimental data are validated by applying Langmuir, Freundlich, Dubinin–Radushkevich, and Temkin isotherms. The thermodynamic parameters, ΔH°, ΔG°, and ΔS°, are calculated and it has been found that the adsorption process is spontaneous and endothermic with increasing disorder. An in-depth analysis of the kinetics of the adsorption process, order of the reaction and corresponding values of the rate constants was performed. The adsorption of crystal violet over OMC has been found to follow pseudo-second-order kinetics through a film diffusion process at all temperatures studied. Continuous flow column operations were performed using fixed bed adsorption. Parameters including percentage saturation of the OMC bed are evaluated. The exhausted column was regenerated through a desorption process and column efficiency was determined.

This study investigated the association between self-compassion and psychological pain across various demographic variables. Using canonical correlation analysis, we observed an inverse relationship between the combined factors of the Self-Compassion Scale (SCS) and the Orbach and Mikulincer Mental Pain Scale (OMMP-8). Subgroup analyses revealed differences in SCS subscales among demographic groups with females, individuals with mental health diagnoses, and non-athletes displaying higher scores on negative SCS subscales and PsyPn. Injury status did not significantly affect self-compassion levels, although injured individuals scored higher on the irreversibility subscale of PsyPn. Negative SCS factors exhibited larger group differences and stronger correlations with PsyPn, indicating the potency of negative thinking in influencing psychological pain. These findings underscore the importance of self-compassion in mental health and suggest potential implications for intervention strategies.

Vesiculoviruses are attractive oncolytic virus platforms due to their rapid replication, appreciable transgene capacity, broad tropism, limited preexisting immunity, and tumor selectivity through type I interferon response defects in malignant cells. We developed a synthetic chimeric virus (VMG) expressing the glycoprotein (G) from Morreton virus (MorV) and utilizing the remaining structural genes from vesicular stomatitis virus (VSV). VMG exhibited in vitro efficacy by inducing oncolysis in a broad range of sarcoma subtypes across multiple species. Notably, all cell lines tested showed the ability of VMG to yield productive infection with rapid replication kinetics and induction of apoptosis. Furthermore, pilot safety evaluations of VMG in immunocompetent, non-tumor-bearing mice showed an absence of toxicity with intranasal doses as high as 1e10 50% tissue culture infectious dose (TCID50)/kg. Locoregional administration of VMG in vivo resulted in tumor reduction in an immunodeficient Ewing sarcoma xenograft at doses as low as 2e5 TCID50. In a murine syngeneic fibrosarcoma model, while no tumor inhibition was achieved with VMG, there was a robust induction of CD8+ T cells within the tumor. The studies described herein establish the promising potential for VMG to be used as a novel oncolytic virotherapy platform with anticancer effects in sarcoma.

Recently we found compelling evidence for a gravitational-wave background with Hellings and Downs (HD) correlations in our 15 yr data set. These correlations describe gravitational waves as predicted by general relativity, which has two transverse polarization modes. However, more general metric theories of gravity can have additional polarization modes, which produce different interpulsar correlations. In this work, we search the NANOGrav 15 yr data set for evidence of a gravitational-wave background with quadrupolar HD and scalar-transverse (ST) correlations. We find that HD correlations are the best fit to the data and no significant evidence in favor of ST correlations. While Bayes factors show strong evidence for a correlated signal, the data does not strongly prefer either correlation signature, with Bayes factors ∼2 when comparing HD to ST correlations, and ∼1 for HD plus ST correlations to HD correlations alone. However, when modeled alongside HD correlations, the amplitude and spectral index posteriors for ST correlations are uninformative, with the HD process accounting for the vast majority of the total signal. Using the optimal statistic, a frequentist technique that focuses on the pulsar-pair cross-correlations, we find median signal-to-noise ratios of 5.0 for HD and 4.6 for ST correlations when fit for separately, and median signal-to-noise ratios of 3.5 for HD and 3.0 for ST correlations when fit for simultaneously. While the signal-to-noise ratios for each of the correlations are comparable, the estimated amplitude and spectral index for HD are a significantly better fit to the total signal, in agreement with our Bayesian analysis.

