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Liza Grosman-Rimon,1 Linda Jorgoni,1 Jane Casey,2 Susan Tory,1 Dinesh Kumbhare,3 Jhanvi Solanki,1 Barbara E Collins,1 Pete Wegier1,4 1Humber River Health, Research Institute, Toronto, Canada; 2Tampa General Hospital, Tampa, FL, USA; 3Department of Medicine, Division of Physical Medicine and Rehabilitation, University Health Network, Toronto, Canada; 4University of Toronto, Institute of Health Policy, Management and Evaluation University of Toronto, Toronto, CanadaCorrespondence: Liza Grosman-Rimon, Humber River Health, 235 Wilson Ave, North York, Toronto, ON, M3M 0B2, Canada, Tel +1416-242-82109, Email l.grosman@hrh.caIntroduction: In the last decade, clinical alert systems were developed for clinical use, including patient deterioration and other urgent clinical situations. However, investigations focusing on digital pain alert systems to assess and manage pain on time in in-hospital patients are scarce. The objective of the study was to assess the implementation of digital pain alerts in the various departments of a community hospital.Methods: Administrative data from the year 2020 to 2023 were collected. Only data from cases when pain alert was activated were included. Data included pain alert activation frequency, pain alert response duration (time from pain alert activation to alert stop when medication was administered), the department from which the pain alert was activated.Results: There was a steady significant decrease in the mean pain alert response duration over time from 2020 to 2023. The department with the shortest pain alert response duration was the Department of Surgery, and Cardiology (252.76 ± 4.712). The longest time delay was in the ICU (463.27± 2.73 min) and at the Mental Health Department (440.59± 5.46 min) (p < 0.01). The pain alert response duration gradually decreased from 2020 to 2023, with decreases from the first year in all of the units/departments, except for the ICU. NPS scores at the start of the alert to 30 minutes after alert stop decreased significantly.Conclusion: Management of pain improved over time across the hospital, and in most of the departments, suggesting that with experience, digital pain alert systems have the potential to improve pain management by providing timely pain intervention.Keywords: digital pain alert, community hospital, pain management, command centre

Abstract Artificial intelligence (AI)-based computational tools for deriving digital behavioral markers are increasingly able to automatically detect clinically relevant patterns in mood and behavior through algorithmic analysis of continuously and passively collected data. The integration of these technologies into clinical care is imminent, most notably in clinical psychology and psychiatry but also other disciplines (e.g., cardiology, neurology, neurosurgery, pain management). Meanwhile, ethical guidelines for implementation are lacking, as are insights into what patients and caregivers want and need to know about these technologies to ensure acceptability and informed consent. In this work, we present qualitative findings from interviews with 40 adolescent patients and their caregivers examining ethical and practical considerations for translating these technologies into clinical care. We observed seven key domains (in order of salience) in stakeholders’ informational needs: (1) clinical utility and value; (2) evidence, explainability, evaluation and contestation; (3) accuracy and trustworthiness; (4) data security, privacy, and misuse; (5) patient consent, control, and autonomy; (6) physician-patient relationship; and (7) patient safety, well-being, and dignity. Drawing from these themes, we provide a checklist of questions, as well as suggestions and key challenges, to help researchers and practitioners respond to what stakeholders want to know when integrating these technologies into clinical care and research. Our findings inform participatory approaches to co-designing treatment roadmaps for using these AI-based tools for enhanced patient engagement, acceptability and informed consent.

Abstract The Colorado River drains about 8% of the conterminous United States, provides water for 40 million people, and is one of the most overallocated rivers in the world. As the upper Colorado River Basin (UCOL) contributes an estimated 92% of the total basin natural streamflow, knowledge of the location and amount of surface water withdrawals in the UCOL is important for managing the Colorado River system. Since the UCOL encompasses portions of five states, water use data are dispersed among numerous federal and state agency databases, and there is no centralized dataset that documents surface water use within the entire UCOL at a fine spatial and temporal resolution. This article presents an inventory of 1,358 major structures that divert surface water from and within the UCOL with corresponding daily time series withdrawal records from 1980 through 2022. Data compilation efforts, processing methods, and contents of this diversion database are documented, and summary information is provided.

Abstract A deep learning model using attention-based multiple instance learning (aMIL) and self-supervised learning (SSL) was developed to perform pathologic classification of neuroblastic tumors and assess MYCN-amplification status using H&E-stained whole slide images from the largest reported cohort to date. The model showed promising performance in identifying diagnostic category, grade, mitosis-karyorrhexis index (MKI), and MYCN-amplification with validation on an external test dataset, suggesting potential for AI-assisted neuroblastoma classification.

Background:. Vertebral body defects pose a significant challenge in spinal reconstructive surgery. Compression fractures of the vertebral corpus are typically treated with vertebral augmentation procedures. There are significant risks associated with the introduction of foreign material in the spine, including infection and pseudarthrosis. Vascularized bone grafts (VBGs) have become a popular alternative for spinal reconstruction in the last decade thanks to their robust blood supply and autologous nature. VBGs have been described predominantly for the reconstruction of posterior vertebral defects. The objective of this study is to describe a novel procedure for the reconstruction of vertebral corpus defects in the lumbar and distal thoracic spine. Methods:. This is a cadaveric anatomy study. The authors performed the novel surgical technique on an anonymized cadaveric donor in the prone position and recorded the procedure through clinical photography. Consent for the procedure and photography was obtained from the Center for Procedural Innovation. Results:. A 5-cm-long posterior iliac crest VBG (IC-VBG) was successfully harvested on a pedicle of the quadratus lumborum muscle. The VBG was rotated and mobilized anteromedially to the vertebral corpus. In this donor, the IC-VBG could be inset with minimal tension anywhere along the vertebral bodies of the spine from the L5 to the T9 level. Conclusions:. A rotated, anteromedially mobilized IC-VBG represents a novel technique for reconstruction of the anterior vertebral corpus of the lumbar and distal thoracic spine with a lower risk of infection and pseudarthrosis than reconstruction with foreign materials.

ABSTRACT Background When the SRY gene is present in a 46,XX fetus, some degree of testicular development is expected. Our laboratory performed prenatal genetic testing for a fetus that had screened positive for Y chromosome material by noninvasive prenatal screening (NIPS) but that had apparently typical female development by ultrasound imaging. The aim of this study was to determine the clinical relevance of the NIPS results. Methods We analyzed fetal material obtained via amniocentesis procedure by G‐banding, microarray, and fluorescence in situ hybridization (FISH). Optical genome mapping (OGM) was also performed. Results G‐band analysis revealed a normal 46,XX karyotype. Microarray and FISH analyses together detected an SRY+ gain of 5.7 Mb from terminal Yp that was translocated to terminal Xq, with a loss of 1.6 Mb from terminal Xq. The final karyotype was 46,X,der(X)t(X;Y)(q28;p11.2). Prenatal ultrasound and postnatal physical examination revealed apparently typical female genitalia. The Xq deletion encompassed a gene, IKBKG, that is sensitive to loss of function, suggesting that preferential inactivation of the derivative X chromosome allowed for typical female development. OGM software did not directly identify this translocation. Conclusion This case demonstrates how the SRY gene may be present in a 46,XX biological female without differences of sexual development.

