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Abstract Estuaries are a globally important source of methane, but little is known about Australia’s contributions to global estuarine methane emissions. Here we present a first-order Australia-wide assessment of estuarine methane emissions, using methane concentrations from 47 estuaries scaled to 971 Australian estuaries based on geomorphic estuary types and disturbance classes. We estimate total mean (±standard error) estuary annual methane emissions for Australia of 30.56 ± 12.43 Gg CH4 yr−1. Estuarine geomorphology and disturbance interacted to control annual methane emissions through differences in water–air methane flux rates and surface area. Most of Australia’s estuarine surface area (89.8%) has water–air methane fluxes lower than global means, contributing 80.3% of Australia’s total mean annual estuarine methane emissions. Australia is a good analogue for the ~34% of global coastal regions classified as less than moderately disturbed (>40% intact), suggesting that these regions may also have lower methane fluxes. On this basis, recent global estuarine methane emission estimates that do not consider disturbance in their upscaling, probably overestimate global estuarine methane emissions.

ObjectivesWe present an adolescent in whom olfactory neuroblastoma (ONB) was detected on follow-up magnetic resonance imaging (MRI) 2.5 years after SIADH diagnosis. Our case contrasts prior pediatric reports in which ONB and SIADH were diagnosed concurrently.Case presentationA previously healthy 13-year-old girl was found to have SIADH during evaluation for restrictive eating. Work-up ruled out adrenal, thyroid and paraneoplastic causes, diuretic use, and vasopressin receptor and aquaporin channel mutations. Brain MRI was normal except for paranasal sinus (PNS) inflammatory changes to the left fronto-maxillary sinuses and frontoethmoidal recess. The sodium levels normalized with fluid restriction (800-900 ml/m2/day). Multiple repeated attempts to liberalize fluid intake resulted in recurrent hyponatremia. Follow-up brain MRIs 4 and 11 months after the initial presentation showed persistent PNS inflammatory changes. A subsequent brain MRI 31 months after initial presentation demonstrated a lesion in the left frontoethmoidal recess extending into the left nasal cavity and biopsy showed low grade ONB. The patient underwent surgery with normalization of serum sodium on liberalized fluid intake. Seven days after surgery, she had recurrence of SIADH, and brain MRI showed remnant of the ONB at the fovea ethmoidalis. She completed adjuvant radiotherapy though her SIADH persisted.ConclusionsOur case highlights the importance of considering ONB in the evaluation of children with SIADH. Idiopathic SIADH is rare in children and if no cause is identified, computed tomography of sinuses and nasal endoscopy should be considered earlier in the work-up of these patients, particularly in the absence of sinus symptoms.

California is the nation’s primary producer of almonds, pistachios, and walnuts, and an important producer of rice. Because of California’s diverse cropping systems, off-target herbicide drift can be a considerable problem, particularly from aerial applications that are commonly used in flooded rice production systems. Triclopyr is an auxin-mimic type herbicide that has been commonly used in rice for many years for control of broadleaf weeds and the industry is familiar with symptoms of off-target triclopyr drift. Florpyrauxifen-benzyl is a newly registered auxin-mimic herbicide in California rice with activity on key weeds and is being rapidly adopted. Although symptoms typically are similar among auxinic herbicides, it is important to understand subtle differences and risks among these herbicides as stewardship for newly registered products. This research was conducted in 2020 and 2021 to determine the relative sensitivity of almond, pistachio, and walnut trees to simulated drift rates of florpyrauxifen-benzyl and triclopyr as well as characterize and compare symptoms caused by these two herbicides. The fractional herbicide rates tested were 1/200X, 1/100X, 1/33X, and 1/10X of the florpyrauxifen-benzyl use rate of 29.4 g·ha−1 a.i. and 1/200X, 1/100X, and 1/33X of the triclopyr use rate of 420.3 g·ha−1 a.e. Florpyrauxifen-benzyl and triclopyr herbicides were applied directly to one side of the canopy of 1- to 2-year-old almond, pistachio, and walnut trees. The general symptoms of florpyrauxifen-benzyl and triclopyr were chlorosis, chlorotic spots, leaf curling, leaf narrowing, leaf distortion, leaf malformation, leaf crinkling, shoot curling, stem coloring, stunting, terminal bud death, and twisting. The florpyrauxifen-benzyl and triclopyr injury symptoms were compared at the same fractional rates and found to be similar to each other. The herbicide injury was observed on the entire pistachio canopy, particularly on developing leaves and terminal buds. In contrast, injury symptoms on almond and walnut were more apparent on the side of the canopy to which the herbicides were applied. Symptom severity peaked at 14 days after treatment with the 1/10X florpyrauxifen-benzyl rate, when the visible injury was 16%, 48%, and 78% on almond, walnut, and pistachio, respectively. Although almond and walnut symptoms from the 1/10X florpyrauxifen-benzyl rate remained visible longer than all other treatments, all trees gradually recovered throughout the growing season. In contrast, pistachio trees did not recover fully and had injury symptoms that persisted for the remainder of the treatment year and at leaf-out the following spring. When drift occurs, it is typically at rates below 1/100X up to 1/33X of herbicide use rates. This research suggested that proper herbicide drift management practices and application precautions are likely to minimize the risk of significant injury from florpyrauxifen-benzyl drift to almond and walnut because of low injury symptoms at the typical drift rates. However, extra precautions may be needed if there are nearby pistachio orchards.