# BACKGROUND Improving single leg squat (SLS) movement symmetry may benefit rehabilitation protocols. The Total Motion Release® (TMR®) protocol has been theorized to evaluate and improve patient-perceived movement asymmetries. # HYPOTHESIS/PURPOSE The purpose of this study was to evaluate whether perceived asymmetries identified by a TMR® scoring protocol were related to biomechanical asymmetries and whether improving perceived asymmetries influenced movement mechanics. It was hypothesized that participants with perceived asymmetries would also present with biomechanical asymmetries. A secondary hypothesis was that participants would reduce their perceived asymmetries after performing the TMR® protocol and subsequently have greater biomechanical symmetry. # STUDY DESIGN Descriptive Cohort (Laboratory Study). # METHODS Twenty participants (10 female, 10 male) with self-identified bilateral differences of 10 points or greater on the TMR® scoring scale were recruited for the study. The non-preferred side was defined as the side that scored higher. 3Dimensional motion capture was used to bilaterally assess baseline SLS depth as well as hip, knee, and ankle kinematics and kinetics. For the TMR® protocol, sets of 10 SLSs were performed on the preferred leg until their perceived asymmetries were resolved (i.e., both sides scored equally), or four sets had been completed. Kinematics and kinetics were collected immediately after the intervention and after a 10-minute rest period. # RESULTS Participants had biomechanical asymmetries at baseline for knee flexion, ankle flexion, and knee moments. Following the intervention, participants had reduced TMR® scores on the non-preferred leg, and this coincided with increased knee joint moments on that side. Although perceived asymmetries were resolved after the intervention, kinematic and kinetic asymmetries at the knee and ankle were still present. # CONCLUSIONS A TMR® intervention could benefit rehabilitation protocols by reducing factors of dysfunction and increasing the ability of patients to load the non-preferred knee. Further investigations are necessary to elucidate the importance of asymmetrical movement patterns. # LEVEL OF EVIDENCE 3b

Abstract Introduction Idaho is a medically underserved and rural state comprised mostly health professional shortage areas for primary and specialty care. Given the state shortages and barriers to access care, the testing and treatment of COVID‐19 may be improved through the implementation of telementoring education programs such as Project Extension for Community Healthcare Outcomes (ECHO). The purpose of this article was to assess session attendance and self‐reported healthcare clinician perceptions of the ECHO Idaho COVID‐19 series (2020 and 2021), a modified Project ECHO model provided during the COVID‐19 pandemic in Idaho. Methods ECHO Idaho developed a COVID‐19 ECHO series for healthcare providers to attend in 2020 and 2021. The sessions included COVID‐19 updates specific to Idaho, didactic presentations on prevention, screening, diagnosis, and evidence‐based treatments for COVID‐19, and case‐based presentations. Results A total of 664 individuals attended the 2020 series and 260 individuals attended the 2021 series, with 1752.5 continuing medical education hours being claimed. Participants reported series participation increased overall knowledge of COVID‐19, knowledge of best practices for treatment, and awareness of resources available in Idaho. Further, series participation was perceived to reduce feelings of isolation, enhance access to information, and support healthcare professionals (e.g., provided resources) during the pandemic. Conclusion Results of this evaluation indicate that the ECHO Idaho COVID‐19 series was a useful and valuable program to implement during a pandemic in a rural and frontier state to improve physician knowledge and specialty training.

Background: Idaho, a predominately rural state, has a high prevalence of mental illness with minimal access to care. Barriers in diagnosis and treatment of pediatric behavioral health disorders could be mitigated with an accessible and effective specialty training program. Methods: A 10-session Project Extension for Community Health Outcomes (ECHO) series was designed to expand provider knowledge about pediatric behavioral health conditions and improve perceived clinical practice skills. Pre- and postseries evaluation surveys and individual session evaluations were used to assess the program. Results: A total of 148 individuals attended at least 1 of the 10 sessions. Participants reported high satisfaction with individual sessions and indicated that attendance positively impacted their knowledge and competency. Participants also reported that the knowledge and skills gained from the series would benefit more than half of their patients or clients. Conclusion: The short ECHO series appears to be a viable and valuable option to provide Idaho providers with effective specialty training that is well attended and well received.

This study explores the detailed characterization of a biosorbent (Hen Feather) and its efficient use in eradicating the azo dye Metanil Yellow (MY) from its aqueous solutions. Effects of a range of experimental parameters, including pH, initial dye concentration, biosorbent dosage and contact time on the adsorption, were studied. A detailed physical and chemical characterization of the biosorbent was made using SEM, XRD, XPS and FTIR. During the optimization of adsorption parameters, the highest dye uptake of almost 99% was recorded at pH 2, dye concentration 2 × 10−5 M, 0.05 g of biosorbent and a contact period of 75 min. Various adsorption isotherm models were studied to gather different adsorption and thermodynamic parameters. The linearity of the Langmuir, Freundlich and D-R adsorption isotherms indicate homogeneous, multilayer chemisorption with high adsorption affinity between the dye and biosorbent. Values of the changes in the Gibbs free energy (ΔG°) and the enthalpy (ΔH°) of the adsorption process have been calculated, these values indicate that it is a spontaneous and endothermic process. Kinetics of the adsorption were also measured, and it was established that the adsorption of MY over Hen Feather follows a pseudo-second-order kinetic model at temperatures 30, 40 and 50 °C. The findings of this investigation clearly indicate that the studied biosorbent exhibits a high affinity towards the dye (MY), and it can be effectively, economically and efficiently used to sequestrate and eradicate MY from its aqueous solutions.