Abstract Since the 5th Assessment Report of the Intergovernmental Panel on Climate Change (AR5) an extended concept of the energetic analysis of climate change including forcings, feedbacks and adjustment processes has become widely adopted. Adjustments are defined as processes that occur in response to the introduction of a climate forcing agent, but that are independent of global‐mean surface temperature changes. Most considered are the adjustments that impact the Earth energy budget and strengthen or weaken the instantaneous radiative forcing due to the forcing agent. Some adjustment mechanisms also impact other aspects of climate not related to the Earth radiation budget. Since AR5 and a following description by Sherwood et al. (2015, https://doi.org/10.1175/bams‐d‐13‐00167.1), much research on adjustments has been performed and is reviewed here. We classify the adjustment mechanisms into six main categories, and discuss methods of quantifying these adjustments in terms of their potentials, shortcomings and practicality. We furthermore describe aspects of adjustments that act beyond the energetic framework, and we propose new ideas to observe adjustments or to make use of observations to constrain their representation in models. Altogether, the problem of adjustments is now on a robust scientific footing, and better quantification and observational constraint is possible. This allows for improvements in understanding and quantifying climate change.

Abstract Aggregation of misfolded α-synuclein (α-syn) is a key characteristic feature of Parkinson’s disease (PD) and related synucleinopathies. The nature of these aggregates and their contribution to cellular dysfunction is still not clearly elucidated. We employed mass spectrometry-based total and phospho-proteomics to characterize the underlying molecular and biological changes due to α-syn aggregation using the M83 mouse primary neuronal model of PD. We identified gross changes in the proteome that coincided with the formation of large Lewy body-like α-syn aggregates in these neurons. We used protein-protein interaction (PPI)-based network analysis to identify key protein clusters modulating specific biological pathways that may be dysregulated and identified several mechanisms that regulate protein homeostasis (proteostasis). The observed changes in the proteome may include both homeostatic compensation and dysregulation due to α-syn aggregation and a greater understanding of both processes and their role in α-syn-related proteostasis may lead to improved therapeutic options for patients with PD and related disorders.

Abstract The mechanisms by which clouds impact the variability of the mid‐latitude atmosphere are poorly understood. We use an idealized, dry atmospheric model to investigate the relationship between Atmospheric Cloud Radiative Effects (ACRE) and annular mode persistence. We force the model with time‐varying diabatic heating that mimics the observed ACRE response to the Southern Annular Mode (SAM). Realistic ACRE forcing reduces annular mode persistence by 5 days (−16%), which we attribute to a weakening of low‐frequency eddy forcing via modified low‐level temperature gradients, though this effect is partly compensated by reduced frictional damping due to zonal wind anomalies becoming more top‐heavy. The persistence changes are nonlinear with respect to the amplitude of ACRE forcing, reflecting nonlinearities in the response of the eddy forcing. These results highlight the ACRE's impact on low‐frequency eddy forcing as the dominant cause of changes in annular mode persistence.

As technological advancements continue to redefine the landscape of adult education and training, virtual reality (VR) has emerged as a potent tool for enhancing skill acquisition. This literature review synthesizes existing research on the utilization of immersive and discrete VR in training adults in the medical domain. The primary focus was on understanding the effectiveness, challenges, and potential applications of VR-based training programs. Specifically, we reviewed studies related to practical skills critical to safety that target a non-surgical, discrete medical procedure (e.g., diabetes care procedures, how to correctly set a G-tube, CPR, correct personal protective equipment [PPE] usage) using an immersive VR technology as a training modality. Further, the studies reviewed had to include a comparison of immersive VR training to that of a business-as-usual (BAU) method. We conducted a review of the six studies that met the criteria and coded variables related to what technology was used, targeted skills being trained, social validity, effectiveness of the intervention, and whether generalization occurred. Key themes explored in the literature include the role of immersive experiences in enhancing learning outcomes when comparing VR training to BAU and the adaptability of VR platforms to different skill sets. Special attention was given to identifying factors that contribute to the success or limitation of VR-based training initiatives, including individual differences, technology acceptance, and effectiveness.

Objective: We used a framework to assess the value implications of thoracic surgeon operative volume within an 8-hospital health system. Methods: Surgical cases for non–small cell lung cancer were assessed from March 2015 to March 2021. High-volume (HV) surgeons performed >25 pulmonary resections annually. Metrics include length of stay, infection rates, 30-day readmission, in-hospital mortality, median 30-day charges and direct costs, and 3-year recurrence-free and overall survival. Multivariate regression-based propensity scores matched patients between groups. Metrics were graphed on radar charts to conceptualize total value. Results: All 638 lung resections were performed by 12 surgeons across 6 hospitals. Two HV surgeons performed 51% (n = 324) of operations, and 10 low-volume surgeons performed 49% (n = 314). Median follow-up was 28.8 months (14.0-42.3 months). Lobectomy was performed in 71% (n = 450) of cases. HV surgeons performed more segmentectomies (33% [n = 107] vs 3% [n = 8]; P

Abstract The type VI secretion system (T6SS) of Gram-negative bacteria inhibits competitor cells through contact-dependent translocation of toxic effector proteins. In Proteobacteria, the T6SS is anchored to the cell envelope through a megadalton-sized membrane complex (MC). However, the genomes of Bacteroidota with T6SSs appear to lack genes encoding homologs of canonical MC components. Here, we identify five genes in Bacteroides fragilis (tssNQOPR) that are essential for T6SS function and encode a Bacteroidota-specific MC. We purify this complex, reveal its dimensions using electron microscopy, and identify a protein-protein interaction network underlying the assembly of the MC including the stoichiometry of the five TssNQOPR components. Protein TssN mediates the connection between the Bacteroidota MC and the conserved baseplate. Although MC gene content and organization varies across the phylum Bacteroidota, no MC homologs are detected outside of T6SS loci, suggesting ancient co-option and functional convergence with the non-homologous MC of Pseudomonadota.