Abstract Estuaries play an important role in connecting the global carbon cycle across the land-to-ocean continuum, but little is known about Australia’s contribution to global CO2 emissions. Here we present an Australia-wide assessment, based on CO2 concentrations for 47 estuaries upscaled to 971 assessed Australian estuaries. We estimate total mean (±SE) estuary CO2 emissions of 8.67 ± 0.54 Tg CO2-C yr−1, with tidal systems, lagoons, and small deltas contributing 94.4%, 3.1%, and 2.5%, respectively. Although higher disturbance increased water-air CO2 fluxes, its effect on total Australian estuarine CO2 emissions was small due to the large surface areas of low and moderately disturbed tidal systems. Mean water-air CO2 fluxes from Australian small deltas and tidal systems were higher than from global estuaries because of the dominance of macrotidal subtropical and tropical systems in Australia, which have higher emissions due to lateral inputs. We suggest that global estuarine CO2 emissions should be upscaled based on geomorphology, but should also consider land-use disturbance, and climate.

Pyroxasulfone is a very long chain fatty acid (VLCFA) inhibitor (group 15) with potential for preemergence weed control in orchard crops and would be beneficial for reducing selection pressure for resistance to more commonly used herbicides, such as glyphosate. Pyroxasulfone is registered and widely used in corn and soybeans in the United States as a solo product and in several premix formulations. However, there is limited published information on the performance and safety of pyroxasulfone in tree nut orchard systems. To assess the potential fit for pyroxasulfone in this crop sector, a series of crop safety and weed control efficacy experiments were carried out in key California orchard crops and in fallow fields with common orchard weeds. The non-crop studies were conducted near Davis, CA, to evaluate winter annual weed control with pyroxasulfone in comparison with pendimethalin and indaziflam. In addition, an irrigation incorporation experiment was conducted in summer to evaluate the effects of incorporation timing on pyroxasulfone, pendimethalin, and indaziflam efficacy as a measure of relative stability. Orchard weed control experiments were conducted in spring in an almond orchard near Arbuckle, CA, and a walnut orchard near Davis, CA. The orchard experiments included pyroxasulfone, pendimethalin, and indaziflam in various rate combinations with glufosinate. To evaluate crop safety, 2-year experiments were conducted to evaluate repeated applications of above-label rates of pyroxasulfone at 1199 g·ha−1 and S-metolachlor at 14,010 g·ha−1 on 1- to 2-year-old almond, pistachio, and walnut trees near Davis. Pyroxasulfone performed similarly to commercial standards with up to 95% control of broadleaf and grass weeds with pyroxasulfone and indaziflam providing 96% to 100% control of annual bluegrass, and pyroxasulfone (293 g·ha−1) being the only herbicide to suppress (>70%) common lambsquarters at 60 days after treatment (DAT). Other weeds controlled by pyroxasulfone include swinecress, redroot pigweed, yellow nutsedge, and Italian ryegrass. No differences were found among treatments in the incorporation timing study indicating adequate stability on the soil surface under summer conditions. Crop injury was not observed in the established orchards or the young orchard studies and there were no treatment effects on tree trunk diameter of almond, pistachio, and walnut in the 2-year crop safety experiments. These results indicate a potential for pyroxasulfone in California tree nut orchard systems that would be an additional site of action and beneficial for management of herbicide-resistant weeds in these crops.

Abstract Background Individual reports have described lymphoproliferative disorders (LPDs) and cutaneous lymphomas emerging after administration of the COVID‐19 vaccine; however, the relationship between reactions and vaccine types has not yet been examined. Objective Determine if there are cases of cutaneous LPDs associated with certain COVID‐19 vaccines and their outcomes. Methods We analysed PubMed, the Vaccine Adverse Events Reporting System (VAERS), and our database for instances of biopsy‐proven LPDs following COVID‐19 vaccines. Results Fifty cases of biopsy‐proven LPDs arising after COVID‐19 vaccination were found: 37 from medical literature, 11 from VAERS and two from our institution. Geographical distribution revealed the most cases in the United States, Italy, and Greece, with single cases in Spain, Colombia, Canada, Japan, and Romania. The average age of patients was 53; with a slight male predominance (male‐to‐female ratio of 1.5:1). The Pfizer‐BioNTech vaccine was associated with LPDs in 36/50 (72%) cases, aligning with its 70% share of the global vaccine market. Histopathology revealed CD30+ in 80% of cases. The most prevalent form of LPD was lymphomatoid papulosis (LyP, 30%). All reported cases produced favourable outcomes (either complete or near‐complete remission). Therapeutic approaches ranged from observation to treatment with steroids, methotrexate, or excision. Conclusion LPDs after COVID‐19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self‐limited character.