Four ceria-based mesoporous oxide materials were prepared using a new vacuum impregnation (VI) templating method developed by the authors, namely, vacuum-assisted nanocasting (VAN). Two hard templates (SBA-15 and KIT-6) were employed, and products with compositions CeO2 and Ce0.9Gd0.1O1.9 (CGO) were made with each. The desired fluorite phase and composition were confirmed by powder XRD and EDS. The product structures were characterised by XRD, TEM, gas physisorption and SAXS. All products contained ordered mesoporous material in high yields. The specific surface areas (SSAs) and pore volumes of the products were determined to be high and the pore size and pore spacings related well to the templates from which the materials were synthesised. The TEM studies confirmed that the samples had a 3D pore structure, with this being the negative of the original template. The target materials were not only produced in high yields, but also displayed a porous single-crystal morphology with non-linear lattice planes. The highest SSA values and pore volumes were reported for materials impregnated using the KIT-6 template and with the CGO composition. The results suggest that VAN is an excellent and reproducible method for producing ordered mesoporous cerias and has considerable potential for wider application. All the mesoporous products showed dramatically increased reducibility in TPR experiments compared with a high-SSA nanoparticulate ceria reference. This is very promising for their potential applications in oxidation catalysts and in fuel cell components.

# Background The Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) is a seven-item patient reported outcome measure used to assess perceived knee health. Though commonly used, the longitudinal psychometric properties of the KOOS-JR have not been established and further characterization of its structural validity and multi-group invariance properties is warranted. # Purpose The purpose of this study was to evaluate psychometric properties of the KOOS-JR in a large sample of patients who received care for knee pathology. # Study Design Original research. # Methods Longitudinal data extracted from the Surgical Outcome System (SOS) database of 13,470 knee pathology patients who completed the KOOS-JR at baseline, three-months, six- months, and one-year. Scale structure was assessed with confirmatory factor analysis (CFA), while multi-group and longitudinal invariance properties were assessed with CFA-based procedures. Latent group means were compared with statistical significance set at α ≤ .05 and Cohen’s d effect size as d = 0.2 (small), d = 0.5 (medium), and d = 0.8 (large). # Results CFA results exceeded goodness-of-fit indices at all timepoints. Multi-group invariance properties passed test requirements. Longitudinal analysis identified a biased item resulting in removal of item #1; the retained six-item model (KOOS-JR-6) passed longitudinal invariance requirements. KOOS-JR-6 scores significantly changed over time (p ≤ .001, Mdiff = 1.08, Cohen’s d = 0.57): the highest scores were at baseline examination and the lowest at 12-month assessment. # Conclusions The KOOS-JR can be used to assess baseline differences between males and females, middle and older aged adults, and patients receiving total knee arthroplasty or non-operative care. Caution is warranted if the KOOS-JR is used longitudinally due to potential measurement error associated with item #1. The KOOS-JR-6 may be a more viable option to assess change over time; however, more research is warranted. # Level of Evidence 3 © The Author(s)

X-linked hypophosphatemia (XLH) is characterized by high serum fibroblast growth factor 23 (FGF23) levels, resulting in impaired 1,25-dihydroxyvitamin D3 (1,25D) production. Adults with XLH develop a painful mineralization of the tendon-bone attachment site (enthesis), called enthesopathy. Treatment of mice with XLH (Hyp) with 1,25D or an anti–FGF23 Ab, both of which increase 1,25D signaling, prevents enthesopathy. Therefore, we undertook studies to determine a role for impaired 1,25D action in enthesopathy development. Entheses from mice lacking vitamin D 1α-hydroxylase (Cyp27b1) (C–/–) had a similar enthesopathy to Hyp mice, whereas deletion of Fgf23 in Hyp mice prevented enthesopathy, and deletion of both Cyp27b1 and Fgf23 in mice resulted in enthesopathy, demonstrating that the impaired 1,25D action due to high FGF23 levels underlies XLH enthesopathy development. Like Hyp mice, enthesopathy in C–/– mice was observed by P14 and was prevented, but not reversed, with 1,25D therapy. Deletion of the vitamin D receptor in scleraxis-expressing cells resulted in enthesopathy, indicating that 1,25D acted directly on enthesis cells to regulate enthesopathy development. These results show that 1,25D signaling was necessary for normal postnatal enthesis maturation and played a role in XLH enthesopathy development. Optimizing 1,25D replacement in pediatric patients with XLH is necessary to prevent enthesopathy.

