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Abstract Sustainable livestock production requires links between farm characteristics, animal performance and animal health to be recognised and understood. In the pig industry, respiratory disease is prevalent, and has negative health, welfare and economic consequences. We used national-level carcass inspection data from the Food Standards Agency to identify associations between pig respiratory disease, farm characteristics (housing type and number of source farms), and pig performance (mortality, average daily weight gain, back fat and carcass weight) from 49 all in/all out grow-to-finish farms. We took a confirmatory approach by pre-registering our hypotheses and used Bayesian multi-level modelling to quantify the uncertainty in our estimates. The study findings showed that acquiring growing pigs from multiple sources was associated with higher respiratory condition prevalence. Higher prevalence of respiratory conditions was linked with higher mortality, and lower average daily weight gain, back fat and pig carcass weight. Our results support previous literature using a range of data sources. In conclusion, we find that meat inspection data are more valuable at a finer resolution than has been previously indicated and could be a useful tool in monitoring batch-level pig health in the future.

Early academic skills and behavioral characteristics in students are predictive of later school achievement, but academics and behavior are commonly compartmentalized in research and practice. This study investigated to what extent first-grade early numeracy (EN), literacy, and behavior ratings predicted fourth-grade mathematics achievement. In fall of first-grade, 501 students were given EN and literacy measures and a behavior rating scale completed by their teachers. In spring of fourth-grade, students were given mathematics computation and concepts assessments. Regression analyses indicated EN, early literacy, and behavior uniquely predicted 39% of the variance in participants' fourth-grade mathematics achievement. Significant predictors were EN and behavior ratings (p < 0.001), which accounted for 29% and 9% of the variance in mathematics scores, respectively.

Abstract Background Lyme disease is emerging in Canada due to expansion of the range of the tick vector Ixodes scapularis from the United States. National surveillance for human Lyme disease cases began in Canada in 2009. Reported numbers of cases increased from 144 cases in 2009 to 2025 in 2017. It has been claimed that few (

Mathematical writing (MW) can support students' mathematical learning and is common in mathematics assessment. However, MW is known to be particularly challenging for students with learning disabilities. While the use of model compositions of both high- and low-quality writing and the act of revision are evidence-based practices in writing instruction, models of MW are not readily available in the curriculum, and many teachers struggle to compose high-quality MW themselves. Artificial intelligence (AI) chatbots are increasingly accessible for teachers and provide one avenue by which MW models can be readily generated. This column guides educators on utilizing AI chatbots to produce MW models to support MW instruction for students with learning disabilities.

Abstract While Alzheimer’s disease and other neurodegenerative diseases have traditionally been viewed as brain disorders, there is growing evidence indicating their manifestation in the eyes as well. The retina, being a developmental extension of the brain, represents the only part of the central nervous system that can be noninvasively imaged at a high spatial resolution. The discovery of the specific pathological hallmarks of Alzheimer’s disease in the retina of patients holds great promise for disease diagnosis and monitoring, particularly in the early stages where disease progression can potentially be slowed. Among various retinal imaging methods, hyperspectral imaging has garnered significant attention in this field. It offers a label-free approach to detect disease biomarkers, making it especially valuable for large-scale population screening efforts. In this review, we discuss recent advances in the field and outline the current bottlenecks and enabling technologies that could propel this field toward clinical translation.

The configuration of the Northern Hemisphere ice sheets during the Penultimate Glacial Maximum differed to the Last Glacial Maximum. However, the reasons for this are not yet fully understood. These differences likely contributed to the varied deglaciation pathways experienced following the glacial maxima and may have had consequences for the interglacial sea level rise. To understand the differences between the North American Ice Sheet at the Last and Penultimate glacial maxima (21 and 140 ka), we perform two perturbed-physics ensembles of 62 simulations using a coupled atmosphere–ice sheet model, FAMOUS-ice, with prescribed surface ocean conditions, in which the North American and Greenland ice sheets are dynamically simulated with the Glimmer ice sheet model. We apply an implausibility metric to find ensemble members that match reconstructed ice extent and volumes at the Last and Penultimate glacial maxima. We use a resulting set of “plausible” parameters to perform sensitivity experiments to decompose the role of climate forcings (orbit, greenhouse gases) and initial conditions on the final ice sheet configurations. This confirms that the initial ice sheet conditions used in the model are extremely important in determining the difference in final ice volumes between both periods due to the large effect of the ice–albedo feedback. In contrast to evidence of a smaller Penultimate North American Ice Sheet, our results show that the climate boundary conditions at these glacial maxima, if considered in isolation, imply a larger Penultimate Glacial Maximum North American Ice Sheet than at the Last Glacial Maximum by around 6 m sea level equivalent. This supports the notion that the growth of the ice sheet prior to the glacial maxima is key in explaining the differences in North American ice volume.

The Last Glacial Maximum (LGM) was characterised by huge ice sheets covering the Northern Hemisphere, especially over North America, and by its cold climate. Previous authors have performed numerical simulations of the LGM to better understand coupled climate–ice sheet systems. However, the results of such simulations are sensitive to many model parameters. Here, we perform a 200-member ensemble of simulations of the North American and Greenland ice sheets and climate of the LGM with a coupled ice sheet–atmosphere–slab ocean model (FAMOUS-BISICLES) to explore sensitivities of the coupled climate–ice system to 16 uncertain parameters. In the ensemble of simulations, the global mean surface temperature is primarily controlled by the combination of parameters in the large-scale condensation scheme and the cumulus convection scheme. In simulations with plausible LGM global mean surface temperatures, we find that the albedo parameters have only a small impact on the Greenland ice volume due to the limited area of surface ablation associated with the cold climate. Instead, the basal sliding law controls the ice volume by affecting ice transport from the interior to the margin. On the other hand, like the Greenland ice sheet in future climate change, the LGM North American ice sheet volume is controlled by parameters in the snow and ice albedo scheme. Few of our simulations produce an extensive North American ice sheet when the global temperature is above 12 °C. Based on constraints on the LGM global mean surface temperature, the ice volume and the southern extent of the North American ice sheet, we select 16 acceptable simulations. These simulations lack the southern extent of ice compared to reconstructions, but they show reasonable performance on the ice sheet configuration and ice streams facing Baffin Bay and the Arctic Ocean. The strong sensitivities of the North American ice sheet to albedo at the LGM may imply a potential constraint on the future Greenland ice sheet by constraining the albedo schemes.

