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In service of the goal of examining how cognitive science can facilitate human-computer interactions in complex systems, we explore how cognitive psychology research might help educators better utilize artificial intelligence and AI supported tools as facilitatory to learning, rather than see these emerging technologies as a threat. We also aim to provide historical perspective, both on how automation and technology has generated unnecessary apprehension over time, and how generative AI technologies such as ChatGPT are a product of the discipline of cognitive science. We introduce a model for how higher education instruction can adapt to the age of AI by fully capitalizing on the role that metacognition knowledge and skills play in determining learning effectiveness. Finally, we urge educators to consider how AI can be seen as a critical collaborator to be utilized in our efforts to educate around the critical workforce skills of effective communication and collaboration.

Objective: To summarize the prevalence of Long COVID symptoms among the general population reported in published articles from the pre-omicron SARS-CoV2 era. This narrative review examined 21 symptoms. Methods: A PubMed/manual search returned 114 articles on general Long COVID symptoms. Manuscripts were excluded if they were not research studies, did not report symptom prevalence, or used a pediatric population. Ninety-eight studies were selected for review and fifty-nine met the criteria for inclusion. The risk of bias was assessed with the Hoy critical appraisal tool. Results: After excluding studies with a high risk of bias, meta-analysis of prevalence for 21 symptom categories ranged from 2.6–28.7% in studies based on surveys to 0.3–7.1% in studies based on electronic health record data. Conclusions: Long COVID symptom studies are limited by the variability in study design and representation of the general population. Further research is needed to effectively cluster symptoms in meaningful ways that enable focused treatment.

Abstract As of 2023, the use of prescribed fire to manage ecosystems accounts for more than 50% of area burned annually across the United States. Prescribed fire is carried out when meteorological conditions, including temperature, humidity, and wind speed are appropriate for its safe and effective application. However, changes in these meteorological variables associated with future climate change may impact future opportunities to conduct prescribed fire. In this study, we combine climate projections with information on prescribed burning windows for ecoregions across the contiguous United States (CONUS) to compute the number of days when meteorological conditions allow for the safe and effective application of prescribed fire under present-day (2006–2015) and future climate (2051–2060) conditions. The resulting projections, which cover 57% of all vegetated area across the CONUS, indicate fewer days with conditions suitable for prescribed burning across ecoregions of the eastern United States due to rising maximum daily temperatures, but opportunities increase in the northern and northwestern United States, driven primarily by rising minimum temperatures and declining wind speeds.

Abstract Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the genetic architecture and molecular pathogenesis of HC. Without this knowledge, the development of preventive, diagnostic, and therapeutic measures is impeded. However, the genetics of HC is extraordinarily complex, based on studies of varying size, scope, and rigor. This review serves to provide a comprehensive overview of genes, pathways, mechanisms, and global impact of genetics contributing to all etiologies of HC in humans.

Recent emphasis on market-based mechanisms as the key to solving sustainability challenges has left scholars and activists wringing their hands. This frustration and sense of urgency has been particularly poignant in the issues surrounding food production and land-use change. While creative approaches to promoting sustainable land-uses have abounded, intensive agricultural systems persist as a major cause of biodiversity loss. Mounting evidence indicates that a business-as-usual approach to encouraging sustainable food production rests on erroneous assumptions about human value systems and their link to food and land, often resulting in perverse and/or inadequate outcomes. The relational turn arrives onto this scene, revisiting central questions about how values inform action and how policy can leverage values for more sustainable and equitable solutions. We contribute to this discussion through sharing case studies of grassroots sustainable agricultural movements in Latin America. In each, we explore how relational values are linked to transformative action, and how this intersects with or challenges relevant institutions and political structures. Through this analysis, we illustrate the presence of the relational turn within these movements, while questioning whether existing institutions are prepared to embrace a relational approach to policy and norms. Instead, we suggest that the relational turn calls for a more radical transformation of existing institutions than that embraced by most policy makers, and that this central challenge will persist in any attempt to scale up sustainable ‘local’ movements to affect global change.

Abstract The OPRM1 gene codes for the mu opioid receptor (MOR) and polymorphisms are associated with complex patient clinical responses. The most studied single nucleotide polymorphism (SNP) in OPRM1 is adenine (A) substituted by guanine (G) at position 118 (118A>G, rs1799971) leading to a substitution of asparagine (Asn) for aspartic acid (Asp) at position 40 in the N terminus of the resulting protein. To date, no structural explanation for the associated clinical responses resulting from the 118A>G polymorphism has been proposed. We utilized computational modeling paired with functional cellular assays to predict unstructured N‐ and C‐terminal regions of MOR‐1. Using molecular docking and post‐docking energy minimizations with morphine, we show that the extracellular substitution of Asn at position 40 alters the cytoplasmic C‐terminal conformation, while leaving the G‐protein binding interface unaffected. A real‐time BRET assay measuring G‐protein and β‐arrestin association with MOR r generated data that tested this prediction. Consistent with this in silico prediction, we show changes in morphine‐mediated β‐arrestin association with receptor variants with little change in morphine‐mediated G‐protein association comparing MOR‐1 wild type (WT) to MOR‐1118A>G. We tested the system with different opioid agonists, the OPRM1 118A>G SNP, and different MOR splice variants (MOR‐1 and MOR‐1O). These results are consistent with the observation that patients with the 118A>G OPRM1 allele respond more readily to fentanyl than to morphine. In conclusion, the 118A>G substitution alters receptor responses to opioids through variable C‐terminal domain movements that are agonist and splice variant dependent.