Abstract The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored.

The single leg squat (SLS), forward step down (FSD), and lateral step down (LSD) are clinically reliable movement screens for identifying motion imbalances. The current understanding for the kinematic profiles of each task is limited to discrete time points such as peak knee flexion. However, analyses of the entire movement would better aid clinicians when selecting the appropriate task for rehabilitation or movement screen purposes. The current study used Statistical Parametric Mapping to ascertain differences in the kinematic waveforms for the entire duration of each task. The trunk, pelvis, hip, and knee were analyzed in the sagittal and frontal planes. Data for each variable and task were analyzed from 0–100% of the movement. Primary findings indicated that the FSD provoked a greater magnitude of knee abduction than the SLS and LSD from 26–66% of the movement. The SLS generated the greatest amounts of trunk, pelvic, and hip flexion for the entirety of the movement. The LSD elicited the least amount of ipsilateral trunk lean (90–100%). Thus, the FSD may be optimal for assessing frontal plane knee motion as a screen for injury risk, while the SLS has potential to place increased sagittal plane demand on the muscles of the hip.

Safety and efficacy of vaccines against the SARS-CoV-2 coronavirus has been demonstrated in clinical trials and next by their real world use through the course of the ongoing COVID-19 pandemic. However, very rare adverse events have been detected post-authorization in certain parts of the world. This meeting report summarizes an EMA workshop’s discussion on the epidemiology, clinical presentation and biology of thrombosis with thrombocytopenia syndrome after adenovirus vector COVID-19 vaccination. General agreement was reached by international regulators, scientists and developers on the steps needed to fill the gaps in the characterization of this new syndrome. In particular, actions should be taken to improve the post-vaccination surveillance activities in low and middle income countries and investigate potential genetic predisposition factors.

# Background The International Knee Document Committee Subjective Knee Form (IKDC-SKF) is a patient-reported outcome measure used in orthopedics and sports medicine. Further psychometric assessment is necessary to confirm measurement properties in a large, heterogenous sample. # Purpose The purpose of the study was to assess the psychometric properties of the IKDC-SKF in a large, heterogenous sample. # Study Design Cross-Sectional Study # Methods An exploratory factor analysis (EFA) was conducted to identify a sound latent structure and to assess internal consistency in a large sample of patients who underwent knee arthroscopy. A confirmatory factor analysis (CFA) was conducted to confirm structural validity. Multi-group invariance was conducted to assess factorial stability across sex and age groups, while longitudinal invariance procedures were performed to assess stability over time. # Results A 3-factor, 9-item IKDC-SKF short form was identified with EFA procedures. The model was confirmed with CFA (CFI = 0.983; TLI = 0.975; IFI = 0.983; RMSEA = 0.057), while a sound 2-factor, 6-item model was also identified (CFI = 1.0; TLI = 0.999; IFI = 1.0; RMSEA = 0.11). The 9-item IKDC-SKF short form was invariant across groups but not time; removal of a single item (i.e., 8-item IKDC-SKF short form) resulted in longitudinal invariance. The 6-item IKDC-SKF short form was invariant across groups and time. # Conclusion The 6-item, 8-item, and 9-item short form versions of the IKDC-SKF exceed contemporary fit recommendations and present as plausible alternatives to the IKDC-SKF with improved measurement properties, reduced scale response burden, and evidence of multi-group and longitudinal invariance. Further, the 6- and 8-item IKDC-SKF short forms may be used to assess group differences or change across time. # Level of evidence here Level 3

Collaborative neuroimaging research is often hindered by technological, policy, administrative, and methodological barriers, despite the abundance of available data. COINSTAC (The Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation) is a platform that successfully tackles these challenges through federated analysis, allowing researchers to analyze datasets without publicly sharing their data. This paper presents a significant enhancement to the COINSTAC platform: COINSTAC Vaults (CVs). CVs are designed to further reduce barriers by hosting standardized, persistent, and highly-available datasets, while seamlessly integrating with COINSTAC's federated analysis capabilities. CVs offer a user-friendly interface for self-service analysis, streamlining collaboration, and eliminating the need for manual coordination with data owners. Importantly, CVs can also be used in conjunction with open data as well, by simply creating a CV hosting the open data one would like to include in the analysis, thus filling an important gap in the data sharing ecosystem. We demonstrate the impact of CVs through several functional and structural neuroimaging studies utilizing federated analysis showcasing their potential to improve the reproducibility of research and increase sample sizes in neuroimaging studies.