Columnaris disease is a prevalent disease in freshwater environments caused by the ubiquitous aquatic pathogen Flavobacterium species. Adhesion to the external mucosal surfaces of fishes is the initial stage of infection, and the gills specifically have been identified as both a primary target and release site for this pathogen. Demonstrated here and in previous research, the hybrid striped bass (Morone chrysops x M. saxatilis), a prominent United States aquaculture product, is more susceptible to infection with F. covae than the maternal white bass (M. chrysops) parental species. To further elucidate the mechanisms underlying differences in resistance between these fish we examined gill gene expression profiles using RNA sequencing at different timepoints after F. covae infection. Patterns of differential gene expression and association with key enrichment terms indicate the effective immune response observed in white bass includes the up-regulation of multiple cytokines (IL-1β, IL-17C, TNF-α, G-CSF, IL-8, CCL16, CXCL9), hepcidins (HAMP and HAMP2), ribosomal subunit components (e.g., RPL13), and, interestingly, the down-regulation of leptin (LEPA) during initial (1 – 4 h) stages of infection. Conversely, up-regulation of the same genes was not detected in hybrid striped bass until 24 h after infection, indicating a delay in immune response mechanisms that is ultimately ineffective in protecting the host, as this was concurrent with the onset of mortality in these fish. Collectively, the presented results include several putative pathways and candidate genes for further investigation toward characterizing immune defense mechanisms underlying the resistance (white bass) and susceptibility (hybrid striped bass) for selective breeding efforts and/or biotechnological intervention.

Abstract Wind wave observations in shallow coastal waters are essential for calibrating, validating, and improving numerical wave models to predict sediment transport, shoreline change, and coastal hazards such as beach erosion and oceanic inundation. Although ocean buoys and satellites provide near-global coverage of deep-water wave conditions, shallow-water wave observations remain sparse and often inaccessible. Nearshore wave conditions may vary considerably alongshore due to coastline orientation and shape, bathymetry and islands. We present a growing dataset of in-situ wave buoy observations from shallow waters (

Abstract Evidence from histopathology and clinical imaging suggest that choroidal anatomy and hemodynamic perfusion are among the earliest changes in retinal diseases such as age-related macular degeneration (AMD). However, how inner choroidal anatomy affects hemodynamic perfusion is not well understood. Therefore, we sought to understand the influences of choroidal microvascular architecture on the spatial distribution of hemodynamic parameters in choriocapillaris from human donor eyes using image-based computational hemodynamic (ICH) simulations. We subjected image-based inner choroid reconstructions from eight human donor eyes to ICH simulation using a kinetic-based volumetric lattice Boltzmann method to compute hemodynamic distributions of velocity, pressure, and endothelial shear stress. Here, we demonstrate that anatomic parameters, including arteriolar and venular arrangements and intercapillary pillar density and distribution exert profound influences on inner choroidal hemodynamic characteristics. Reductions in capillary, arteriolar, and venular density not only reduce the overall blood velocity within choriocapillaris, but also substantially increase its spatial heterogeneity. These first-ever findings improve understanding of how choroidal anatomy affects hemodynamics and may contribute to pathogenesis of retinal diseases such as AMD.

Background: Patients facing a cutaneous lymphoma diagnosis frequently turn to the internet for information but finding patient-accessible education may be a challenge. Objective: To investigate accessibility and readability of patient-oriented online education on cutaneous lymphomas, including cutaneous T-cell and B-cell lymphoma subtypes. Methods: This study queried a search engine for 11 cutaneous lymphoma terms, resulting in 1083 webpages. Webpages were screened using defined inclusion/exclusion criteria; literature directed to physicians and scientists was excluded. Webpages were stratified by academic/nonacademic and dermatology/nondermatology hosts and assessed by order of appearance. Readability, including text complexity, was analyzed for grade level understanding using 5 established calculators. Overall readability was assessed by Flesch–Kincaid Reading Ease. Results: Academic webpages had earlier order of appearance. There was a dearth in dermatology-hosted webpages. Rarer cutaneous lymphomas yielded fewer patient-accessible results. Search term readability significantly exceeded the American Medical Association–recommended sixth grade level (P

AbstractResearch objective Medications for opioid use disorder (MOUDs) – including methadone, buprenorphine, and naltrexone – are the most effective treatments for opioid use disorder (OUD). Historically, insurers have required prior authorization for MOUD, but prior authorization is often reported as a key barrier to MOUD prescribing. Some states have passed laws prohibiting MOUD prior authorization requirements. We sought to identify the frequency of MOUD prior authorization prohibitions in state laws and to categorize types of prohibitions.Methods We searched for regulations and statutes present in all U.S. states and Washington DC between 2005 and 2019 using MOUD-related terms in Westlaw legal software. In qualitative software, we coded laws discussing MOUD prior authorization using template analysis – a mixed deductive/inductive approach. Finally, we used coded laws to identify frequencies of states with prior authorization prohibitions, including changes over time.Results No states had laws prohibiting MOUD prior authorization between 2005 and 2015, with the first prohibition appearing in 2016. By 2019, fifteen states had MOUD prior authorization prohibitions. States varied significantly in their approach to prohibiting MOUD prior authorization. In 2019, it was more common for states to have MOUD prior authorization prohibitions applying to all insurers (n = 10 states) than to only Medicaid (n = 7 states) or only non-Medicaid insurers (n = 1 state). In 2019, general prior authorization prohibitions (n = 10 states) were more common than prohibitions only applicable to medications on the formulary, prohibitions only applicable to medications on the preferred drug list, prohibitions only applicable during the first 5 days of treatment, and prohibitions only applicable during the first 30 days of treatment.Conclusions The number of states with an MOUD prior authorization law prohibition increased in recent years. Such laws could help expand access to life-saving OUD treatments by making it easier for clinicians to prescribe MOUD.KEY MESSAGESNo states had MOUD prior authorization prohibitions between 2005 and 2015 in state statutes or regulations, and only one state had such a prohibition in 2016.By 2019, fifteen states had an MOUD prior authorization prohibition law.States varied significantly in their approach to prohibiting MOUD prior authorization, including with respect to the insurer type, duration of the prohibition, and applicable medication.