The Devonian-Carboniferous (D-C; 359 Ma) boundary is marked by widespread deposition of organic-matter-rich black shales associated with the Hangenberg mass extinction event. The Exshaw Formation spans the D-C boundary in the Western Canada Sedimentary Basin (WCSB) and includes the basal Exshaw Shale deposited under broadly anoxic waters. The sediments at the base of the Exshaw Shale were deposited synchronously during a transgressive event across the WCSB, spanning the geographic variability of the basin. The variable Corg content of the shale was affected by local nutrient upwelling and paleotectonic features impacting water depth and circulation. To characterize the link between paleogeography and nutrient cycling, geographic (N = 20 locations) and stratigraphic (N = 6 locations) trends of δ13Corg and δ15Nbulk were examined throughout the WCSB, representing a range of depositional settings. The δ15Nbulk values range between 0.0 and 6.3‰ and δ13Corg from −29.5 to −26.8‰. Phytoplankton production in focused upwelling zones acquired a relatively 15N-depleted signature through isotopic fractionation during nutrient assimilation, and the residual nutrient pool was 15N-enriched. The advection of surface waters away from the location of upwelling supported additional phytoplankton growth and the deposition of sediments with higher δ15N values. The stratigraphic sections include black laminated and burrowed mudrock sequences that record changes in paleoredox conditions, water depth, and tectonism over time. Up-core from the base of the Exshaw, the Corg content decreases and simultaneously δ15Nbulk increases, suggesting a decrease in eutrophic conditions. Variable δ13Corg and δ15Nbulk trends demonstrate that there is no “type” isotopic profile spanning the D-C boundary in the WCSB.

Introduction: There remains a paucity of literature examining the decision algorithm for use of nasoseptal flap (NSF) after endoscopic endonasal approaches (EEA) to pituitary adenoma resection. In 2018, we published the first ever flap risk score (FRS) to predict the use of NSF. We present here a validity study examining the FRS as applied to our center. Methods: A retrospective review was completed of consecutive patients undergoing EEA from January 2015 to March 2021. The sensitivity, specificity, and predictive value of the FRS were calculated. A multivariate logistic model was used to determine the relative weight imaging characteristics in predicting need for NSF. The relative weighting of the FRS was then re-optimized. Results: A total of 376 patients underwent EEA for pituitary adenoma resection, with 113 (30.1%) requiring NSF. The FRS had a sensitivity and specificity of 43.4% and 94.7%, respectively. Sphenoid sinus extension increased the odds of needing a NSF equivalent to 19 mm of tumor height, as opposed to 6 mm in the original 2018 cohort. The re-optimized model had sensitivity and specificity of 79.6% and 76.4%, respectively. Conclusion: We present a validity study examining the utility of FRS in predicting the use of NSF after EEA for pituitary adenoma resection. Our results show that while FRS is still predictive of the need for NSF after EEA, it is not as predictive now as it was for its original cohort. Therefore, a more comprehensive model is necessary to more accurately stratify patients’ preoperative risk for NSF.

The discovery of novel probiotic bacteria from free-ranging animals for the treatment of inflammatory bowel disease in domestic pets is a unique approach. The chloroform extraction of gastrointestinal (GI) tract material was used to inactivate vegetative cells and select for spore-forming bacteria. A bacterium identified as a novel Paenibacillus sp. strain via small ribosomal RNA (16S) gene sequencing was isolated from the GI tract of a gray wolf (Canis lupus). The bacterium was typed as Gram-variable, both catalase/oxidase-positive and positive via starch hydrolysis and lipase assays. The bacterium inhibited the growth of Staphylococcus aureus, Escherichia coli and Micrococcus luteus. The draft whole genome sequence (WGS) assembly was 7,034,206 bp in length, encoding 6543 genes, and is similar in size and coding capacity to other closely related Paenibacillus spp. The isolate’s genome encodes several germination and sporulation gene products along with antimicrobials such as a bacteriocin system and chitinase. Enzyme genes such as alpha amylase, cellulase, lipases and pectin lyase are also present in the genome. An incomplete lysogenic bacteriophage genome was also present in the isolate’s genome. Phenotypic characteristics combined with a WGS genotype analysis indicate that this bacterium, designated Paenibacillus sp. ClWae2A, could be a potential candidate probiotic for domestic dogs.