Many transgender and gender diverse (trans) people use hormone therapy for gender-affirmation. Some trans people obtain hormone therapy without prescriptions from clinicians—a practice called “do-it-yourself hormone therapy” (DIY HT). When patients using DIY HT seek formal medical care, patient-clinician communication challenges arise. In an effort to explore these challenges and improve patient-clinician communication, we conducted qualitative interviews with 20 U.S.-based trans people who had practiced DIY HT. We performed a thematic analysis guided by Goldsmith's Normative Rhetorical Theory. We generated two themes regarding the dilemmas patients face when (not) communicating about DIY HT with clinicians. First, I want a clinician who is a partner, not a gatekeeper, describes patients' difficulties partnering with clinicians who often create barriers to accessing hormone therapy. Second, I (don't) want to be honest, describes a tension patients reported; patients desired honest communication with clinicians, but feared that disclosing DIY HT use would cause them to be stigmatized and labeled ‘non-compliant.’ We also developed two themes regarding trans patients' recommendations for clinicians. First, create respectful and inclusive clinic spaces, suggests that clinicians can demonstrate respect for trans identities by displaying pride flags, and asking for patients' pronouns and name they go by on intake forms. Second, share decision-making with patients, suggests that clinicians can build alliances with trans patients by communicating their desire to openly discuss, assess, and mutually agree upon hormone treatment plans. We offer strategies for how clinicians can practice patient-centered care and build partnerships with trans patients when communicating about hormone therapy.

Pulsar timing arrays (PTAs) are designed to detect low-frequency gravitational waves (GWs). GWs induce achromatic signals in PTA data, meaning that the timing delays do not depend on radio frequency. However, pulse arrival times are also affected by radio-frequency-dependent “chromatic” noise from sources such as dispersion measure (DM) and scattering delay variations. Furthermore, the characterization of GW signals may be influenced by the choice of chromatic noise model for each pulsar. To better understand this effect, we assess if and how different chromatic noise models affect the achromatic noise properties in each pulsar. The models we compare include existing DM models used by the North American Nanohertz Observatory for Gravitational waves (NANOGrav) and noise models used for the European PTA Data Release 2 (EPTA DR2). We perform this comparison using a subsample of six pulsars from the NANOGrav 15 yr data set, selecting the same six pulsars as from the EPTA DR2 six-pulsar data set. We find that the choice of chromatic noise model noticeably affects the achromatic noise properties of several pulsars. This is most dramatic for PSR J1713+0747, where the amplitude of its achromatic red noise lowers from ${\mathrm{log}}_{10}{A}_{\mathrm{RN}}=-{14.1}_{-0.1}^{+0.1}$ to $-{14.7}_{-0.5}^{+0.3}$ , and the spectral index broadens from ${\gamma }_{\mathrm{RN}}={2.6}_{-0.4}^{+0.5}$ to ${\gamma }_{\mathrm{RN}}={3.5}_{-0.9}^{+1.2}$ . We also compare each pulsar's noise properties with those inferred from the EPTA DR2, using the same models. From the discrepancies, we identify potential areas where the noise models could be improved. These results highlight the potential for custom chromatic noise models to improve PTA sensitivity to GWs.

Machine learning (ML) based interatomic potentials have transformed the field of atomistic materials modelling. However, ML potentials depend critically on the quality and quantity of quantum-mechanical reference data with which they are trained, and therefore developing datasets and training pipelines is becoming an increasingly central challenge. Leveraging the idea of ‘synthetic’ (artificial) data that is common in other areas of ML research, we here show that synthetic atomistic data, themselves obtained at scale with an existing ML potential, constitute a useful pre-training task for neural-network (NN) interatomic potential models. Once pre-trained with a large synthetic dataset, these models can be fine-tuned on a much smaller, quantum-mechanical one, improving numerical accuracy and stability in computational practice. We demonstrate feasibility for a series of equivariant graph-NN potentials for carbon, and we carry out initial experiments to test the limits of the approach.

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational-wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within 1 σ . The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we “extended” each PTA’s data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings–Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA’s Data Release 3, which will involve not just adding in additional pulsars but also including data from all three PTAs where any given pulsar is timed by more than a single PTA.

The millisecond pulsar J1713+0747 underwent a sudden and significant pulse shape change between 2021 April 16 and 17 (MJDs 59320 and 59321). Subsequently, the pulse shape gradually recovered over the course of several months. We report the results of continued multifrequency radio observations of the pulsar made using the Canadian Hydrogen Intensity Mapping Experiment and the 100 m Green Bank Telescope in a 3 yr period encompassing the shape change event, between 2020 February and 2023 February. As of 2023 February, the pulse shape had returned to a state similar to that seen before the event, but with measurable changes remaining. The amplitude of the shape change and the accompanying time-of-arrival residuals display a strong nonmonotonic dependence on radio frequency, demonstrating that the event is neither a glitch (the effects of which should be independent of radio frequency, ν ) nor a change in dispersion measure alone (which would produce a delay proportional to ν ^−2 ). However, it does bear some resemblance to the two previous “chromatic timing events” observed in J1713+0747, as well as to a similar event observed in PSR J1643−1224 in 2015.