ABSTRACT Background To investigate the feasibility of conducting COVID‐19 testing in kindergarten‐grade 12 schools, saliva‐based testing was implemented in five schools. The purpose of this study was to understand staff's perspectives of the barriers and facilitators to conducting saliva‐based testing in their settings. Methods Thirty‐three school staff who worked in five target schools were interviewed in the summer of 2021. Participants were recruited from June–August 2021 via a flyer that was distributed through email and school‐affiliated social media and websites, and word‐of‐mouth. Semi‐structured interviews were conducted over Zoom by a trained interviewer; interviews were audio recorded and auto transcribed using this Zoom feature. Constant comparative analysis and emergent coding were used to analyze the data. Results The majority of participants had positive experiences with conducting saliva‐based testing during school hours. Participants reported that saliva‐based testing did not interrupt their school routine because (1) the testing was simple and quick, (2) the testing schedule was consistent and organized, and (3) school staff maintained open lines of communication. Barriers to implementing the testing were as follows: (1) obtaining parental consent, (2) not being allowed to drink or eat an hour before testing, and (3) struggling to provide enough saliva for testing. Participants suggested the following strategies to facilitate testing in schools: being more proactive, giving families fewer things to sign (i.e., consent forms), improving communication, adding needed consents to the school registration process, using social media, and increasing community outreach. Conclusion As schools weigh the benefits and the risks of closing for extended periods of time versus remaining open for in‐person learning, saliva‐based testing is a feasible and efficient way to support programs in this decision‐making process. This approach can be used in future pandemics and in areas with outbreaks or poor vaccine coverage.

ABSTRACTCOVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19.

IntroductionDietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link.ObjectiveTo investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status.MethodsThis study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors.ResultsOver 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes.ConclusionEncouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.

The disturbed atmospheric pressure near a wind farm arises from the turbine drag forces in combination with vertical confinement associated with atmospheric stability. These pressure gradients slow the wind upstream, deflect the air laterally, weaken the flow deceleration over the farm, and modify the farm wake recovery. Here, we describe the airflow and pressure disturbance near a wind farm under typical stability conditions and, alternatively, with the simplifying assumption of a rigid lid. The rigid lid case clarifies the cause of the pressure disturbance and its close relationship to wind farm drag. The key to understanding the rigid lid model is the proof that the pressure field p(x,y) is a harmonic function almost everywhere. It follows that the maximum and minimum pressure occur at the front and back edge of the farm. Over the farm, the favorable pressure gradient is constant and significantly offsets the turbine drag. Upwind and downwind of the farm, the pressure field is a dipole given by p(x,y)≈Axr-2, where the coefficient A is proportional to the total farm drag. Two derivations of this law are given. Field measurements of pressure can be used to find the coefficient A and thus to estimate total farm drag.

The Antarctic Ice Sheet represents the largest source of uncertainty in future sea level rise projections, with a contribution to sea level by 2100 ranging from −5 to 43 cm of sea level equivalent under high carbon emission scenarios estimated by the recent Ice Sheet Model Intercomparison for CMIP6 (ISMIP6). ISMIP6 highlighted the different behaviors of the East and West Antarctic ice sheets, as well as the possible role of increased surface mass balance in offsetting the dynamic ice loss in response to changing oceanic conditions in ice shelf cavities. However, the detailed contribution of individual glaciers, as well as the partitioning of uncertainty associated with this ensemble, have not yet been investigated. Here, we analyze the ISMIP6 results for high carbon emission scenarios, focusing on key glaciers around the Antarctic Ice Sheet, and we quantify their projected dynamic mass loss, defined here as mass loss through increased ice discharge into the ocean in response to changing oceanic conditions. We highlight glaciers contributing the most to sea level rise, as well as their vulnerability to changes in oceanic conditions. We then investigate the different sources of uncertainty and their relative role in projections, for the entire continent and for key individual glaciers. We show that, in addition to Thwaites and Pine Island glaciers in West Antarctica, Totten and Moscow University glaciers in East Antarctica present comparable future dynamic mass loss and high sensitivity to ice shelf basal melt. The overall uncertainty in additional dynamic mass loss in response to changing oceanic conditions, compared to a scenario with constant oceanic conditions, is dominated by the choice of ice sheet model, accounting for 52 % of the total uncertainty of the Antarctic dynamic mass loss in 2100. Its relative role for the most dynamic glaciers varies between 14 % for MacAyeal and Whillans ice streams and 56 % for Pine Island Glacier at the end of the century. The uncertainty associated with the choice of climate model increases over time and reaches 13 % of the uncertainty by 2100 for the Antarctic Ice Sheet but varies between 4 % for Thwaites Glacier and 53 % for Whillans Ice Stream. The uncertainty associated with the ice–climate interaction, which captures different treatments of oceanic forcings such as the choice of melt parameterization, its calibration, and simulated ice shelf geometries, accounts for 22 % of the uncertainty at the ice sheet scale but reaches 36 % and 39 % for Institute Ice Stream and Thwaites Glacier, respectively, by 2100. Overall, this study helps inform future research by highlighting the sectors of the ice sheet most vulnerable to oceanic warming over the 21st century and by quantifying the main sources of uncertainty.

In this chapter we provide an overview of campus ecology and ecological systems theory as applied to the study of higher education, most often to research on college students. We describe Bronfenbrenner's developmental ecological model and its application of it to the study of college students. We then discuss affordances and limitations of this approach, including criticism of its lack of attention to systems of privilege and oppression in the higher education environment. We present a number of innovative approaches to using the Bronfenbrenner model that address these limitations, as well as adaptations to the model that incorporate critical theory, queer theory, and Indigenous Knowledge Systems.

Abstract INTRODUCTION The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World‐Wide FINGERS (WW‐FINGERS). As part of WW‐FINGERS, the Australian AU‐ARROW study mirrors aspects of FINGER, as well as US‐POINTER. METHOD AU‐ARROW is a randomized, single‐blind, multisite, 2‐year clinical trial (n = 600; aged 55–79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. DISCUSSION The finalized AU‐ARROW protocol is expected to allow development of an evidence‐based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Highlights Study protocol for a single‐blind, randomized controlled trial, the AU‐ARROW Study. The AU‐ARROW Study is a member of the World‐Wide FINGERS (WW‐FINGERS) initiative. AU‐ARROW's primary outcome measure is change in a global composite cognitive score. Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests. Leading to development of an innovative treatment plan to reduce cognitive decline.