Adult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but it remains unknown how this circuit affects behavioral function. Here, we show that abGC input to the CA2 of adult mice is involved in the retrieval of remote developmental memories of the mother. Ablation of abGCs impaired the ability to discriminate between a caregiving mother and a novel mother, and this ability returned after abGCs were regenerated. Chemogenetic inhibition of projections from abGCs to the CA2 also temporarily prevented the retrieval of remote mother memories. These findings were observed when abGCs were inhibited at 4–6 weeks old, but not when they were inhibited at 10–12 weeks old. We also found that abGCs are necessary for differentiating features of CA2 network activity, including theta-gamma coupling and sharp wave ripples, in response to novel versus familiar social stimuli. Taken together, these findings suggest that abGCs are necessary for neuronal oscillations associated with discriminating between social stimuli, thus enabling retrieval of remote developmental memories of the mother by their adult offspring.

Abstract Aerosol‐cloud interactions (ACI) in warm clouds are the primary source of uncertainty in effective radiative forcing (ERF) during the historical period and, by extension, inferred climate sensitivity. The ERF due to ACI (ERFaci) is composed of the radiative forcing due to changes in cloud microphysics and cloud adjustments to microphysics. Here, we examine the processes that drive ERFaci using a perturbed parameter ensemble (PPE) hosted in CAM6. Observational constraints on the PPE result in substantial constraints in the response of cloud microphysics and macrophysics to anthropogenic aerosol, but only minimal constraint on ERFaci. Examination of cloud and radiation processes in the PPE reveal buffering of ERFaci by the interaction of precipitation efficiency and radiative susceptibility.

No abstract available.

One of the salient nuclear fuel performance parameters for new fuel types under development is changes in fuel thickness. To test the new commercially fabricated U-10Mo monolithic plate-type fuel, an irradiation experiment was designed that consisted of multiple mini-plate capsules distributed within the Advanced Test Reactor (ATR) core, the mini-plate 1 (MP-1) experiment. Each capsule contains eight mini-plates that were either fueled or “dummy” plates. Fuel thickness changes within a fuel assembly can be characterized by measuring the gaps between the plates ultrasonically. The channel gap probe (CGP) system is designed to measure the gaps between the plates and will provide information that supports qualification of U-10Mo monolithic fuel. This study will discuss the design and the results from the use of a custom-designed CGP system for characterizing the gaps between mini-plates within the MP-1 capsules. To ensure accurate and repeatable data, acceptance and calibration procedures have been developed. Unfortunately, there is no “gold” standard measurement to compare to CGP measurements. An effort was made to use plate thickness obtained from post-irradiation measurements to derive channel gap estimates for comparison with the CGP characterization.

Abstract Proximal spinal muscular atrophy (SMA) is a leading genetic cause for infant death in the world and results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of SMN protein and small molecules that can increase SMN expression are of considerable interest as potential therapeutics. Previous studies have shown that both 4-phenylbutyrate (4PBA) and trichostatin A (TSA) increase SMN expression in dermal fibroblasts derived from SMA patients. AR42 is a 4PBA-tethered TSA derivative that is a very potent histone deacetylase inhibitor. SMA patient fibroblasts were treated with either AR42, AR19 (a related analogue), 4PBA, TSA or vehicle for 5 days and then immunostained for SMN localization. AR42 as well as 4PBA and TSA increased the number of SMN-positive nuclear gems in a dose-dependent manner while AR19 did not show marked changes in gem numbers. While gem number was increased in AR42-treated SMA fibroblasts, there were no significant changes in FL-SMN mRNA or SMN protein. The neuroprotective effect of this compound was then assessed in SMNΔ7 SMA (SMN2 +/+ ;SMNΔ7 +/+ ;mSmn −/− ) mice. Oral administration of AR42 prior to disease onset increased the average lifespan of SMNΔ7 SMA mice by ~ 27% (20.1 ± 1.6 days for AR42-treated mice vs. 15.8 ± 0.4 days for vehicle-treated mice). AR42 treatment also improved motor function in these mice. AR42 treatment inhibited histone deacetylase (HDAC) activity in treated spinal cord although it did not affect SMN protein expression in these mice. AKT and GSK3β phosphorylation were both significantly increased in SMNΔ7 SMA mouse spinal cords. In conclusion, presymptomatic administration of the HDAC inhibitor AR42 ameliorates the disease phenotype in SMNΔ7 SMA mice in a SMN-independent manner possibly by increasing AKT neuroprotective signaling.

Abstract The pancreatic islet β-cell’s preference for release of newly synthesized insulin requires careful coordination of insulin exocytosis with sufficient insulin granule production to ensure that insulin stores exceed peripheral demands for glucose homeostasis. Thus, the cellular mechanisms regulating insulin granule production are critical to maintaining β-cell function. In this report, we utilized the synchronous protein trafficking system, RUSH, in primary β-cells to evaluate proinsulin transit through the secretory pathway leading to insulin granule formation. We demonstrate that the trafficking, processing, and secretion of the proinsulin RUSH reporter, proCpepRUSH, are consistent with current models of insulin maturation and release. Using both a rodent dietary and genetic model of hyperglycemia and β-cell dysfunction, we show that proinsulin trafficking is impeded at the Golgi and coincides with the decreased appearance of nascent insulin granules at the plasma membrane. Ultrastructural analysis of β-cells from diabetic leptin receptor deficient mice revealed gross morphological changes in Golgi structure, including shortened and swollen cisternae, and partial Golgi vesiculation, which are consistent with defects in secretory protein export. Collectively, this work highlights the utility of the proCpepRUSH reporter in studying proinsulin trafficking dynamics and suggests that altered Golgi export function contributes to β-cell secretory defects in the pathogenesis of Type 2 diabetes.

ABSTRACT Developing software tools that leverage biological data sets to accelerate drug discovery is an important aspect of bioinformatic research. Here, we present a novel example: a web application called Rocket-miR that applies an existing bioinformatic algorithm (IntaRNA) to predict cross-species miRNA-mRNA interactions and identify human miRNAs with potential antimicrobial activity against antibiotic-resistant bacterial infections. Rocket-miR is the logical extension of our prior finding that human miRNA let-7b-5p impairs the ability of the ubiquitous opportunistic pathogen Pseudomonas aeruginosa to form biofilms and resist the bactericidal effect of β-lactam antibiotics. Rocket-miR’s point and click interface enables researchers without programming expertise to predict additional human-miRNA-pathogen interactions. Identified miRNAs can be developed into novel antimicrobials effective against the 24 clinically relevant pathogens, implicated in diseases of the lung, gut, and other organs, that are included in the application. The paper incorporates three case studies contributed by microbiologists that study human pathogens to demonstrate the usefulness and usability of the application. Rocket-miR is accessible at the following link: http://scangeo.dartmouth.edu/RocketmiR/.IMPORTANCEAntimicrobial-resistant infections contribute to millions of deaths worldwide every year. In particular, the group of bacteria collectively known as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.) pathogens are of considerable medical concern due to their virulence and exceptional ability to develop antibiotic resistance. New kinds of antimicrobial therapies are urgently needed to treat patients for whom existing antibiotics are ineffective. The Rocket-miR application predicts targets of human miRNAs in bacterial and fungal pathogens, rapidly identifying candidate miRNA-based antimicrobials. The application’s target audience are microbiologists that have the laboratory resources to test the application’s predictions. The Rocket-miR application currently supports 24 recognized human pathogens that are relevant to numerous diseases including cystic fibrosis, chronic obstructive pulmonary disease (COPD), urinary tract infections, and pneumonia. Furthermore, the application code was designed to be easily extendible to other human pathogens that commonly cause hospital-acquired infections.