The radio galaxy 3C 66B has been hypothesized to host a supermassive black hole binary (SMBHB) at its center based on electromagnetic observations. Its apparent 1.05 yr period and low redshift (∼0.02) make it an interesting testbed to search for low-frequency gravitational waves (GWs) using pulsar timing array (PTA) experiments. This source has been subjected to multiple searches for continuous GWs from a circular SMBHB, resulting in progressively more stringent constraints on its GW amplitude and chirp mass. In this paper, we develop a pipeline for performing Bayesian targeted searches for eccentric SMBHBs in PTA data sets, and test its efficacy by applying it to simulated data sets with varying injected signal strengths. We also search for a realistic eccentric SMBHB source in 3C 66B using the NANOGrav 12.5 yr data set employing PTA signal models containing Earth term-only as well as Earth+pulsar term contributions using this pipeline. Due to limitations in our PTA signal model, we get meaningful results only when the initial eccentricity e _0 < 0.5 and the symmetric mass ratio η > 0.1. We find no evidence for an eccentric SMBHB signal in our data, and therefore place 95% upper limits on the PTA signal amplitude of 88.1 ± 3.7 ns for the Earth term-only and 81.74 ± 0.86 ns for the Earth+pulsar term searches for e _0 < 0.5 and η > 0.1. Similar 95% upper limits on the chirp mass are (1.98 ± 0.05) × 10 ^9 and (1.81 ± 0.01) × 10 ^9 M _☉ . These upper limits, while less stringent than those calculated from a circular binary search in the NANOGrav 12.5 yr data set, are consistent with the SMBHB model of 3C 66B developed from electromagnetic observations.

We present the results of a Bayesian search for gravitational wave (GW) memory in the NANOGrav 12.5 yr data set. We find no convincing evidence for any gravitational wave memory signals in this data set. We find a Bayes factor of 2.8 in favor of a model that includes a memory signal and common spatially uncorrelated red noise (CURN) compared to a model including only a CURN. However, further investigation shows that a disproportionate amount of support for the memory signal comes from three dubious pulsars. Using a more flexible red-noise model in these pulsars reduces the Bayes factor to 1.3. Having found no compelling evidence, we go on to place upper limits on the strain amplitude of GW memory events as a function of sky location and event epoch. These upper limits are computed using a signal model that assumes the existence of a common, spatially uncorrelated red noise in addition to a GW memory signal. The median strain upper limit as a function of sky position is approximately 3.3 × 10 ^−14 . We also find that there are some differences in the upper limits as a function of sky position centered around PSR J0613−0200. This suggests that this pulsar has some excess noise that can be confounded with GW memory. Finally, the upper limits as a function of burst epoch continue to improve at later epochs. This improvement is attributable to the continued growth of the pulsar timing array.

Oncolytic virotherapies (OV) hold immense clinical potential. OV based on human adenoviruses (HAdV) derived from HAdV with naturally low rates of pre-existing immunity will be beneficial for future clinical translation. We generated a low-seroprevalence HAdV-D10 serotype vector incorporating an αvβ6 integrin-selective peptide, A20, to target αvβ6-positive tumor cell types. HAdV-D10 has limited natural tropism. Structural and biological studies of HAdV-D10 knob protein highlighted low-affinity engagement with native adenoviral receptors CAR and sialic acid. HAdV-D10 fails to engage blood coagulation factor X, potentially eliminating “off-target” hepatic sequestration in vivo. We engineered an A20 peptide that selectively binds αvβ6 integrin into the DG loop of HAdV-D10 fiber knob. Assays in αvβ6+ cancer cell lines demonstrated significantly increased transduction mediated by αvβ6-targeted variants compared with controls, confirmed microscopically. HAdV-D10.A20 resisted neutralization by neutralizing HAdV-C5 sera. Systemic delivery of HAdV-D10.A20 resulted in significantly increased GFP expression in BT20 tumors. Replication-competent HAdV-D10.A20 demonstrated αvβ6 integrin-selective cell killing in vitro and in vivo. HAdV-D10 possesses characteristics of a promising virotherapy, combining low seroprevalence, weak receptor interactions, and reduced off-target uptake. Incorporation of an αvβ6 integrin-selective peptide resulted in HAdV-D10.A20, with significant potential for clinical translation.