Abstract Blue carbon is carbon stored long-term in vegetated coastal ecosystems, which constitutes an important sink for atmospheric carbon dioxide (CO2). However, because methane (CH4) and nitrous oxide (N2O) have higher global warming potentials (GWP) than CO2, their production and release during organic matter diagenesis can affect the climate benefit of blue carbon. Here, we present a meta-analysis synthesizing seagrass CH4 and N2O fluxes and long-term organic carbon burial rates, and use these data to estimate the reduced climate benefit (offsets) of seagrass blue carbon using three upscaling approaches. Mean offsets for individual seagrass species (34.7% GWP20;1.0% GWP100) and globally (33.4% GWP20;7.0% GWP100) were similar, but GWP20 offsets were higher, and GWP100 offsets were lower than globally, for the Australian region (41.3% GWP20;1.1% GWP100). This study highlights the importance of using long-term organic carbon burial rates and accounting for both CH4 and N2O fluxes in future seagrass blue carbon assessments.

Abstract Background The prevalence and clinical characteristics of different etiologies of peripheral edema in dogs are unknown. Hypothesis/Objectives To determine the prevalence of different etiologies of peripheral edema, describe clinical characteristics that vary among etiologies, and report survival times. Animals Five hundred twenty‐seven dogs with peripheral edema. Methods Retrospective medical record review. Differences in clinical variables among etiology groups were assessed by Kruskal‐Wallis testing with post hoc pairwise Dunn's testing and Chi‐square testing with Monte Carlo simulation. Results The most common etiologies of peripheral edema in dogs were vasculitis (n = 193, 37%), lymphatic/venous obstruction (LVO; 114, 22%), and hypoalbuminemia (94, 18%). Right‐sided congestive heart failure (R‐CHF) was uncommon (25, 5%). Edema was localized in 377 (72%) dogs and generalized in 142 (27%) dogs, and hypoalbuminemia was more likely to cause generalized edema compared to LVO or vasculitis (P

Abstract Objective Wendler's glottoplasty (WG) is a pitch‐elevating surgery performed by laryngologists providing gender‐affirming care. The surgery creates an anterior glottic web that could theoretically cause airway concerns, either perioperatively or at the time of future procedures; such concerns are not well‐described in the literature. We seek to assess surgeon opinions on airway concerns regarding WG. Method A survey of laryngologists assessing opinions on airway considerations in glottoplasty. Results A total of 19 physicians responded, representing approximately 193 surgeries. 52.6% performed glottoplasty and the remainder responded based on experience with anterior glottic webs. Two perioperative airway complications were reported, both mild stridor that did not prevent same‐day discharge. No long‐term sequela was reported. All surveyed laryngologists endorsed an altered general anesthetic approach for future procedures, with 73.7% advocating for use of a smaller endotracheal tube. 72.2% did not have “major concerns” about future intubations, and only 5.3% thought the immediate risk of airway compromise was a “real concern.” 91.9% counsel their patients routinely but briefly on airway concerns. Open‐ended comments conveyed themes of concern for post‐operative disruption of the web more than of airway compromise. Conclusion Because glottoplasty is performed in the anterior glottis and does not significantly impact airway patency, the risk of serious airway complications appears to be minimal. Laryngologists believe future intubations require a modified approach with a smaller tube, partly due to concern for glottic web trauma. Based on this pilot study, the topic deserves greater work to standardize care and anesthetic alterations for patients with WG. Level of Evidence 5

Abstract Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 ‘4D Flow CMR Consensus Statement’. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

Abstract Large amount of plastic wastes harming the environment have raised concerns worldwide on finding alternatives to non-biodegradable plastics. Microalgae has been found as a potential source for bioplastic production, besides its more common application in the pharmaceutical and nutraceutical industry. In this study, the objective was to techno-economically evaluate the large-scale co-production of Spirulina powder as food supplements and edible bioplastic for food packaging. The scale of production was large enough to satisfy 1% of local (Thailand) plastic demand (i.e., approx. 1200 MT y−1), and 1% of the global Spirulina demand (approx. 1000 MT y−1) as food supplements. Results showed that the co-production of the Spirulina powder and bioplastic revealed an attractive venture with a payback time (PBT) as low as 2.6 y and ROI as high as 38.5%. This was because the revenues generated were as high as US$ 55.6 million y−1, despite high capital (US$ 55.7 million) and operating (US$ 34.9 million y−1) costs. Sensitivity analysis showed differences in the profitability based on variations of major parameters in the study, where the split ratio of biomass used for food supplement versus bioplastic production and the bioplastic’s selling price were found to be the most sensitive.

Abstract Navigating social hierarchies is a ubiquitous aspect of human life. Social status shapes our thoughts, feelings, and actions toward others in various ways. However, it remains unclear how trust is conferred within hierarchies and how status-related cues are used when resources are on the line. This research fills this knowledge gap by examining how ascribed, consensus-based status appearance, and perceived status appearance impact investment decisions for high- and low-status partners during a Trust Game. In a series of pre-registered experiments, we examined the degree to which participants trusted unfamiliar others with financial investments when the only available information about that person was their socioeconomic status (SES). In Study 1, SES was ascribed. Studies 2 and 3 conveyed SES with visual antecedents (clothing). Across all three experiments, participants trusted high SES partners more than low SES partners. In addition, subjective perceptions of status based on visual cues were a stronger predictor of trust than consensus-based status judgments. This work highlights a high status-trust bias for decisions where an individual’s money is on the line. In addition, high-status trust bias may occur simply because of an individual’s subjective assumptions about another’s rank.