Sirtuin 6 (SIRT6) is a member of the mammalian sirtuin family of NAD+-dependent protein deacylases, homologues of the yeast silent information regulator 2 (Sir2). SIRT6 has remarkably diverse functions and plays a key role in a variety of biological processes for maintaining cellular and organismal homeostasis. In this review, our primary aim is to summarize recent progress in understanding SIRT6’s functions in the retina and retinal pigment epithelium (RPE), with the hope of further drawing interests in SIRT6 to increase efforts in exploring the therapeutic potential of this unique protein in the vision field. Before describing SIRT6’s role in the eye, we first discuss SIRT6’s general functions in a wide range of biological contexts. SIRT6 plays an important role in gene silencing, metabolism, DNA repair, antioxidant defense, inflammation, aging and longevity, early development, and stress response. In addition, recent studies have revealed SIRT6’s role in macrophage polarization and mitochondrial homeostasis. Despite being initially understudied in the context of the eye, recent efforts have begun to elucidate the critical functions of SIRT6 in the retina and RPE. In the retina, SIRT6 is essential for adult retinal function, regulates energy metabolism by suppressing glycolysis that affects photoreceptor cell survival, protects retinal ganglion cells from oxidative stress, and plays a role in Müller cells during early neurodegenerative events in diabetic retinopathy. In the RPE, SIRT6 activates autophagy in culture and protects against oxidative stress in mice. Taken together, this review demonstrates that better understanding of SIRT6’s functions and their mechanisms, both in and out of the context of the eye, holds great promise for the development of SIRT6-targeted strategies for prevention and treatment of blinding eye diseases.

Aggressive diagnostic testing remains an indispensable strategy for health and aged care facilities to prevent the transmission of SARS-CoV-2 in vulnerable populations. The preferred diagnostic platform has shifted towards COVID-19 rapid antigen tests (RATs) to identify the most infectious individuals. As such, RATs are being manufactured faster than at any other time in our history yet lack the relevant quantitative analytics required to inform on absolute analytical sensitivity enabling manufacturers to maintain high batch-to-batch reproducibility, and end-users to accurately compare brands for decision making. Here, we describe a novel reference standard to measure and compare the analytical sensitivity of RATs using a recombinant GFP-tagged nucleocapsid protein (NP-GFP). Importantly, we show that the GFP tag does not interfere with NP detection and provides several advantages affording streamlined protein expression and purification in high yields as well as faster, cheaper and more sensitive quality control measures for post-production assessment of protein solubility and stability. Ten commercial COVID-19 RATs were evaluated and ranked using NP-GFP as a reference standard. Analytical sensitivity data of the selected devices as determined with NP-GFP did not correlate with those reported by the manufacturers using the median tissue culture infectious dose (TCID50) assay. Of note, TCID50 discordance has been previously reported. Taken together, our results highlight an urgent need for a reliable reference standard for evaluation and benchmarking of the analytical sensitivity of RAT devices. NP-GFP is a promising candidate as a reference standard that will ensure that RAT performance is accurately communicated to healthcare providers and the public.

Background: Stuttering support groups (SSGs) have been a long-standing invaluable resource for people who stutter (PWS) but research into SSGs is only emerging. Speech-language therapists (SLTs) need further insight to successfully facilitate SSGs. Objectives: To determine PWS’ perspectives regarding why they attend SSGs in South Africa. Method: Thirteen PWS who attend SSGs, between 20 and 58 years old, were a part of this qualitative study. Purposive sampling was utilised. Semi-structured telephonic interviews were used and data was analysed thematically. Results: Four themes, namely, ‘altered perceptions’, ‘increased sense of community’, ‘support group reciprocity’, and ‘support group environment, participants and topics’, were identified. The results yielded clinical implications which included SLTs encouraging: (1) improved perceptions of being a PWS through education and self-empowerment, (2) PWS’ connections between meetings to increase the sense of community, (3) reciprocity in meetings, (4) sharing personal stories to promote learning and general self-management and (5) support, praise and education to empower and encourage PWS. This study’s findings show that SSGs helped PWS accept their stutter and gain confidence. This study showcased how SSGs can help PWS manage their fluency and gain confidence. Additionally, this study supports current research which suggests that dysfluency and social-emotional well-being should be equally addressed. Conclusion: Recommendations were generated from PWS’ perspectives and included focusing discussions on fluency, emotions and sharing personal stories. Insights from PWS helped better inform SLTs of their role within SSGs including guiding and facilitating conversations. Contribution: People who stutters’ perspectives can be used in clinical practice to help SLTs meet the needs of PWS and guide best practice when facilitating SSGs.

The identification of persistent radio sources (PRSs) coincident with two repeating fast radio bursts (FRBs) supports FRB theories requiring a compact central engine. However, deep nondetections in other cases highlight the diversity of repeating FRBs and their local environments. Here, we perform a systematic search for radio sources towards 37 CHIME/FRB repeaters using their arcminute localizations and a combination of archival surveys and targeted observations. Through multiwavelength analysis of individual radio sources, we identify two (20181030A-S1 and 20190417A-S1) for which we disfavor an origin of either star formation or an active galactic nucleus in their host galaxies and thus consider them candidate PRSs. We do not find any associated PRSs for the majority of the repeating FRBs in our sample. For eight FRB fields with Very Large Array imaging, we provide deep limits on the presence of PRSs that are 2–4 orders of magnitude fainter than the PRS associated with FRB 20121102A. Using Very Large Array Sky Survey imaging of all 37 fields, we constrain the rate of luminous (≳10 ^40 erg s ^−1 ) PRSs associated with repeating FRBs to be low. Within the context of FRB-PRS models, we find that 20181030A-S1 and 20190417A-S1 can be reasonably explained within the context of magnetar, hypernebulae, gamma-ray burst afterglow, or supernova ejecta models—although we note that both sources follow the radio luminosity versus rotation measure relationship predicted in the nebula model framework. Future observations will be required to both further characterize and confirm the association of these PRS candidates with the FRBs.