Objective The purpose of this study was to examine whether the forces used by trained clinicians during a simulated instrument-assisted soft tissue mobilisation (IASTM) treatment varied across five different instruments during one-handed and two-handed IASTM grips.Methods Nine athletic trainers who previously completed IASTM training and used the technique in professional practice were included in the study. A skin simulant was attached to a force plate and used to evaluate force production during a simulated IASTM treatment scenario. Peak (Fpeak) and mean (Fmean) forces were recorded for both one-handed and two-handed grips for each participant across the five instruments. Data were analysed using separate 2 (grip type) × 5 (IASTM instrument) repeated measures analysis of variance for both Fpeak and Fmean.Results Data for Fpeak demonstrated a significant main effect for grip type (F(1, 8)=46.39, p

Abstract College students commonly experience psychological distress when faced with intensified academic demands and changes in the social environment. Examining the nature and dynamics of students’ affective and behavioral experiences can help us better characterize the correlates of psychological distress. Here, we leveraged wearables and smartphones to study 49 first-year college students continuously throughout the academic year. Affect and sleep, academic, and social behavior showed substantial changes from school semesters to school breaks and from weekdays to weekends. Three student clusters were identified with behavioral and affective dissociations and varying levels of distress throughout the year. While academics were a common stressor for all, the cluster with highest distress stood out by frequent report of social stress. Moreover, the frequency of reporting social, but not academic, stress predicted subsequent clinical symptoms. Two years later, during the COVID-19 pandemic, the first-year cluster with highest distress again stood out by frequent social stress and elevated clinical symptoms. Focus on sustained interpersonal stress, relative to academic stress, might be especially helpful to identify students at heightened risk for psychopathology.

Abstract Representing subgrid variabilities of land surface processes and their upscaled effects is crucial for global climate modeling. Here, we implement a multiple atmosphere multiple land (MAML) framework in the superparamaterized version of E3SM (SP‐E3SM) to explicitly simulate the subgrid variabilities of land states and fluxes at cloud‐resolving scale and their interactions with atmosphere. Comparing to the standard SP‐E3SM in which all the atmospheric columns of the cloud resolving model embedded within the global atmospheric model grid interact with the same land surface (i.e., multiple atmosphere single land (MASL)), the impact of MAML on the strength of land‐atmosphere coupling is limited, partly because the current implementation mainly facilitates one‐way coupling between the cloud‐resolving model and the land surface model. Despite such limitation, MAML increases the surface latent heat flux at the expense of sensible heat flux, and increases precipitation in India, Amazon, and Central Africa, reducing the model dry bias compared to the standard SP‐E3SM. By employing a normalized gross moist stability (NGMS) diagnostic framework, we find that the increase in precipitation minus evaporation (P‐E) is primarily driven by the change in large‐scale moisture convergence, particularly by the increase of water vapor in the lower atmosphere, while the local effect of total surface energy flux plays a minor role in the P‐E change. More specifically, MAML changes the surface energy partitioning (evaporative fraction), increases the atmosphere water vapor, and further increases P‐E by decreasing the NGMS. Finally, future development in the MAML framework is discussed.

# Background Hip Disability and Osteoarthritis Outcome Score (HOOS), HOOS-Joint Replacement (JR), HOOS Physical Function (PS), and HOOS-12 item scale have been suggested as reliable and valid instruments for assessing hip disability. However, factorial validity, invariance across subgroups, and repeated measures of the scale across different populations have not been well supported in the literature. # Purpose The primary study objectives were to: (1) assess model fit and psychometric properties of the original 40-item HOOS scale, (2) assess model fit of the HOOS-JR, (3) assess model fit of the HOOS-PS, and (4) assess model fit of the HOOS-12. A secondary objective was to perform multigroup invariance testing across physical activity level and hip pathology subgroups for models that met recommended fit indices. # Study Design Cross-Sectional Study # Methods Individual confirmatory factor analyses (CFAs) were conducted for the HOOS, HOOS-JR, HOOS-PS, and HOOS-12. Additionally, multigroup invariance testing (i.e., activity level, injury type) was conducted on the HOOS-JR and HOOS-PS. # Results Model fit indices did not meet contemporary recommendations for the HOOS and the HOOS-12. Model fit indices for the HOOS-JR and the HOOS-PS met some, but not all, contemporary recommendations. Invariance criteria was met for the HOOS-JR and HOOS-PS. # Conclusion The scale structure of the HOOS and HOOS-12 were not supported; however, preliminary evidence to support the scale structure of the HOOS-JR and HOOS-PS was found. Clinicians and researchers who utilize the scales should do so with caution due to their limitations and untested properties until further research establishes the full psychometric properties of these scales and recommendations for their continued use.