ABSTRACT: Background: Aortic diameter growth in type B aortic dissection (TBAD) is associated with progressive aortic dilation, resulting in increased mortality in patients with both de novo TBAD (dnTBAD) and residual dissection after type A dissection repair (rTAAD). Preemptive thoracic endovascular aortic repair may improve mortality in patients with TBAD, although it is unclear which patients may benefit most from early intervention. In vivo hemodynamic assessment using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has been used to characterize TBAD patients with growing aortas. In this longitudinal study, we investigated whether changes over time in 4D flow-derived true and false lumen (TL and FL) hemodynamic parameters correlate with aortic growth rate, which is a marker of increased risk. Methods: We retrospectively identified TBAD patients with baseline and follow-up 4D flow CMR at least 120 days apart. Patients with TBAD intervention before baseline or between scans were excluded. 4D flow CMR data analysis included segmentation of the TL and FL, followed by voxel-wise calculation of TL and FL total kinetic energy (KE), maximum velocity (MV), mean forward flow (FF), and mean reverse flow (RF). Changes over time (Δ) were calculated for all hemodynamic parameters. Maximal diameter in the descending aorta was measured from magnetic resonance angiogram images acquired at the time of 4D flow. Aortic growth rate was defined as the change in diameter divided by baseline diameter and standardized to scan interval. Results: Thirty-two patients met inclusion criteria (age: 56.9 ± 14.1 years, female: 13, n = 19 rTAAD, n = 13 dnTBAD). Mean follow-up time was 538 days (range: 135–1689). Baseline aortic diameter did not correlate with growth rate. In the entire cohort, Δ FL MV (Spearman’s rho [rho] = 0.37, p = 0.04) and Δ FL RF (rho = 0.45, p = 0.01) correlated with growth rate. In rTAAD only, Δ FL MV (rho = 0.48, p = 0.04) and Δ FL RF (rho = 0.51, p = 0.03) correlated with growth rate, while in dnTBAD only, Δ TL KE (rho = 0.63, p = 0.02) and Δ TL MV (rho = 0.69, p = 0.01) correlated with growth rate. Conclusion: 4D flow-derived longitudinal hemodynamic changes correlate with aortic growth rate in TBAD and may provide additional prognostic value for risk stratification. 4D flow MRI could be integrated into existing imaging protocols to allow for the identification of TBAD patients who would benefit from preemptive surgical or endovascular intervention.

Abstract Animal‐sourced hydrogels, such as collagen, are widely used as extracellular‐matrix (ECM) mimics in tissue engineering but are plagued with problems of reproducibility, immunogenicity, and contamination. Synthetic, chemically defined hydrogels can avoid such issues. Despite the abundance of collagen in the ECM, synthetic collagen hydrogels are extremely rare due to design challenges brought on by the triple‐helical structure of collagen. Sticky‐ended symmetric self‐assembly (SESSA) overcomes these challenges by maximizing interactions between the strands of the triple helix, allowing the assembly of collagen‐mimetic peptides (CMPs) into robust synthetic collagen nanofibers. This optimization, however, also minimizes interfiber contacts. In this work, symmetric association states for the SESSA of short CMPs to probe their increased propensity for interfiber association are modelled. It is found that 33‐residue CMPs not only self‐assemble through sticky ends, but also form hydrogels. These self‐assemblies behave with remarkable consistency across multiple scales and present a clear link between their triple‐helical architecture and the properties of their hydrogels. The results show that SESSA is an effective and robust design methodology that enables the rational design of synthetic collagen hydrogels.

Many active materials have properties that make them challenging to design with or limit their utility, including having combinations of nonlinear, viscous, slow, or small responses. In this work, we show that by designing metamaterial unit cells that have separately active and, specifically geometrically nonlinear, passive elements, many of these drawbacks can be mitigated and enhanced performance enabled (specifically, large, rapid, and resettable shape change). This separation between active and passive elements is advantageous, in that the complex active materials can be assigned only where needed, with the simplest geometries and functions. The use of geometric nonlinearity in passive elements is helpful as it provides mechanisms for augmented performance and further simplifies the role of the active elements. While all elements of the microstructural motifs used herein have been previously seen elsewhere, we suggest that the contribution provided here is a conceptual design approach that may be used more broadly for enabling new types of high-performing, stimuli-responsive metamaterials.

Introduction/Objective: Osteochondral allografting can be an effective option for the treatment of focal cartilage injuries. However, wide scale applicability of this technique is limited by availability of donor tissue. To overcome this limitation, osteochondral xenografting has been proposed as a potential alternative, but immune-mediated rejection precludes its clinical application at this time. We hypothesized that removing much of the marrow cell content through tissue culture would result in a decrease in xenograft immunogenicity. We believed this could be tested in a preclinical animal model. Methods: Fresh porcine femoral condyles were harvested and cultured for 0, 14, or 28 days before coculture with either allogeneic enriched porcine T-cells or xenogeneic enriched equine T-cells for 5 days. After 5 days, these cocultures were pulsed with 5-ethynyl-2′deoxyuridine then analyzed by flow cytometry to assess the level of cell proliferation. Coculture supernatant samples were also collected to evaluate the levels of prostaglandin-E2 and monocyte chemotactic protein-1 (MCP-1) as markers of inflammation. Results: The osteochondral tissue induced significantly less T-cell proliferation, prostaglandin-E2, and MCP-1 production when the tissue had been cultured for either 14 or 28 days prior to the coculture assay (P < .0001). Conclusions: We conclude that T-cell responses to either allogeneic or xenogeneic osteochondral tissues were significantly reduced by 14 days of preculture prior to exposure to T-cells.