Detecting fast radio bursts (FRBs) with frequency-dependent intensity remains a challenge, as existing search algorithms do not account for the spectral shape, potentially leading to nondetections. We propose a novel detection statistic, which we call the Kalman detector, that improves the sensitivity of FRB signal detection by incorporating spectral shape information. The detection statistic is based on an optimal matched filter, marginalizing over all possible intensity functions, weighted by a random walk probability distribution, considering some decorrelation bandwidth. Our analysis of previously detected FRBs demonstrates that the Kalman score provides a comparable yet independent source of information for bursts with significant spectral structure, and the sensitivity improvement is of the order 0%–200% with a median improvement of 20%. We also applied the Kalman detector to existing data from FRB 20201124A and detected two new repeat bursts that were previously missed. Furthermore, we suggest a practical implementation for real-time surveys by employing a low significance soft-trigger from initial flux integration-based detection algorithms. The Kalman detector has the potential to significantly enhance FRB detection capabilities and enable new insights into the spectral properties of these enigmatic astrophysical phenomena.

Fast radio bursts (FRBs) are a powerful and mysterious new class of transients that are luminous enough to be detected at cosmological distances. By associating FRBs to host galaxies, we can measure intrinsic and environmental properties that test FRB origin models, in addition to using them as precise probes of distant cosmic gas. The Deep Synoptic Array (DSA-110) is a radio interferometer built to maximize the rate at which it can simultaneously detect and localize FRBs. Here, we present the first sample of FRBs and host galaxies discovered by the DSA-110. This sample of 11 FRBs is the largest, most uniform sample of localized FRBs to date, as it is selected based on association with host galaxies identified in optical imaging by Pan-STARRS1. These FRBs have not been observed to repeat, and their radio properties (dispersion, temporal scattering, energy) are similar to that of the known nonrepeating FRB population. Most host galaxies have ongoing star formation, as has been identified before for FRB hosts. Two hosts of the new sample are massive, quiescent galaxies. The distribution of star formation history across this host-galaxy sample shows that the delay time distribution is wide, with a power-law model that spans from ∼100 Myr to ≳2 Gyr. This requires the existence of one or more progenitor formation channels associated with old stellar populations, such as the binary evolution of compact objects.

We report on the detection of radio bursts from the Galactic bulge using the real-time transient detection and localization system, realfast . The pulses were detected commensally on the Karl G. Jansky Very Large Array during a survey of unidentified Fermi γ -ray sources. The bursts were localized to subarcsecond precision using realfast fast-sampled imaging. Follow-up observations with the Green Bank Telescope detected additional bursts from the same source. The bursts do not exhibit periodicity in a search up to periods of 480 s, assuming a duty cycle of

While robotics have been widely used in many agricultural practices such as harvesting, seeding, cattle monitoring, etc., aquaculture farming is an important, fast-growing sector of agriculture that has not seen significant adoption of advanced technologies such as robotics and the Internet of Things (IoT). In particular, dissolved oxygen (DO) monitoring, a practice in pond aquaculture essential to the health of the fish crops, remains labor-intensive and time-consuming. The Hybrid Aerial Underwater robotiCs System (HAUCS) is an IoT framework that aims to bring transformative changes to pond aquaculture. This paper focuses on the latest development in the HAUCS mobile sensing platform and field deployment. To address some shortcomings with the current implementation, the development of a novel rigid Kirigami-based robotic extension subsystem that can expand the functionality of the HAUCS platform is also being discussed.

Chromatin is dynamically reorganized spatially and temporally, and the post-translational modification of histones is a key component of this regulation. The basic subunit of chromatin is the nucleosome core particle, consisting of two copies each of the histones H2A, H2B, H3, and H4 around which ∼147 base pairs of DNA wrap. The intrinsically disordered histone termini, or tails, protrude from the core and are heavily post-translationally modified. Previous studies have shown that the histone tails exist in dynamic ensembles of DNA-bound states within the nucleosome. Histone tail interactions with DNA are involved in nucleosome conformation and chromatin organization. Charge-modulating histone post-translational modifications (PTMs) are poised to perturb the dynamic interactions between histone tails and DNA. Arginine side chains form favorable interactions with DNA and are sites of charge-modulating PTMs such as citrullination. Our current focus is on the H3 tail, the longest histone tail. Four arginine residues are relatively evenly spaced along the H3 tail sequence, suggesting multivalent interactions with DNA poised for regulation by PTMs. In this study, we use NMR nuclear spin relaxation experiments to investigate the contribution of arginine residues to H3 tail dynamics within the nucleosome core particle. By neutralizing arginine via mutation to glutamine, we begin to work towards a comprehensive understanding of the contribution of individual residues to H3 tail dynamics. We find that neutralization of arginine residues results in increased regional mobility of the H3 tails, with implications for understanding the direct effects of arginine citrullination. Altogether, these studies support a role for dynamics within the histone language and emphasize the importance of charge-modulating histone PTMs in regulating chromatin dynamics, starting at the level of the basic subunit of chromatin.

Abstract Background Autistic individuals frequently experience social communication challenges. Girls are diagnosed with autism less often than boys even when their symptoms are equally severe, which may be due to insufficient understanding of the way autism manifests in girls. Differences in the behavioral presentation of autism, including how people talk about social topics, could contribute to these persistent problems with identification. Despite a growing body of research suggesting that autistic girls and boys present distinct symptom profiles in a variety of domains, including social attention, friendships, social motivation, and language, differences in the way that autistic boys and girls communicate verbally are not yet well understood. Closely analyzing boys’ and girls’ socially-focused language during semi-structured clinical assessments could shed light on potential sex differences in the behavioral presentation of autistic individuals that may prove useful for identifying and effectively supporting autistic girls. Here, we compare social word use in verbally fluent autistic girls and boys during the interview sections of the ADOS-2 Module 3 and measure associations with clinical phenotype. Methods School-aged girls and boys with autism (N = 101, 25 females; aged 6–15) were matched on age, IQ, and parent/clinician ratings of autism symptom severity. Our primary analysis compared the number of social words produced by autistic boys and girls (normalized to account for differences in total word production). Social words are words that make reference to other people, including friends and family. Results There was a significant main effect of sex on social word production, such that autistic girls used more social words than autistic boys. To identify the specific types of words driving this effect, additional subcategories of friend and family words were analyzed. There was a significant effect of sex on friend words, with girls using significantly more friend words than boys. However, there was no significant main effect of sex on family words, suggesting that sex differences in social word production may be driven by girls talking more about friends compared to boys, not family. To assess relationships between word use and clinical phenotype, we modeled ADOS-2 Social Affect (SA) scores as a function of social word production. In the overall sample, social word use correlated significantly with ADOS-2 SA scores, indicating that participants who used more social words were rated as less socially impaired by clinicians. However, when examined in each sex separately, this result only held for boys. Limitations This study cannot speak to the ways in which social word use may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. Conclusions Autistic girls used significantly more social words than boys during a diagnostic assessment—despite being matched on age, IQ, and both parent- and clinician-rated autism symptom severity. Sex differences in linguistic markers of social phenotype in autism are especially important in light of the late or missed diagnoses that disproportionately affect autistic girls. Specifically, heightened talk about social topics could complicate autism referral and diagnosis when non-clinician observers expect a male-typical pattern of reduced social focus, which autistic girls may not always exhibit.