The North American Nanohertz Observatory for Gravitational Waves (NANOGrav) has reported evidence for the presence of an isotropic nanohertz gravitational-wave background (GWB) in its 15 yr data set. However, if the GWB is produced by a population of inspiraling supermassive black hole binary (SMBHB) systems, then the background is predicted to be anisotropic, depending on the distribution of these systems in the local Universe and the statistical properties of the SMBHB population. In this work, we search for anisotropy in the GWB using multiple methods and bases to describe the distribution of the GWB power on the sky. We do not find significant evidence of anisotropy. By modeling the angular power distribution as a sum over spherical harmonics (where the coefficients are not bound to always generate positive power everywhere), we find that the Bayesian 95% upper limit on the level of dipole anisotropy is ( C _l _=1 / C _l _=0 ) < 27%. This is similar to the upper limit derived under the constraint of positive power everywhere, indicating that the dipole may be close to the data-informed regime. By contrast, the constraints on anisotropy at higher spherical-harmonic multipoles are strongly prior dominated. We also derive conservative estimates on the anisotropy expected from a random distribution of SMBHB systems using astrophysical simulations conditioned on the isotropic GWB inferred in the 15 yr data set and show that this data set has sufficient sensitivity to probe a large fraction of the predicted level of anisotropy. We end by highlighting the opportunities and challenges in searching for anisotropy in pulsar timing array data.

The NANOGrav 15 yr data set shows evidence for the presence of a low-frequency gravitational-wave background (GWB). While many physical processes can source such low-frequency gravitational waves, here we analyze the signal as coming from a population of supermassive black hole (SMBH) binaries distributed throughout the Universe. We show that astrophysically motivated models of SMBH binary populations are able to reproduce both the amplitude and shape of the observed low-frequency gravitational-wave spectrum. While multiple model variations are able to reproduce the GWB spectrum at our current measurement precision, our results highlight the importance of accurately modeling binary evolution for producing realistic GWB spectra. Additionally, while reasonable parameters are able to reproduce the 15 yr observations, the implied GWB amplitude necessitates either a large number of parameters to be at the edges of expected values or a small number of parameters to be notably different from standard expectations. While we are not yet able to definitively establish the origin of the inferred GWB signal, the consistency of the signal with astrophysical expectations offers a tantalizing prospect for confirming that SMBH binaries are able to form, reach subparsec separations, and eventually coalesce. As the significance grows over time, higher-order features of the GWB spectrum will definitively determine the nature of the GWB and allow for novel constraints on SMBH populations.

Evidence for a low-frequency stochastic gravitational-wave background has recently been reported based on analyses of pulsar timing array data. The most likely source of such a background is a population of supermassive black hole binaries, the loudest of which may be individually detected in these data sets. Here we present the search for individual supermassive black hole binaries in the NANOGrav 15 yr data set. We introduce several new techniques, which enhance the efficiency and modeling accuracy of the analysis. The search uncovered weak evidence for two candidate signals, one with a gravitational-wave frequency of ∼4 nHz, and another at ∼170 nHz. The significance of the low-frequency candidate was greatly diminished when Hellings–Downs correlations were included in the background model. The high-frequency candidate was discounted due to the lack of a plausible host galaxy, the unlikely astrophysical prior odds of finding such a source, and since most of its support comes from a single pulsar with a commensurate binary period. Finding no compelling evidence for signals from individual binary systems, we place upper limits on the strain amplitude of gravitational waves emitted by such systems. At our most sensitive frequency of 6 nHz, we place a sky-averaged 95% upper limit of 8 × 10 ^−15 on the strain amplitude. We also calculate an exclusion volume and a corresponding effective radius, within which we can rule out the presence of black hole binaries emitting at a given frequency.

Pulsar timing array collaborations, such as the North American Nanohertz Observatory for Gravitational Waves (NANOGrav), are seeking to detect nanohertz gravitational waves emitted by supermassive black hole binaries formed in the aftermath of galaxy mergers. We have searched for continuous waves from individual circular supermassive black hole binaries using NANOGrav’s recent 12.5 yr data set. We created new methods to accurately model the uncertainties on pulsar distances in our analysis, and we implemented new techniques to account for a common red-noise process in pulsar timing array data sets while searching for deterministic gravitational wave signals, including continuous waves. As we found no evidence for continuous waves in our data, we placed 95% upper limits on the strain amplitude of continuous waves emitted by these sources. At our most sensitive frequency of 7.65 nHz, we placed a sky-averaged limit of h _0 < (6.82 ± 0.35) × 10 ^−15 , and h _0 < (2.66 ± 0.15) × 10 ^−15 in our most sensitive sky location. Finally, we placed a multimessenger limit of ${ \mathcal M }\lt (1.41\pm 0.02)\times {10}^{9}\,{M}_{\odot }$ on the chirp mass of the supermassive black hole binary candidate 3C 66B.