Abstract INTRODUCTION This study investigated whether self‐reported sleep quality is associated with brain amyloid beta (Aβ) accumulation. METHODS Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self‐reported sleep data, and positron emission tomography‐determined brain Aβ measured over a minimum of three time points (range 33.3–72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) ε4 allele status, and time, adjusting for sex and baseline age. RESULTS Sleep duration

Abstract Background Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en‐bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral diaphragm. Small case series of pleural‐based sarcoma of predominantly pediatric patients suggest EPP may be a life‐prolonging surgical option. We aimed to describe the characteristics and outcomes of adults who underwent EPP at a specialized sarcoma center. Methods Clinicopathologic variables, surgical details, and follow‐up information were extracted for patients undergoing EPP for pleural‐based sarcoma between August 2017 and December 2020. Primary outcomes were event‐free survival (EFS) and overall survival (OS) from the date of EPP. Secondary outcomes were disease‐free interval (DFI) prior to EPP, and early and late postoperative complications. Results Eight patients were identified, seven with soft tissue sarcoma and one with bone sarcoma. Patients had either localized disease with a primary thoracic sarcoma, sarcoma recurrent to the thorax, or de novo metastatic disease. All patients underwent resection of their pleural‐based sarcoma by an experienced cardiothoracic surgeon, and some patients had pre or postoperative treatment. The perioperative morbidity was comparable with previously published reports of EPP performed in mesothelioma patients. At median follow‐up of 22.5 months, median EFS was 6.0 months and OS was 20.7 months. Six patients (75%) had disease recurrence; five (62.5%) died of progressive disease. Two patients (25%) had not recurred: one died of a radiation‐related esophageal rupture, and one was alive with no evidence of disease at 37.0 months. Characteristics of those with the longest EFS included low‐grade histology and achieving a metabolic response to preoperative chemotherapy. Conclusions In adults with pleural‐based sarcoma, EPP is rarely curative but appears to be a feasible salvage procedure when performed at specialized centers. Patient selection is critical with strong consideration given to multimodal therapy to optimize patient outcomes. In the absence of a confirmed response to neoadjuvant treatment, long term survival is poor and EPP should not be recommended.

Abstract Introduction Approximately one third of patients with Acute Type A Aortic Dissection (ATAAD) present with pre-operative malperfusion syndromes (MPS). Of these, mesenteric malperfusion represents the greatest risk to patients with respect to increased short-term mortality. In select patients, it may be feasible to offer a staged approach by treating the mesenteric malperfusion first, optimizing the patient in the intensive care setting and then, following with a central aortic repair. The aim of this systematic review is to summarize cohort studies assessing the role of pre-operative interventions for mesenteric malperfusion. Methods An electronic literature search of five databases was performed to identify all relevant studies providing studies examining short-term mortality on patients who underwent either endovascular or open revascularisation of mesenteric ischemia prior to central aortic repair. The primary outcome was all-cause, short-term mortality. Secondary outcomes were comparative mortality between a delayed repair vs. aortic repair first strategy, rates of postoperative laparotomy, bowel resection, and mortality following delayed aortic repair. Results The search strategy identified 8 studies qualifying for inclusion, with a total of 180 patients who underwent delayed aortic surgery in the setting of mesenteric MPS. The weighted short-term mortality following a mesenteric revascularisation first, delayed aortic surgery strategy was 22.5%. This strategy was also associated with a significantly lower mortality than a central repair first strategy (OR 0.07, 95% CI 0.02–0.27), and a significantly lower rate of postoperative laparotomy/bowel resection (OR 0.05, 95% CI 0.02–0.14). If patients survive to receive central repair, the weighted short-term mortality postoperatively is low (2.1%). Conclusion A summary of this evidence reveals a lower short-term mortality in hemodynamically stable patients with mesenteric malperfusion, along with a reduction in postoperative laparotomy/bowel resections. Of those patients who survive to receive central repair, short-term mortality remains very low in the select group of hemodynamically stable patients. Further high-quality studies with randomized or propensity matched data are required to verify these results.

Abstract Spectral imaging holds great promise for the non-invasive diagnosis of retinal diseases. However, to acquire a spectral datacube, conventional spectral cameras require extensive scanning, leading to a prolonged acquisition. Therefore, they are inapplicable to retinal imaging because of the rapid eye movement. To address this problem, we built a coded aperture snapshot spectral imaging fundus camera, which captures a large-sized spectral datacube in a single exposure. Moreover, to reconstruct a high-resolution image, we developed a robust deep unfolding algorithm using a state-of-the-art spectral transformer in the denoising network. We demonstrated the performance of the system through various experiments, including imaging standard targets, utilizing an eye phantom, and conducting in vivo imaging of the human retina.

BackgroundFew studies have considered the life-course development of depressive symptoms in relation to life transitions in early-adulthood and whether these might affect depressive trajectories differently depending on specific indicators of parental socioeconomic status (SES). In the present work, we explore these questions using the adolescent pathway model as a guiding framework to test socially differential exposure, tracking and vulnerability of the effects of life transitions on depressed mood across different socioeconomic backgrounds.MethodsLatent growth modeling was used to estimate the associations between indicators of parental SES (parental education and household income) and depressed mood from age 13 to 40 with life transitions (leaving the parental home, leaving the educational system, beginning cohabitation, attaining employment) as pathways between the two. Our analyses were based on a 27-year longitudinal dataset (n = 1242) of a Norwegian cohort with 10 time points in total. To make socioeconomic comparisons, three groups (low, mid, and high) were made for parental education and income respectively.ResultsDepressed mood decreased from age 13 to 40. The low and high parental education groups showed a stable difference in depressed mood during early adolescence, which decreased in young adulthood and then increased slightly in mid-adulthood. The low household income group showed higher depressed mood across young adulthood compared to the medium and higher household income groups. For life transitions, leaving the parental home and beginning cohabitation was associated with an added downturn of the trajectory of depressed mood when adjusting for other transitions. However, adolescents with high parental education showed a relatively stronger decrease in depressed mood when leaving the parental home. Similarly, adolescents with a high household income showed a relatively stronger decrease in depressed mood when leaving the educational system.ConclusionsDepressed mood decreased over time and developed differently depending on parental education and household income. Life transitions were generally associated with reductions in depressed mood across time, but lower SES youths were not found to be more socially vulnerable these effects.