Abstract Background Prior studies have assessed provider knowledge and factors associated with opioid misuse; similar studies evaluating patient knowledge are lacking. The purpose of this study was to assess the degree of understanding regarding opioid use in orthopaedic trauma patients. We also sought to determine the demographic factors and clinical and personal experiences associated with level of understanding. Methods One hundred and sixty-six adult orthopaedic trauma surgery patients across two clinical sites of an academic institution participated in an internet-based survey (2352 invited, 7.1% response rate). Demographic, clinical, and personal experience variables, as well as perceptions surrounding opioid use were collected. Relationships between patient characteristics and opioid perceptions were identified using univariate and multivariable logistic regressions. Alpha = 0.05. Results Excellent recognition (> 85% correct) of common opioids, side effects, withdrawal symptoms, and disposal methods was demonstrated by 29%, 10%, 30%, and 2.4% of patients; poor recognition (

Abstract A modified Chromium 10x droplet-based protocol that subsamples cells for both short-read and long-read (nanopore) sequencing together with a new computational pipeline (FLAMES) is developed to enable isoform discovery, splicing analysis, and mutation detection in single cells. We identify thousands of unannotated isoforms and find conserved functional modules that are enriched for alternative transcript usage in different cell types and species, including ribosome biogenesis and mRNA splicing. Analysis at the transcript level allows data integration with scATAC-seq on individual promoters, improved correlation with protein expression data, and linked mutations known to confer drug resistance to transcriptome heterogeneity.

miR-126 is highly expressed in inv(16) Acute myeloid leukemia (AML) but its role is unclear. Here, the authors show that the aberrant expression of miR-126 in inv(16) AML is directly due to the CBFB-MYH11 fusion gene and that it can promote AML development and leukemia stem cell maintenance, highlighting miR-126 as a therapeutic target for inv(16) AML patients

Category: Sports; Basic Sciences/Biologics Introduction/Purpose: Achilles tendon ruptures have increased 10-fold in the past three decades, leading to long-term functional deficits in nearly two-thirds of patients. To counter this, rehabilitation protocols have been developed to strike a balance between protecting the healing tendon from re-rupture while allowing patients to return to activities of daily living as early as possible. However, Achilles tendon loading is neither prescribed nor quantified during immobilization and there is no standardized method of immobilization. Therefore, the purpose of this study was to quantify the amount of tendon loading experienced while walking in 3 different kinds immobilizing boot with respect to prescribed ankle angle and walking speed. Methods: Two healthy-young adults (2M; Age: 29.6 +- 2.3 y/o; BMI: 30 +- 7) walked over flat ground while wearing 3 different immobilizing boots and athletic shoes after providing written informed consent in this IRB approved study. We calculated Achilles tendon loading while subjects walked in 3 boots that positioned the ankle in 30 degrees of plantar flexion (Figure A, Air Cam Walker, United Ortho; AirSelect Walker, Aircast, VACOped, OPED). In all three boots, an instrumented insole (Loadsol, Novel) was placed under the foot to quantify load experienced by the tendon. We calculated the Achilles tendon loading profiles during gait for each immobilizing boot and compared them against the normal shod condition. We also provided the surgical repair threshold of 0.5 bodyweights to visualize the potential efficacy of each immobilizing boot for early rehabilitation when the tendon is early in the healing phase. Results: As expected, tendon loading was highest in the shod condition with no ankle bracing and lowest in the fully plantarflexed adjustable boot (Figure B). On average, the immobilizing boots reduced tendon loading decreased by 68% compared to unsupported walking in shoes but there were differences among the boots. The 3 different immobilizing boots provided differing levels of support. The 2 walking boots that use heel wedges to support the ankle in plantar flexion provided the least support, reducing loading by an average of 60-68%. The more rigid boot that constrained ankle angle using a posterior strut reduced tendon loading by 77% compared to gait in a normal walking shoe. Based on biomechanical studies of Achilles tendon repair strength in cadaveric experiments, only the rigid boot with the posterior strut reduced tendon loading biomechanics to levels that could be resisted by the surgical repair (Figure B). Conclusion: In this study, we used an instrumented insole to quantify Achilles tendon loading in a variety of immobilizing boots used by rupture patients. Our initial findings show that tendon loading is varies greatly between boot types and patients, highlighting the importance of understanding how these loads change in patients. Our future work centers around identifying the tendon loading profiles that promote tendon healing and optimize patient outcomes. These loading profiles will then provide the quantitative data needed to personalize loading for patients and guide rehabilitation to improve outcomes.

Category: Ankle Arthritis; Ankle Introduction/Purpose: Choosing a treatment course can be challenging for patients with ankle osteoarthritis given the multiple operative and nonoperative options. We developed and validated the Ankle Arthritis Patient Decision Aid as a tool to improve shared decision-making for such patients. Methods: Eighty patients of 2 surgeons at a US academic foot and ankle practice were recruited from October 2020 to June 2021 using an electronic medical record messaging system. Participants reviewed the tool and answered survey questions evaluating its quality and factors affecting treatment choice in a hypothetical patient scenario. We evaluated the tool using decisional conflict scores (maximum, 40 points, with higher scores indicating greater uncertainty), pre- and post-knowledge test scores (maximum, 8 points), and helpfulness scores (maximum, 7 points). We compared pre- and post-test knowledge scores using paired Student t- tests. Alpha=.05. Results: Mean (+- standard deviation) knowledge scores improved from 4.8 +- 1.2 (pre-test) to 6.7 +- 1.3 (post-test), for a mean improvement of 1.9 +- 1.4 (p

Background: Severe acute malnutrition (SAM) is associated with cognitive and motor deficits. Little is known about the swallowing, feeding and communication characteristics of hospitalised toddlers with SAM, limiting the abilities of speech-language therapists to provide effective early intervention. Objective: To explore the background, swallowing, feeding and communication characteristics of toddlers with SAM during in-patient nutritional rehabilitation. Method: An exploratory, prospective, collective case-study was conducted with three hospitalised toddlers who were 12–18 months old and independently diagnosed with SAM, at least 1 week after transitioning to oral feeding. Detailed case histories were compiled through medical file perusal and parent interviews. Cross-sectional clinical bedside assessments were completed with the Rossetti Infant-Toddler Language Scale and Schedule for Oral-Motor Assessment. Results: All three participants had a history of feeding difficulties before admission. Despite intact pharyngeal swallows, heterogeneous oral-sensorimotor dysfunction and disruptive feeding behaviours were identified. Risk for oropharyngeal dysphagia indicates the need to modify dietary consistencies to prevent prolonging recovery or SAM relapse. Participants had mild-to-moderate language delays, particularly in interaction-attachment, play and language comprehension, with an atypical moderate receptive and mild expressive language delay profile. None of the participants were referred for speech-language therapy. Conclusion: This exploratory research showed the oral-sensorimotor skills, swallowing and communication characteristics of children with SAM. Speech-language therapists could address oral-sensorimotor functioning, feeding difficulties and communication interaction delays before discharge to community-based management for SAM. Further investigation with a larger sample size is recommended. Contribution: Novel description of the oral-sensorimotor skills for feeding and the communication development of three severely malnourished toddlers with HIV and tuberculosis co-infection was presented. The complexity of the three cases is highlighted.