Background: Although use of buprenorphine for treating opioid use disorder increased over the past decade, buprenorphine utilization remains limited in lower-income and rural areas. We examine how the Affordable Care Act Medicaid expansion influenced buprenorphine initiation rates by county income and evaluate how associations differ by county rural-urban status. Methods: This study used nationwide 2009–2018 IQVIA retail pharmacy data and a comparative interrupted time series framework–a hybrid framework combining regression discontinuity and difference-in-difference approaches. We used piecewise linear estimation to quantify changes in buprenorphine initiation rates before and after Medicaid expansion. Results: The sample included observations from 376,704 county-months. We identified 5,227,340 new buprenorphine treatment episodes, with an average of 9.2 new buprenorphine episodes per month per 100,000 county residents. Among urban counties, those with the lowest median incomes experienced significantly larger increases in buprenorphine initiation rates associated with Medicaid expansion than counties with higher median incomes (5-year rates difference est=3525.3, se=1695.3, p = 0.04). However, among rural counties, there was no significant association between buprenorphine initiation rates and county median income after Medicaid expansion (5-year rates difference est=979.0, se=915.8, p = 0.29). Conclusions: Medicaid expansion was associated with a reduction in income-related buprenorphine disparities in urban counties, but not in rural counties. To achieve more equitable buprenorphine access, future policies should target low-income rural areas.

Abstract Principal neurons (PNs) of the lateral superior olive nucleus (LSO) in the brainstem of mammals compare information between the two ears and enable sound localization on the horizontal plane. The classical view of the LSO is that it extracts ongoing interaural level differences (ILDs). Although it has been known for some time that LSO PNs have intrinsic relative timing sensitivity, recent reports further challenge conventional thinking, suggesting the major function of the LSO is detection of interaural time differences (ITDs). LSO PNs include inhibitory (glycinergic) and excitatory (glutamatergic) neurons which differ in their projection patterns to higher processing centers. Despite these distinctions, intrinsic property differences between LSO PN types have not been explored. The intrinsic cellular properties of LSO PNs are fundamental to how they process and encode information, and ILD/ITD extraction places disparate demands on neuronal properties. Here we examine the ex vivo electrophysiology and cell morphology of inhibitory and excitatory LSO PNs in mice. Although overlapping, properties of inhibitory LSO PNs favor time coding functions while those of excitatory LSO PNs favor integrative level coding. Inhibitory and excitatory LSO PNs exhibit different activation thresholds, potentially providing further means to segregate information in higher processing centers. Near activation threshold, which may be physiologically similar to the sensitive transition point in sound source location for LSO, all LSO PNs exhibit single-spike onset responses that can provide optimal time encoding ability. As stimulus intensity increases, LSO PN firing patterns diverge into onset-burst cells, which can continue to encode timing effectively regardless of stimulus duration, and multi-spiking cells, which can provide robust individually integrable level information. This bimodal response pattern may produce a multi-functional LSO which can encode timing with maximum sensitivity and respond effectively to a wide range of sound durations and relative levels.

Stanford type B aortic dissection (TBAD) is a potentially fatal condition involving a tear in the descending aorta. As TBAD can be managed with medical therapy or surgical repair, identifying predictors of adverse outcomes is important to risk-stratify patients for preemptive surgical procedures. 4D flow magnetic resonance imaging (MRI) has shown to be useful in characterizing the complex hemodynamics seen in TBAD patients and correlating flow patterns with adverse outcomes. We report a case of a 58-year-old man who presented to the hospital with acute TBAD and a large primary entry tear. He was initially managed with medical therapy due to his stable clinical status and computed tomographic angiography showing a stable dissection. However, 4D flow MRI showed high velocity flow through the entry tear, which foreshadowed the later clinical decompensation of the patient. Our case demonstrates that performing 4D flow MRI on TBAD patients is feasible and can provide valuable information in the decision to pursue medical or surgical management.

Alberta’s forest industry is predicted to be impacted by a medium-term decline in timber supply. Intensive silviculture tools, such as pre-commercial thinning, have been shown to increase individual tree growth, shorten rotation lengths, and improve stand merchantability in important commercial species such as lodgepole pine. However, lodgepole pine stands are susceptible to western gall rust infections, and thinning at an early stage may increase infection rates. This study collected tree and stand level data from 33 operational harvest origin lodgepole pine stands consisting of 11 stands thinned at age 17–19 years (PCT_18), 11 stands thinned at age 23–25 (PCT_24), and 11 unthinned stands. Approximately 40 years after pre-commercial thinning, merchantable volume is similar in all stands but thinned stands, regardless of timing, had greater individual tree size (~15% higher) compared to unthinned stands. Pre-commercially thinned stands also had a higher potential for commercial thinning since they have lower variability in tree size and longer live crown lengths. In addition, delayed thinning (PCT_24) reduced western gall rust infections and the severity of infections compared to both PCT_18 and unthinned stands. In conclusion, pre-commercial thinning should be considered for lodgepole pine stands in order to address timber supply issues in Alberta.