The role that inhaled particulate matter plays in the development of post-deployment lung disease among US service members deployed to Southwest Asia during the Global War on Terrorism has been difficult to define. There is a persistent gap in data addressing the relationship between relatively short-term (months to a few years) exposures to high levels of particulate matter during deployment and the subsequent development of adverse pulmonary outcomes. Surgical lung biopsies from deployed service members and veterans (DSMs) and non-deployed service members and veterans (NDSMs) who develop lung diseases can be analyzed to potentially identify residual deployment-specific particles and develop associations with pulmonary pathological diagnoses. We examined 52 surgical lung biopsies from 25 DSMs and 27 NDSMs using field emission scanning electron microscopy (FE-SEM) with energy dispersive x-ray spectroscopy (EDS) to identify any between-group differences in the number and composition of retained inorganic particles, then compared the particle analysis results with the original histopathologic diagnoses. We recorded a higher number of total particles in biopsies from DSMs than from NDSMs, and this difference was mainly accounted for by geologic clays (illite, kaolinite), feldspars, quartz/silica, and titanium-rich silicate mixtures. Biopsies from DSMs deployed to other Southwest Asia regions (SWA-Other) had higher particle counts than those from DSMs primarily deployed to Iraq or Afghanistan, due mainly to illite. Distinct deployment-specific particles were not identified. Particles did not qualitatively associate with country of deployment. The individual diagnoses of the DSMs and NDSMs were not associated with elevated levels of total particles, metals, cerium oxide, or titanium dioxide particles. These results support the examination of particle-related lung disease in DSMs in the context of comparison groups, such as NDSMs, to assist in determining the strength of associations between specific pulmonary pathology diagnoses and deployment-specific inorganic particulate matter exposure.

Summary: Zebrafish (Danio rerio) are increasingly used to investigate spine development, growth, and for studying the etiology of spinal deformity, such as scoliosis. Here, we present a micro-computed tomography-based pipeline for visualizing the zebrafish skeleton. We describe steps for sample preparation, imaging, data management, and processing. We then detail analysis of vertebral and spine morphology using open-source software. This protocol will be useful for scientists using zebrafish to understand spine development and disease.For complete details on the use and execution of this protocol, please refer to Bearce et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Melt rates at the base of Antarctic ice shelves are needed to drive projections of the Antarctic ice sheet mass loss. Current basal melt parameterizations struggle to link open ocean properties to ice‐shelf basal melt rates for the range of current sub‐shelf cavity geometries around Antarctica. We present a proof of concept exploring the potential of simple deep learning techniques to parameterize basal melt. We train a simple feedforward neural network, or multilayer perceptron, acting on each grid cell separately, to emulate the behavior of circum‐Antarctic cavity‐resolving ocean simulations. We find that this kind of emulator produces reasonable basal melt rates for our training ensemble, at least as close as or closer to the reference than traditional parameterizations. On an independent ensemble of simulations that was produced with the same ocean model but with different model parameters, cavity geometries and forcing, the neural network yields similar results to traditional parameterizations on present conditions. In much warmer conditions, both traditional parameterizations and neural network struggle, but the neural network tends to produce basal melt rates closer to the reference than a majority of traditional parameterizations. While this shows that such a neural network is at least as suitable for century‐scale Antarctic ice‐sheet projections as traditional parameterizations, it also highlights that tuning any parameterization on present‐like conditions can introduce biases and should be used with care. Nevertheless, this proof of concept is promising and provides a basis for further development of a deep learning basal melt parameterization.

Certain schools of phenomenological psychiatry conceive of schizophrenia as a pathology of common-sense. Ethnomethodological enquiry, with its roots in Schutzian social phenomenology, takes as its domain, topic, and substance of study the ongoing achievement of a common-sense world between social members. Yet, dialogue between psychiatry and ethnomethodological approaches is thin. In this article, we discuss a conversation analytic approach to schizophrenic interaction which has generated and utilized a model of a five-world manifold to frame analyses of talk-in-interaction. ‘Worlds’ are conceived, after Schutz, as finite domains of meaning, and the model operates as a breach of natural attitude assumptions to examine mechanisms of the constitution of the one-world-in-common of common-sense. It is suggested that certain aspects of schizophrenic talk might receive account in terms of a loss of integration between these five domains of meaning. Conversation Analytic methods were applied to transcripts of audio recordings of psychiatric interviews but encountered hurdles that motivated the broadening of methodological scope. Such hurdles included a weakening of the next turn proof procedure, implicit reification of the schizophrenia construct, and problems of translation presented by the analyst’s normative membership encountering non-normative life-worlds of schizophrenic experience. Strategic responses to these hurdles included exploring linkages between phenomenological psychiatry and ethnomethodological approaches, as well as an engagement of ethnomethodological self-reflection and conceptual clarification of the schizophrenia construct in line with Garfinkel’s unique adequacy requirement. The manifold model is glossed, and interaction between two of its worlds – a world of concrete, situational immediacies and another of abstract organizations – is explored in more detail via analysis of conversational data. It is suggested that the five-world model, along with further micro-analysis of talk-in-interaction, might have implications in psychiatry for topics such as autism, double bookkeeping, concretism, theories of disturbed indexicality, and insight attribution. We conclude that the consideration of atypical interaction obliges the interaction analyst to take account of their own implicit normative world-frames and that the use of domain-specific top-down models in conjunction with the inductive approach of Conversation Analysis may extend the reach of CA to facilitate productive dialogue with other disciplines.

ABSTRACTNucleic acid vaccines are designed based on genetic sequences (DNA or mRNA) of a target antigen to be expressed in vivo to drive a host immune response. In response to the COVID-19 pandemic, mRNA and DNA vaccines based on the SARS-CoV-2 Spike antigen were developed. Surprisingly, head-to-head characterizations of the immune responses elicited by each vaccine type has not been performed to date. Here, we have employed a range of preclinical animal models including the hamster, guinea pig, rabbit, and mouse to compare and delineate the immune response raised by DNA, administered intradermally (ID) with electroporation (EP) and mRNA vaccines (BNT162b2 or mRNA-1273), administered intramuscularly (IM), expressing the SARS-CoV-2 WT spike antigen. The results revealed clear differences in the quality and magnitude of the immune response between the two vaccine platforms. The DNA vaccine immune response was characterized by strong T cell responses, while the mRNA vaccine elicited robust humoral responses. The results may assist in guiding the disease target each vaccine type may be best matched against and suggest mechanisms to further enhance the breadth of each platform’s immune response.