Abstract The role of calcium in blood pressure has been widely studied among hypertensive patients; however, no study has explored the role of calcium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum calcium levels between hypertensive crises patients and a 1:1 random matched controls (age‐, sex‐, race‐, diabetes, and body mass index matched). This study is a single‐center, retrospective, chart review, case‐control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented calcium level. The control group patients were required to be 18 years of age or older, have a documented calcium level, and have no diagnosis of hypertensive crises. The primary outcome of the study was to compare the mean serum calcium in patients with hypertensive crises vs patients without hypertensive crises. Five hundred and sixty‐six patients were included in the study: 283 patients in both the case group and control group. The primary outcome results showed that serum calcium concentration was not significantly different between the case group (8.99 ± 0.78 mg/dL) and control group (8.96 ± 0.75 mg/dL) (P = .606). This study found no significant difference in serum calcium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of calcium on blood pressure in hypertensive crises.

Abstract Although the role of magnesium in blood pressure has been well studied among hypertensive patients, no study has explored the role of magnesium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum magnesium levels between hypertensive crises patients and matched controls (age‐, sex‐, race‐, and diabetes‐matched) in a 1:1 random match. This study is a single‐center, retrospective, chart review, case‐control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented magnesium level. The control group patients were required to be 18 years of age or older, have no diagnosis of hypertensive crises, and have a documented magnesium level. The primary outcome of the study was to compare the mean serum magnesium in patients with hypertensive crises versus patients without hypertensive crises. Three hundred and fifty‐eight patients were included in the study: 179 patients in both the case group and control group. The primary outcome results showed that serum magnesium concentration was not significantly different between the case group (1.89 ± 0.29 mg/dl) and control group (1.90 ± 0.31 mg/dl) (p = .787). This study found no significant difference in serum magnesium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of magnesium on blood pressure in hypertensive crises.

Summary: Background: Though case fatality rate (CFR) is widely used to reflect COVID-19 fatality risk, its use is limited by large temporal and spatial variation. Hospital mortality rate (HMR) is also used to assess the severity of COVID-19, but HMR data is not directly available globally. Alternative metrics are needed for COVID-19 severity and fatality assessment. Methods: We introduce new metrics for COVID-19 fatality risk measurements/monitoring and a new mathematical model to estimate average hospital length of stay for deaths (Ldead) and discharges (Ldis). Multiple data sources were used for our analyses. Findings: We propose three, new metrics: hospital occupancy mortality rate (HOMR), ratio of total deaths to hospital occupancy (TDHOR), and ratio of hospital occupancy to cases (HOCR), for dynamic assessment of COVID-19 fatality risk. Estimated Ldead and Ldis for 501,079 COVID-19 hospitalizations in 34 US states between 7 August 2020 and 1 March 2021 were 18·2(95%CI:17·9-18·5) and 14·0(95%CI:13·9-14·0) days, respectively. We found the dramatic changes in COVID-19 CFR observed in 27 countries during early stages of the pandemic were mostly caused by undiagnosed cases. Compared to the first week of November 2021, the week mean HOCRs (mimics hospitalization-to-case ratio) for Omicron variant (58·6% of US new cases as of 25 December 2021) decreased 65·16% in the US as of 16 January 2022. Interpretation: The new and reliable measurements described here could be useful for COVID-19 fatality risk and variant-associated risk monitoring. Funding: No specific funding was associated with the present study.

The ex-copula penile dorsiflexion reflex (PDFR) is an established measure of sexual dysfunction in male rat models of spinal cord injury. Although the PDFR after complete spinal transection is well described, information regarding the more clinically relevant incomplete spinal contusion injury model is limited. This study examined, using two-dimensional (2D) kinematic analysis, the relationship between the PDFR and degree of white matter sparing (WMS). Male Wistar rats received a T9 contusion with varying degrees of impactor forces. Weekly kinematic recordings of the PDFR were made 3–8 weeks postinjury. Sexual reflex components examined included maximum angle of penile dorsiflexion, total penile event duration, and penile ascent speed. Post hoc comparison between animals grouped based upon injury severity (moderate–severe: 13.33%–17.15% WMS vs moderate: 20.85%–33.50% WMS) indicated PDFR effects. Specifically, the numbers of animals with more moderate contusions having data points above the median in both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe injuries. Total penile event duration was also affected but only at more chronic time points (6–8 weeks). Thus, 2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.

Abstract Background Individuals with autism spectrum disorder (ASD) are characterized by social communication challenges and repetitive behaviors that may be quickly detected by experts (Autism Res 10:653–62, 2017; American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2013). Recent research suggests that even naïve non-experts judge a variety of human dimensions using narrow windows of experience called “first impressions.” Growing recognition of sex differences in a variety of observable behaviors in ASD, combined with research showing that some autistic girls and women may “camouflage” outward symptoms, suggests it may be more difficult for naïve conversation partners to detect ASD symptoms in girls. Here, we explore the first impressions made by boys and girls with ASD and typically developing (TD) peers. Methods Ninety-three school-aged children with ASD or TD were matched on IQ; autistic girls and boys were additionally matched on autism symptom severity using the ADOS-2. Participants completed a 5-minute “get-to-know-you” conversation with a new young adult acquaintance. Immediately after the conversation, confederates rated participants on a variety of dimensions. Our primary analysis compared conversation ratings between groups (ASD boys, ASD girls, TD boys, TD girls). Results Autistic girls were rated more positively than autistic boys by novel conversation partners (better perceived social communication ability), despite comparable autism symptom severity as rated by expert clinicians (equivalent true social communication ability). Boys with ASD were rated more negatively than typical boys and typical girls by novel conversation partners as well as expert clinicians. There was no significant difference in the first impressions made by autistic girls compared to typical girls during conversations with a novel conversation partner, but autistic girls were rated lower than typical girls by expert clinicians. Limitations This study cannot speak to the ways in which first impressions may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. Conclusions First impressions made during naturalistic conversations with non-expert conversation partners could—in combination with clinical ratings and parent report—shed light on the nature and effects of behavioral differences between girls and boys on the autism spectrum.