The genetic basis of horn fly abundance remains largely unknown and only few heritability estimates are available based on small scale studies. In this study, one subjective and two image-based fly abundance phenotypes were analyzed. Each animal was assessed subjectively for fly abundance by at least one trained agent (SUB). Additionally, several digital images were taken and the best image for each animal was used to assess fly abundance. A box that runs roughly from the withers to the hook and from the chest floor to the fore of the udder was established and all horn flies (PA) and sampling-based estimated number of flies (PR) within the box were calculated. Horn fly counts (SUB, PA, and PR) were discretized into 4 classes based on the quartiles of their respective distributions. Heritability estimates ranged between 0.10 and 0.15 and between 0.14 and 0.16 for the continuous and discrete cases, respectively. The genetic correlation was 0.66 between PA and PR and decreased significantly between the image-based (PA and PR) and the subjective (SUB) assessments for the continuous case. For the discrete case, the genetic correlations between the three traits were very similar, indicating a high concordance between traits.

The increasing availability and quality of high-resolution bathymetry data has led to a growing need for automated classification approaches to extract seabed features and better understand our ever-changing and complex seascapes. Here we present a new set of GIS tools designed to classify seabed landforms on continental and island shelf settings. The classification approach utilises bathymetry data and its derivatives of slope, ruggedness and bathymetric position index to delineate key components of the seabed surface. The user is guided through a series of steps to break down the seabed surface into components termed ‘surface elements’ (e.g. smooth, rugose, slope areas), which are subsequently grouped into prominent seabed features termed ‘seabed landforms’ (e.g. reefs, channels, scarps). Manual review and editing are incorporated into the workflow, striking a balance between automation and expert manual interpretation. We present the toolset using examples from the statewide marine lidar dataset from New South Wales, Australia, and explore tool settings using bathymetric data representing different data sources (multibeam and marine lidar), environmental seascapes, data resolutions (2, 5, 10 and 20 m cell size) and data preparation treatments (with and without data smoothing). The GIS toolset presented offers an effective and flexible method to extract key features from high-resolution shelf bathymetry data. Such mapping provides fundamental baseline data for vast applications within marine planning, research and management.

Threespike goosegrass (Eleusine tristachya) is a difficult-to-control perennial grass of increasing concern for orchard production systems in the Central Valley of California, USA. This grass has a bunch-type growth habit when tillered, which can interfere with orchard operations, particularly nut pickup from the ground at harvest. From 2016 to 2019, herbicide efficacy on threespike goosegrass was evaluated in a walnut (Juglans regia) orchard in Chico, CA, USA; an almond (Prunus dulcis) orchard in Livingston, CA, USA; and a prune (Prunus domestica) orchard in Orland, CA, USA. At each location, two independent experiments were conducted to evaluate 12 preemergent (PRE) herbicide treatments and eight postemergent (POST) treatments over several years, for a total of 16 trials. PRE herbicides were applied in January according to the region’s typical winter orchard management practices. One treatment included an additional sequential application in March to extend residual activity later into the warm season when threespike goosegrass germinates or resumes growth. In separate studies, POST control of established stands of threespike goosegrass was evaluated in May and June of each year. Each trial was conducted in a randomized complete block design with four replications. Threespike goosegrass control was visually estimated monthly for 5 months after the PRE treatments or at weekly intervals for 5 weeks following POST treatments. The most effective PRE treatment was a sequential application of indaziflam in January, followed by a March application of pendimethalin, providing 90% or greater control of threespike goosegrass 5 months after treatment across all sites and all years. Of the POST treatments, the three graminicides outperformed the other treatments with 73% to 91% control overall sites and years at 5 weeks after treatment. Fluazifop had the highest control ratings (85% to 91%) among the graminicide herbicides but was not always statistically better than clethodim or sethoxydim (74% to 83% control). Glyphosate alone resulted in unacceptable control (33% to 51%) regardless of rates tested, experimental sites, or years. Together, these results confirm grower reports of poor glyphosate performance on threespike goosegrass but suggest that effective herbicide programs can be developed to manage threespike goosegrass using PRE herbicides and POST graminicides registered in California orchard crops.

Abstract Background Bicuspid aortic valve (BAV) disease is associated with increased risk of aortopathy. In addition to current intervention guidelines, BAV mediated changes in aortic 3D hemodynamics have been considered as risk stratification measures. We aimed to evaluate the association of 4D flow cardiovascular magnetic resonance (CMR) derived voxel-wise aortic reverse flow with aortic dilation and to investigate the role of aortic valve regurgitation (AR) and stenosis (AS) on reverse flow in systole and diastole. Methods 510 patients with BAV (52 ± 14 years) and 120 patients with trileaflet aortic valve (TAV) (61 ± 11 years) and mid-ascending aorta diameter (MAAD) > 35 mm who underwent CMR including 4D flow CMR were retrospectively included. An age and sex-matched healthy control cohort (n = 25, 49 ± 12 years) was selected. Voxel-wise reverse flow was calculated in the aorta and quantified by the mean reverse flow in the ascending aorta (AAo) during systole and diastole. Results BAV patients without AS and AR demonstrated significantly increased systolic and diastolic reverse flow (222% and 13% increases respectively, p 17% increase, p 27% decrease, p 0.1). Conclusion 4D flow CMR derived reverse flow associated with BAV was successfully captured even in the absence of AR or AS and in comparison to TAV patients with aortic dilation. Diastolic AAo reverse flow increased with AR severity while AS severity strongly correlated with increased systolic reverse flow in the AAo. Additionally, increasing MAAD was independently associated with increasing systolic AAo reverse flow. Thus, systolic AAo reverse flow may be a valuable metric for evaluating disease severity in future longitudinal outcome studies.