Abstract Background Therapy dropout poses a major challenge. Considerable research has been conducted on predictors of dropout, however none in the context of primary mental health services in Norway. The purpose of this study was to investigate which client characteristics can predict dropout from the service Prompt Mental Health Care (PMHC). Methods We performed a secondary analysis of a Randomized Controlled Trial (RCT). Our sample consisted of 526 adult participants receiving PMHC-treatment in the municipalities of Sandnes and Kristiansand, between November 2015 to August 2017. Using logistic regression, we investigated the association between nine client characteristics and dropout. Results The dropout rate was 25.3%. The adjusted analysis indicated that older clients had a lower odds ratio (OR) of dropping out compared to younger clients (OR = 0.43, [95% CI = 0.26, 0.71]). Moreover, clients with higher education had a lower odds ratio of dropping out compared to clients with lower levels of education (OR = 00.55, 95% CI [0.34, 0.88]), while clients who were unemployed were more likely to drop-out as compared the regularly employed (OR = 2.30, [95% CI = 1.18, 4.48]). Finally, clients experiencing poor social support had a higher odds ratio of dropping out compared to clients who reported good social support (OR = 1.81, [95% CI = 1.14, 2.87]). Sex, immigrant background, daily functioning, symptom severity and duration of problems did not predict dropout. Conclusion The predictors found in this prospective study might help PMHC-therapists identify clients at risk of dropout. Strategies for preventing dropout are discussed.

Abstract Background Marital status is a robust correlate of disordered gambling, but few studies have examined the direction of this association. Methods The present study used a case–control design by including all adults receiving their first gambling disorder (GD) diagnosis between January 2008 to December 2018 (Norwegian Patient Registry, n = 5,121) and compared them against age and gender matched individuals with other somatic/psychiatric illnesses (Norwegian Patient Registry, n = 27,826) and a random sample from the general population (FD-Trygd database, n = 26,695). The study examined marital status before GD, getting divorced as a risk factor for future GD, and becoming married as a protective factor of future GD. Results The findings indicated an 8–9 percentage points higher prevalence of unmarried people and about a 5 percentage points higher prevalence of separation/divorce among those that subsequently experienced GD compared to controls. Logistic regressions showed that transition through divorce was associated with higher odds of future GD compared to illness controls (odds ratio [OR] = 2.89, 95% CI [2.41, 3.45]) and the general population (OR = 2.83 [2.36, 3.38]). Logistic regressions also showed that transition through marriage was associated with lower odds of future GD compared to illness controls (OR = 0.62, CI [0.55, 0.70]) and the general population (OR = 0.57, CI [0.50, 0.64]). Conclusions Social bonds have previously been shown to impact physical and mental health, and the findings of the study emphasize the importance of considering social network history and previous relationship dissolution among individuals with GD.

Abstract Background Outcomes following aortic occlusion for trauma and hemorrhagic shock are poor, leading some to question the clinical utility of aortic occlusion in this setting. This study evaluates neurologically intact survival following resuscitative endovascular balloon occlusion of the aorta (REBOA) versus resuscitative thoracotomy at a center with a dedicated trauma hybrid operating room with angiographic capabilities. Methods This retrospective cohort analysis compared patients who underwent zone 1 aortic occlusion via resuscitative thoracotomy (n = 13) versus REBOA (n = 13) for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock (systolic blood pressure less than 90 mmHg despite volume resuscitation) at a level 1 trauma center with a dedicated trauma hybrid operating room. The primary outcome was survival to hospital discharge. The secondary outcome was neurologic status at hospital discharge, assessed by Glasgow Coma Scale (GCS) scores. Results Overall median age was 40 years, 27% had penetrating injuries, and 23% had pre-hospital closed-chest cardiopulmonary resuscitation. In both cohorts, median injury severity scores and head-abbreviated injury scores were 26 and 2, respectively. The resuscitative thoracotomy cohort had lower systolic blood pressure on arrival (0 [0–75] vs. 76 [65–99], p = 0.009). Hemorrhage control (systolic blood pressure 100 mmHg without ongoing vasopressor or transfusion requirements) was obtained in 77% of all REBOA cases and 8% of all resuscitative thoracotomy cases (p = 0.001). Survival to hospital discharge was greater in the REBOA cohort (54% vs. 8%, p = 0.030), as was discharge with GCS 15 (46% vs. 0%, p = 0.015). Conclusions Among patients undergoing aortic occlusion for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock at a center with a dedicated, trauma hybrid operating room, nearly half of all patients managed with REBOA had neurologically intact survival. The high death rate in resuscitative thoracotomy and differences in patient cohorts limit direct comparison.

According to relativity, the reading of an ideal clock is interpreted as the elapsed proper time along its classical trajectory through spacetime. In contrast, quantum theory allows the association of many simultaneous trajectories with a single quantum clock, each weighted appropriately. Here, we investigate how the superposition principle affects the gravitational time dilation observed by a simple clock – a decaying two-level atom. Placing such an atom in a superposition of positions enables us to analyze a quantum contribution to a classical time dilation manifest in spontaneous emission. In particular, we show that the emission rate of an atom prepared in a coherent superposition of separated wave packets in a gravitational field is different from the emission rate of an atom in a classical mixture of these packets, which gives rise to a quantum gravitational time dilation effect. We demonstrate that this nonclassical effect also manifests in a fractional frequency shift of the internal energy of the atom that is within the resolution of current atomic clocks. In addition, we show the effect of spatial coherence on the atom's emission spectrum.

The collapse of antiferromagnetic order as a function of some quantum tuning parameter such as carrier density or hydrostatic pressure is often accompanied by a region of superconductivity. The corresponding phenomenon in the potentially simpler case of itinerant-electron ferromagnetism, however, remains more illusive. In this paper we consider the reasons why this may be so and summaries evidence suggesting that the obstacles to observing the phenomenon are apparently overcome in a few metallic ferromagnets. A new twist to the problem presented by the recent discoveries in ferroelectric symmetric systems and new graphite intercalate superconductors will also be discussed.