Abstract The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There were insufficient data to compare across treatments. Many treatments have been administered to the first 9152 reported cases of COVID-19. These data serve as the basis for an open-source registry of all reported treatments given to COVID-19 patients at www.CDCN.org/CORONA . Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols.

Background. Parathyroid allotransplantation is a burgeoning treatment for severe hypoparathyroidism. Deceased donor parathyroid gland (PTG) procurement can be technically challenging due to lack of normal intraoperative landmarks and exposure constraints in the neck of organ donors. In this study, we assessed standard 4-gland exposure in situ and en bloc surgical techniques for PTG procurement and ex vivo near-infrared autofluorescence (NIRAF) imaging for identification of PTGs during organ recovery. Methods. Research tissue consent was obtained from organ donors or donor families for PTG procurement. All donors were normocalcemic, brain-dead, solid organ donors between 18 and 65 y of age. PTGs were procured initially using a standard 4-gland exposure technique in situ and subsequently using a novel en bloc resection technique after systemic organ preservation flushing. Parathyroid tissue was stored at 4 °C in the University of Wisconsin solution up to 48 h post-procurement. Fluoptics Fluobeam NIRAF camera and Image J software were utilized for quantification of NIRAF signal. Results. Thirty-one brain-dead deceased donor PTG procurements were performed by abdominal transplant surgeons. In the initial 8 deceased donors, a mean of 1.75 glands (±1.48 glands SD) per donor were recovered using the 4-gland in situ technique. Implementation of combined en bloc resection with ex vivo NIRAF imaging in 23 consecutive donors yielded a mean of 3.60 glands (±0.4 SD) recovered per donor (P < 0.0001). Quantification of NIRAF integrated density signal demonstrated >1-fold log difference in PTG (2.13 × 105 pixels) versus surrounding anterior neck structures (1.9 × 104 pixels; P < 0.0001). PTGs maintain distinct NIRAF signal from the time of recovery (1.88 × 105 pixels) up to 48 h post-procurement (1.55 × 105 pixels) in organ preservation cold storage (P = 0.34). Conclusions. The use of an en bloc surgical technique with ex vivo NIRAF imaging significantly enhances the identification and recovery of PTG from deceased donors.

Abstract The whale shark Rhincodon typus is found throughout the world's tropical and warm‐temperate ocean basins. Despite their broad physical distribution, research on the species has been concentrated at a few aggregation sites. Comparing DNA sequences from sharks at different sites can provide a demographically neutral understanding of the whale shark's global ecology. Here, we created genetic profiles for 84 whale sharks from the Saudi Arabian Red Sea and 72 individuals from the coast of Tanzania using a combination of microsatellite and mitochondrial sequences. These two sites, separated by approximately 4500 km (shortest over‐water distance), exhibit markedly different population demographics and behavioral ecologies. Eleven microsatellite DNA markers revealed that the two aggregation sites have similar levels of allelic richness and appear to be derived from the same source population. We sequenced the mitochondrial control region to produce multiple global haplotype networks (based on different alignment methodologies) that were broadly similar to each other in terms of population structure but suggested different demographic histories. Data from both microsatellite and mitochondrial markers demonstrated the stability of genetic diversity within the Saudi Arabian aggregation site throughout the sampling period. These results contrast previously measured declines in diversity at Ningaloo Reef, Western Australia. Mapping the geographic distribution of whale shark lineages provides insight into the species’ connectivity and can be used to direct management efforts at both local and global scales. Similarly, understanding historical fluctuations in whale shark abundance provides a baseline by which to assess current trends. Continued development of new sequencing methods and the incorporation of genomic data could lead to considerable advances in the scientific understanding of whale shark population ecology and corresponding improvements to conservation policy.

Abstract Background Staging laparoscopy and peritoneal cytology can detect occult metastatic disease prior to treatment of gastric cancer. The yield of peritoneal staging in patients with early stage disease is lacking. We assess the yield of peritoneal staging in early stage gastric cancer and its impact on survival. Methods Data were obtained from a prospective database of patients who underwent staging laparoscopy and peritoneal cytology for gastric cancer at our institution between July 1995 and July 2018. Clinical stage was determined by endoscopic ultrasound, and early stage was defined as cT1-2 and cN0. Rates of positive cytology and carcinomatosis at time of laparoscopy were obtained. Univariate analyses were used to compare groups, and Kaplan-Meier survival analyses were used to assess survival outcomes. Results Eight hundred sixty-seven patients underwent staging laparoscopy and peritoneal cytology; 56 were defined as early stage. Age was 61 ± 12 years, 66.4% were male, and 62.3% were white. Of the patients with early stage disease, 17.9% had either gross carcinomatosis (10.7%) and/or positive peritoneal cytology (10.9%). All cases of peritoneal disease were in patients with cT2 disease. There were no differences in age, gender, or race based on peritoneal disease (all p > 0.05). The presence of carcinomatosis or positive cytology significantly affected overall survival (p < 0.001), regardless of clinical T or N stage. Conclusions Peritoneal staging identifies metastatic disease in a significant number of patients with early stage disease. Given its poor prognosis and alternate therapy options, independent staging laparoscopy and peritoneal cytology should be considered in patients with early stage gastric adenocarcinoma.

Understanding and anticipating the effects of climate change on fisheries social-ecological systems (FSESs) is central to proactive fisheries management in a changing global climate. With fisheries management increasingly striving to consider interactions and feedbacks among people, targeted species, and the broader ecological and human communities, fisheries managers and participants need tools to help them assess these complex systems. We developed a new climate vulnerability assessment framework for analyzing the impacts of a climate-induced trend or event on a FSES. The framework divides the FSES into four interrelated and interacting domains: Ecological Community, Fished Species, Fishery, and Human Community. The framework provides a systematic approach to account for indirect as well as direct effects, links among subsystems, and multiple climate change-induced stressors. We demonstrate the framework’s utility by applying it to three case studies: the effects of a marine heatwave on the Dungeness crab FSES, the effects of a marine heatwave on the red sea urchin FSES, and the effects of long-term climate trends on North Pacific albacore. We found that the effects of a climatic trend or event on a FSES are often indirect and can trigger diverse and important feedbacks. These examples also showed that the climatic trend or event may cause changes in the temporal and spatial distribution of fishing effort and fished species that have a more significant impact on the FSES than changes to species abundance per se. Unlike other climate vulnerability assessment frameworks and applications, ours is designed to enable consideration of the range of feedbacks within and among both the ecological and human communities. As such, it is a valuable tool to guide the holistic examination and assessment of potential impacts to FSESs.