The design of efficient single-atom catalysts (SACs) with optimal activity and selectivity for sustainable energy and environmental applications remains a challenge. In this work, comprehensive first-principles calculations are performed to validate the feasibility of single TM atoms ( 3d , 4d , and 5d series) embedded in two different conformations of graphitic carbon nitride (g-C _3 N _4 ) monolayers. Additionally, we investigate the effect of nitrogen vacancies in the g-C _3 N _4 monolayers on the absorption of SACs considering three potential absorption scenarios that correspond to different experimental conditions. Our results point to the most stable configurations with the lowest formation energies and indicate that the absorption of single TM atoms on-vacancy and on-center sites are more favorable than via-substitution. In addition to the thermodynamic stability, electrochemical stability is also investigated through the calculation of the dissolution potential of the SACs. Within the scenarios considered in this study, we find that Pt, Pd, Rh, Au, Ru, Ir, Cu, Co, Fe, and Ni will produce the most robust SACs on both (edge and bridge) N vacancy site of reduced g-C _3 N _4 . Our findings provide guidance for the design and development of g-C _3 N _4 sheets decorated with single TM atoms for technological applications such as pollutant degradation, CO _2 reduction, N _2 fixation, selective oxidation, water splitting, and metal ion-based batteries.

Abstract Background Large vessel vasculitis (LVV) can be characterized based on symptom severity, and this characterization helps clinicians decide upon treatment approach. Our aim was to compare the imaging findings of combined modality positron emission tomography/magnetic resonance (PET/MR) and inflammatory markers between severe and non-severe LVV. A retrospective query was performed to identify all patients with LVV who underwent PET/MR at our institution between January 2015 and January 2021. Results Eleven patients (nine females; age 62.2 ± 16.4 years) underwent 15 PET/MR scans. Positivity was defined by findings indicative of active LVV on each modality: PET positive if vessel metabolic activity > liver metabolic activity; MR positive if wall thickening or contrast enhancement. When positive PET or positive MR findings were considered a positive scan, LVV patients with severe disease (n = 9 scans) showed a higher number of positive scans (n = 9) compared to the number of positive scans in non-severe patients (n = 3) (p

Abstract Dietary emulsifier consumption promotes systemic low-grade inflammation, metabolic deregulation, and possibly an anxiety-like phenotype. The latter finding suggests that dietary emulsifiers impact brain areas that modulate stress responses. The goal of the current study was to test whether emulsifier consumption is associated with changes in gene expression in the amygdala and the paraventricular nucleus of the hypothalamus (PVN), two brain areas that are involved in behavioral and neuroendocrine responses to stress. Using RNA-Seq, we compared groups consuming either carboxymethylcellulose or polysorbate 80 for 12-weeks. A total of 243 genes were differentially expressed in the amygdala and PVN of emulsifier-treated mice compared to controls. There was minimal overlap of differentially expressed genes in CMC- and P80-treated animals, suggesting that each emulsifier acts via distinct molecular mechanisms to produce an anxiety-like phenotype. Furthermore, gene ontology and pathway analysis revealed that various stress, metabolic, and immune terms and pathways were altered by emulsifiers. These findings are the first to demonstrate that emulsifier consumption changes gene expression in brain regions that are critical for stress responding, providing possible molecular mechanisms that may underly the previously observed anxiety-like phenotype.

Abstract Conodonts are an extinct group of primitive jawless vertebrates whose elements represent the earliest examples of a mineralized feeding apparatus in vertebrates. Their relative relationship within vertebrates remains unresolved. As teeth, conodont elements are not homologous with the dentition of vertebrates, but they exhibit similarities in mineralization, growth patterns, and function. They clearly represent an early evolutionary experiment in mineralized dentition and offer insight into analogous dentition in other groups. Unfortunately, analysis of functional performance has been limited to a handful of derived morphologies and material properties that may inform ecology and functional analysis are virtually unknown. Here we applied a nanoscale approach to evaluate material properties of conodont bioapatite by utilizing Atomic Force Microscopy (AFM) nanoindentation to determine Young’s modulus (E) along multiple elements representing different ontogenetic stages of development in the coniform-bearing apparatus of Dapsilodus obliquicostatus. We observed extreme and systematic variation in E along the length (oral to aboral) of each element that largely mirrors the spatial and ontogenetic variability in the crystalline structure of these specimens. Extreme spatial variability of E likely contributed to breakage of elements that were regularly repaired/regrown in conodonts but later vertebrate dentition strategies that lacked the ability to repair/regrow likely required the development of different material properties to avoid structural failure.

Artificial microswimmers can emulate the autonomous regulation of chemotactic motility of living organisms. Frank et al. realize a chemotactic locomotion of emulsion droplets, composed of two phase-separated fluids, that can be reversibly directed up or down a chemical concentration gradient.