IntroductionAllergic reactions are mediated by human IgE antibodies that bind to and cross-link allergen molecules. The sites on allergens that are recognized by IgE antibodies have been difficult to investigate because of the paucity of IgE antibodies in a human serum. Here, we report the production of unique human IgE monoclonal antibodies to major inhaled allergens and food allergens that can be produced at scale in perpetuity.Materials and methodsThe IgE antibodies were derived from peripheral blood mononuclear cells of symptomatic allergic patients, mostly children aged 3–18 years, using hybridoma fusion technology. Total IgE and allergen-specific IgE was measured by ImmunoCAP. Their specificity was confirmed through ELISA and immunoblotting. Allergenic potency measurements were determined by ImmunoCAP inhibition. Biological activity was determined in vitro by comparing β-hexosaminidase release from a humanized rat basophilic cell line.ResultsHuman IgE monoclonal antibodies (n = 33) were derived from 17 allergic patients with symptoms of allergic rhinitis, asthma, atopic dermatitis, food allergy, eosinophilic esophagitis, or red meat allergy. The antibodies were specific for five inhaled allergens, nine food allergens, and alpha-gal and had high levels of IgE (53,450–1,702,500 kU/L) with ratios of specific IgE to total IgE ranging from

BackgroundExercise can improve cognition in aging, however it is unclear how exercise influences cognition, and sleep may partially explain this association. The current study aimed to investigate whether objectively measured sleep mediates the effect of an acute exercise intervention on cognition in older adults.MethodsParticipants were 30 cognitively unimpaired, physically active older adults (69.2 ± 4.3 years) with poor sleep (determined via self-report). After a triple baseline cognitive assessment to account for any natural fluctuation in cognitive performance, participants completed either a single bout of 20-minutes of high intensity exercise on a cycle ergometer, or a control condition, in a cross-over trial design. Cognition was measured immediately post-intervention and the following day, and sleep (total sleep time, sleep onset latency, sleep efficiency, % of rapid eye movement sleep, light sleep and deep sleep) was characterized using WatchPAT™ at baseline (5 nights) and measured for one night after both exercise and control conditions.ResultsResults showed no effect of the exercise intervention on cognition immediately post-intervention, nor an effect of acute exercise on any sleep variable. There was no mediating effect of sleep on associations between exercise and cognition. However, a change from baseline to post-intervention in light sleep and deep sleep did predict change in episodic memory at the ~24 h post-intervention cognitive assessment, regardless of intervention condition.DiscussionThere was no effect of acute high intensity exercise on sleep or cognition in the current study. However, results suggest that associations between sleep and cognition may exist independently of exercise in our sample. Further research is required, and such studies may aid in informing the most effective lifestyle interventions for cognitive health.

Abstract Giant icebergs release cold, fresh meltwater as they drift, perturbing the physical conditions of the surface ocean. This study uses satellite‐derived sea surface salinity and temperature measurements to explore the physical impact of supergiant iceberg A68A between September 2020 and June 2021. During A68A's drift through the Scotia Sea in austral spring, gradual but persistent edge‐wasting contributed to a freshening of several psu extending hundreds of kilometers ahead of the iceberg, whilst the cooling signal was more pronounced in the iceberg's wake. The magnitude of the physical perturbation intensified during A68A's breakup near South Georgia. Several large meltwater lenses surrounding the descendant icebergs displayed temperature anomalies of up to −4.5°C, whilst the salinity measurements indicated a surface (skin‐depth) anomaly regularly exceeding order −10 psu. The perturbations stretched at times >1,000 km and persisted for >2 months following A68A's melt in April 2021.

Abstract Pelvic organ prolapse, urinary, bowel and sexual dysfunction, collectively called pelvic floor dysfunction (PFD) affects 1 in 3 women and has a significant public health impact. The causes of PFD are not fully understood but involve injury to connective tissue and motor nerve during childbirth. Women with PFD also have sensory nerve impairment, and it is likely this occurs during childbirth, but this has never been investigated. In the current study 150 women underwent quantitative sensory testing for vibration sensation at the vagina and clitoris, and stretch sensation at the vagina and introitus, in the third trimester, 3 and 6 months postnatal. Antenatally vibration sensation was reduced but stretch sensation was normal. Postnatally vibration sensation deteriorated whilst stretch sensation initially deteriorated but recovered by 6 months postnatal to antenatal levels (all p

Abstract The ongoing COVID-19 pandemic is among the worst in recent history, resulting in excess of 520,000,000 cases and 6,200,000 deaths worldwide. The United States (U.S.) has recently surpassed 1,000,000 deaths. Individuals who are elderly and/or immunocompromised are the most susceptible to serious sequelae. Rising sentiment often implicates younger, less-vulnerable populations as primary introducers of COVID-19 to communities, particularly around colleges and universities. Adjusting for more than 32 key socio-demographic, economic, and epidemiologic variables, we (1) implemented regressions to determine the overall community-level, age-adjusted COVID-19 case and mortality rate within each American county, and (2) performed a subgroup analysis among a sample of U.S. colleges and universities to identify any significant preliminary mitigation measures implemented during the fall 2020 semester. From January 1, 2020 through March 31, 2021, a total of 22,385,335 cases and 374,130 deaths were reported to the CDC. Overall, counties with increasing numbers of university enrollment showed significantly lower case rates and marginal decreases in mortality rates. County-level population demographics, and not university level mitigation measures, were the most significant predictor of adjusted COVID-19 case rates. Contrary to common sentiment, our findings demonstrate that counties with high university enrollments may be more adherent to public safety measures and vaccinations, likely contributing to safer communities.

Here we present the first open-access long-term 3D hydrodynamic ocean hindcast for the New Zealand ocean estate. The 28-year 5 km×5 km resolution free-running ocean model configuration was developed under the umbrella of the Moana Project, using the Regional Ocean Modeling System (ROMS) version 3.9. It includes an improved bathymetry, spectral tidal forcing at the boundaries and inverse-barometer effect usually absent from global simulations. The continuous integration provides a framework to improve our understanding of the ocean dynamics and connectivity, as well as identify long-term trends and drivers for particular processes. The simulation was compared to a series of satellite and in situ observations, including sea surface temperature (SST), sea surface height (SSH), coastal water level and temperature stations, moored temperature time series, and temperature and salinity profiles from the CORA5.2 (Coriolis Ocean database for ReAnalysis) dataset – including Argo floats, XBTs (expendable bathythermographs) and CTD (conductivity–temperature–depth) stations. These comparisons show the model simulation is consistent and represents important ocean processes at different temporal and spatial scales, from local to regional and from a few hours to years including extreme events. The root mean square errors are 0.11 m for SSH, 0.23 ∘C for SST, and ∘C and 0.15 g kg−1 for temperature and salinity profiles. Coastal tides are simulated well, and both high skill and correlation are found between modelled and observed sub-tidal sea level and water temperature stations. Moreover, cross-sections of the main currents around New Zealand show the simulation is consistent with transport, velocity structure and variability reported in the available literature. This first multi-decadal, high-resolution, open-access hydrodynamic model represents a significant step forward for ocean sciences in the New Zealand region.

The Antarctic Ice Sheet will play a crucial role in the evolution of global mean sea level as the climate warms. An interactively coupled climate and ice sheet model is needed to understand the impacts of ice–climate feedbacks during this evolution. Here we use a two-way coupling between the UK Earth System Model and the BISICLES (Berkeley Ice Sheet Initiative for Climate at Extreme Scales) dynamic ice sheet model to investigate Antarctic ice–climate interactions under two climate change scenarios. We perform ensembles of SSP1–1.9 and SSP5–8.5 (Shared Socioeconomic Pathway) scenario simulations to 2100, which we believe are the first such simulations with a climate model that include two-way coupling of atmosphere and ocean models to dynamic models of the Greenland and Antarctic ice sheets. We focus our analysis on the latter. In SSP1–1.9 simulations, ice shelf basal melting and grounded ice mass loss from the Antarctic Ice Sheet are generally lower than present rates during the entire simulation period. In contrast, the responses to SSP5–8.5 forcing are strong. By the end of the 21st century, these simulations feature order-of-magnitude increases in basal melting of the Ross and Filchner–Ronne ice shelves, caused by intrusions of masses of warm ocean water. Due to the slow response of ice sheet drawdown, this strong melting does not cause a substantial increase in ice discharge during the simulations. The surface mass balance in SSP5–8.5 simulations shows a pattern of strong decrease on ice shelves, caused by increased melting, and strong increase on grounded ice, caused by increased snowfall. Despite strong surface and basal melting of the ice shelves, increased snowfall dominates the mass budget of the grounded ice, leading to an ensemble mean Antarctic contribution to global mean sea level of a fall of 22 mm by 2100 in the SSP5–8.5 scenario. We hypothesise that this signal would revert to sea-level rise on longer timescales, caused by the ice sheet dynamic response to ice shelf thinning. These results demonstrate the need for fully coupled ice–climate models in reducing the substantial uncertainty in sea-level rise from the Antarctic Ice Sheet.

Here, Parzych et al describe the development of a DNA-delivered SARS-CoV-2 mAb cocktail displaying synergistic RBD binding that confers broad neutralizing activity against variants of concern and prophylactic efficacy in multiple small animal models.

BackgroundCirculation of multidrug-resistant bacteria (MRB) in healthcare facilities is a major public health problem. These settings have been greatly impacted by the Coronavirus Disease 2019 (COVID-19) pandemic, notably due to surges in COVID-19 caseloads and the implementation of infection control measures. We sought to evaluate how such collateral impacts of COVID-19 impacted the nosocomial spread of MRB in an early pandemic context.Methods and findingsWe developed a mathematical model in which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and MRB cocirculate among patients and staff in a theoretical hospital population. Responses to COVID-19 were captured mechanistically via a range of parameters that reflect impacts of SARS-CoV-2 outbreaks on factors relevant for pathogen transmission. COVID-19 responses include both "policy responses" willingly enacted to limit SARS-CoV-2 transmission (e.g., universal masking, patient lockdown, and reinforced hand hygiene) and "caseload responses" unwillingly resulting from surges in COVID-19 caseloads (e.g., abandonment of antibiotic stewardship, disorganization of infection control programmes, and extended length of stay for COVID-19 patients). We conducted 2 main sets of model simulations, in which we quantified impacts of SARS-CoV-2 outbreaks on MRB colonization incidence and antibiotic resistance rates (the share of colonization due to antibiotic-resistant versus antibiotic-sensitive strains). The first set of simulations represents diverse MRB and nosocomial environments, accounting for high levels of heterogeneity across bacterial parameters (e.g., rates of transmission, antibiotic sensitivity, and colonization prevalence among newly admitted patients) and hospital parameters (e.g., rates of interindividual contact, antibiotic exposure, and patient admission/discharge). On average, COVID-19 control policies coincided with MRB prevention, including 28.2% [95% uncertainty interval: 2.5%, 60.2%] fewer incident cases of patient MRB colonization. Conversely, surges in COVID-19 caseloads favoured MRB transmission, resulting in a 13.8% [-3.5%, 77.0%] increase in colonization incidence and a 10.4% [0.2%, 46.9%] increase in antibiotic resistance rates in the absence of concomitant COVID-19 control policies. When COVID-19 policy responses and caseload responses were combined, MRB colonization incidence decreased by 24.2% [-7.8%, 59.3%], while resistance rates increased by 2.9% [-5.4%, 23.2%]. Impacts of COVID-19 responses varied across patients and staff and their respective routes of pathogen acquisition. The second set of simulations was tailored to specific hospital wards and nosocomial bacteria (methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli). Consequences of nosocomial SARS-CoV-2 outbreaks were found to be highly context specific, with impacts depending on the specific ward and bacteria evaluated. In particular, SARS-CoV-2 outbreaks significantly impacted patient MRB colonization only in settings with high underlying risk of bacterial transmission. Yet across settings and species, antibiotic resistance burden was reduced in facilities with timelier implementation of effective COVID-19 control policies.ConclusionsOur model suggests that surges in nosocomial SARS-CoV-2 transmission generate selection for the spread of antibiotic-resistant bacteria. Timely implementation of efficient COVID-19 control measures thus has 2-fold benefits, preventing the transmission of both SARS-CoV-2 and MRB, and highlighting antibiotic resistance control as a collateral benefit of pandemic preparedness.

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (Aβ) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer’s disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of Aβ, the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut–brain axis (GBA) in the context of AD progression and pathology have yielded inconsistent findings. This review aims to enhance our understanding of microbial diversity at the species level and the role of these species in AD pathology. Additionally, this review addresses the influence of confounding elements, including diet, probiotics, and prebiotics, on AD throughout different stages (preclinical, mild cognitive impairment (MCI), and AD) of its progression.

Abstract Objectives The purpose of this study is to provide expert consensus recommendations to establish a global ultrasound curriculum for undergraduate medical students. Methods 64 multi-disciplinary ultrasound experts from 16 countries, 50 multi-disciplinary ultrasound consultants, and 21 medical students and residents contributed to these recommendations. A modified Delphi consensus method was used that included a systematic literature search, evaluation of the quality of literature by the GRADE system, and the RAND appropriateness method for panel judgment and consensus decisions. The process included four in-person international discussion sessions and two rounds of online voting. Results A total of 332 consensus conference statements in four curricular domains were considered: (1) curricular scope (4 statements), (2) curricular rationale (10 statements), (3) curricular characteristics (14 statements), and (4) curricular content (304 statements). Of these 332 statements, 145 were recommended, 126 were strongly recommended, and 61 were not recommended. Important aspects of an undergraduate ultrasound curriculum identified include curricular integration across the basic and clinical sciences and a competency and entrustable professional activity-based model. The curriculum should form the foundation of a life-long continuum of ultrasound education that prepares students for advanced training and patient care. In addition, the curriculum should complement and support the medical school curriculum as a whole with enhanced understanding of anatomy, physiology, pathophysiological processes and clinical practice without displacing other important undergraduate learning. The content of the curriculum should be appropriate for the medical student level of training, evidence and expert opinion based, and include ongoing collaborative research and development to ensure optimum educational value and patient care. Conclusions The international consensus conference has provided the first comprehensive document of recommendations for a basic ultrasound curriculum. The document reflects the opinion of a diverse and representative group of international expert ultrasound practitioners, educators, and learners. These recommendations can standardize undergraduate medical student ultrasound education while serving as a basis for additional research in medical education and the application of ultrasound in clinical practice.

BackgroundHuman Immunoglobulin E monoclonal antibodies (hIgE mAb) are unique tools for investigating IgE responses. Here, the biological activity of hIgE mAb, derived from immortalized B cells harvested from the blood of allergic donors, targeting three allergens (Der p 2, Fel d 1 and Ara h 2) was investigated.MethodsThree Der p 2-, three Fel d 1- and five Ara h 2-specific hIgE mAb produced by human B cell hybridomas, were combined in pairs and used to passively sensitize humanized rat basophilic leukemia cells and compared with sensitization using serum pools. Sensitized cells were stimulated with corresponding allergens (recombinant or purified), allergen extracts or structural homologs, having 40-88% sequence similarity, and compared for mediator (β-hexosaminidase) release.ResultsOne, two and eight pairs of Der p 2-, Fel d 1- and Ara h 2-specific hIgE mAb, respectively, produced significant mediator release (>50%). A minimum hIgE mAb concentration of 15-30 kU/L and a minimum antigen concentration between 0.01-0.1 µg/mL were sufficient to induce a pronounced mediator release. Individual sensitization with one Ara h 2-specific hIgE mAb was able to induce crosslinking independently of a second specific hIgE mAb. Der p 2- and Ara h 2-specific mAb showed a high allergen specificity when compared to homologs. Mediator release from cells sensitized with hIgE mAb was comparable to serum sensitization.ConclusionThe biological activity of hIgE mAb reported here provides the foundation for novel methods of standardization and quality control of allergen products and for mechanistic studies of IgE-mediated allergic diseases, using hIgE mAb.

IntroductionCyberbullying, or repeatedly communicating antagonistic messages using digital or electronic media meant to deal out harm or discomfort to others, has been considered more pervasive and impactful than traditional bullying since perpetrators can remain anonymous online, are not bound by time or place. In addition, cyberbullied youth are reluctant to involve others such as an adult or confront the perpetrator adults. Therefore, the primary purpose of this study was to capture a holistic understanding of potential youth cyberbullying prevention and intervention strategies (i.e., inhibiting forces that may reduce cyberbullying) from key stakeholders with professional knowledge about cyberbullying (i.e., educational administration, psychological counseling, technology and bullying education consultation, policing, research, and social support services).MethodsTwenty (n = 20) participants were recruited using purposive and snowball sampling techniques from both urban and rural school districts in one Western Canadian province to participate in either in a semi-structured individual interview (n = 16) or a scheduled focus group (n = 4) to achieve depth and understanding of cyberbullying issues. The I3 Model, a process-oriented metatheory of aggression with the potential to explain how cyberbullying behaviors continue to occur, was used as a frame to analyze the qualitatively gathered data using six phases of reflexive thematic analysis.ResultsParticipants identified educational efforts related to awareness of cyberbullying and consequences of perpetration, digital citizenship programming for students and social skills training, providing remediation to youth who are in online conflict with one another, and parental engagement with the technology used by their youth as key factors in mitigating instances of cyberbullying.DiscussionThis study furthers research on cyberbullying prevention and intervention in schools by illuminating experiences from under researched and unique stakeholders in the field. These key findings and suggestions for future research are further discussed.

Using ramp compression, silicon carbide was compressed to pressures of 1.5 terapascals, more than seven times higher than previous work. The results show that large carbon-rich exoplanets would be ~10% less dense than corresponding rocky planets.

The high-pressure (HP) behavior of dioxides is of interest due to their extensive polymorphism and role as analogs for SiO_{2}, a phase expected to be important in the deep mantles of Earth and terrestrial exoplanets. Here we report on dynamic ramp compression of quartz-type germanium dioxide GeO_{2} to stresses up to 882 GPa, a higher peak stress than previous studies by a factor of 5. X-ray diffraction data show that HP-PdF_{2}-type GeO_{2} occurs under ramp loading from 154 to 440 GPa, and this phase persists to higher pressure than predicted by theory. Above 440 GPa, we observe evidence for transformation to a new phase of GeO_{2}. Based on the diffraction data, the best candidate for this new phase is the cotunnite-type structure which has been predicted to be a stable phase of GeO_{2} above 300 GPa. The HP-PdF_{2}-type and cotunnite-type structures are important phases in a wide range of AX_{2} compounds, including SiO_{2}, at multihundred GPa stresses. Our results demonstrate that ramp compression can be an effective technique for synthesizing and characterizing such phases in oxides. In addition, we show that pulsed x-ray diffraction under ramp compression can be used to examine lower-symmetry phases in oxide materials.

Cancer immunotherapy has demonstrated great promise with several checkpoint inhibitors being approved as the first-line therapy for some types of cancer, and new engineered cytokines such as Neo2/15 now being evaluated in many studies. In this work, we designed antibody-cytokine chimera (ACC) scaffolding cytokine mimetics on a full-length tumor-specific antibody. We characterized the pharmacokinetic (PK) and pharmacodynamic (PD) properties of first-generation ACC TA99-Neo2/15, which synergized with DLnano-vaccines to suppress in vivo melanoma proliferation and induced significant systemic cytokine activation. A novel second-generation ACC TA99-HL2-KOA1, with retained IL-2Rβ/γ binding and attenuated but preserved IL-2Rα binding, induced lower systemic cytokine activation with non-inferior protection in murine tumor studies. Transcriptomic analyses demonstrated an upregulation of Type I interferon responsive genes, particularly ISG15, in dendritic cells, macrophages and monocytes following TA99-HL2-KOA1 treatment. Characterization of additional ACCs in combination with cancer vaccines will likely be an important area of research for treating melanoma and other types of cancer.