Background: The COVID-19 pandemic has had a severe impact on the Latin American subcontinent, particularly in areas with limited hospital resources and a restricted Intensive Care Unit (ICU) capacity. This study aimed to provide a comprehensive description of the clinical characteristics, outcomes, and factors associated with survival of COVID-19 hospitalized patients in Honduras. Research question: What were the characteristics and outcomes of COVID-19 patients in a large referral center in Honduras? Study design and methods: This study employed a retrospective cohort design conducted in a single center in San Pedro Sula, Honduras, between October 2020 to March 2021. All hospitalized cases of confirmed COVID-19 during this timeframe were included in the analysis. Univariable and multivariable survival analysis were performed using Kaplan-Meier curves and Cox proportional hazards model aiming to identify factors associated with decreased 30 day in-hospital survival, using a priori-selected factors. Results: A total of 929 confirmed cases were identified in this cohort, with males accounting for 55.4 % of cases. The case fatality rate among the hospitalized patients was found to be 50.1 % corresponding to 466 deaths. Patients with comorbidities such as hypertension, diabetes, obesity, chronic kidney disease, chronic obstructive pulmonary disease and cardiovascular disease had a higher likelihood of mortality. Additionally, non-survivors had a significantly longer time from illness onset to hospital admission compared to survivors (8.2 days vs 4.7 days). Among the cohort, 306 patients (32.9 %) met criteria for ICU admission. However, due to limited capacity, only 60 patients (19·6 %) were admitted to the ICU. Importantly, patients that were unable to receive level-appropriate care had lower likelihood of survival compared to those who received level-appropriate care (hazard ratio: 1.84). Interpretation: This study represents, the largest investigation of in-hospital COVID-19 cases in Honduras and Central America. The findings highlight a substantial case fatality rate among hospitalized patients. In this study, patients who couldn't receive level-appropriate care (ICU admission) had a significantly lower likelihood of survival when compared to those who did. These results underscore the significant impact of healthcare access during the pandemic, particularly in low- and middle-income countries.

Studies indicate greenhouse gas emissions following permafrost thaw will amplify current rates of atmospheric warming, a process referred to as the permafrost carbon feedback. However, large uncertainties exist regarding the timing and magnitude of the permafrost carbon feedback, in part due to uncertainties associated with subsurface permafrost parameterization and structure. Development of robust parameter estimation methods for permafrost-rich soils is becoming urgent under accelerated warming of the Arctic. Improved parameterization of the subsurface properties in land system models would lead to improved predictions and a reduction of modeling uncertainty. In this work we set the groundwork for future parameter estimation (PE) studies by developing and evaluating a joint PE algorithm that estimates soil porosities and thermal conductivities from time series of soil temperature and moisture measurements and discrete in-time electrical resistivity measurements. The algorithm utilizes the Model-Independent Parameter Estimation and Uncertainty Analysis toolbox and coupled hydrological-thermal-geophysical modeling. We test the PE algorithm against synthetic data, providing a proof of concept for the approach. We use specified subsurface porosities and thermal conductivities and coupled models to set up a synthetic state, perturb the parameters, and then verify that our PE method is able to recover the parameters and synthetic state. To evaluate the accuracy and robustness of the approach we perform multiple tests for a perturbed set of initial starting parameter combinations. In addition, we varied types and quantities of data to better understand the optimal dataset needed to improve the PE method. The results of the PE tests suggest that using multiple types of data improve the overall robustness of the method. Our numerical experiments indicate that special care needs to be taken during the field experiment setup so that (1) the vertical distance between adjacent measurement sensors allows the signal variability in space to be resolved and (2) the longer time interval between resistivity snapshots allows signal variability in time to be resolved.

Estimating the incidence of infections caused by SARS-CoV-2 that are frequently asymptomatic is challenging when using routine passive surveillance methods. Antibodies can provide a record of previous infection, whether symptomatic [...]

Introduction: The extensive disruptions of the COVID-19 pandemic have led to heightened concerns about mental health sequelae. There has been significant interest in identifying factors associated with psychosocial vulnerability or resilience. Aims: This study examined associations of trait gratitude with mental health difficulties among community residents in a southern state of the US. Methods: In this cross-sectional online investigation, 543 adults were assessed during an earlier phase of the pandemic, characterized by the reopening of facilities but mounting infection rates. Participants were evaluated using a validated measure of trait gratitude and clinically relevant screening assess-ments of depression, anxiety, and trauma symptoms. Results: After adjusting for a range of pandemic-associated burdens and sociodemographic factors, multivariable analyses indicated that gratitude was significantly related to diminished levels of depres-sion, anxiety, and trauma. These effects remained significant after additional adjustment for other psychosocial resources (religiousness and perceived support). Conclusions: Findings provide novel information regarding relationships between gratitude and reduced mental health difficulties among community residents during a stressful period early in the pandemic. Results set the stage for longitudinal research. A disposition to identify and appreciate beneficial experiences might contribute to more favorable adaptation to communal crises, and warrants further investigation.

An international team of researchers finds high potential for improving climate projections by a more comprehensive treatment of largely ignored Arctic vegetation types, underscoring the importance of Arctic energy exchange measuring stations.

Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.

Objective: To summarize the prevalence of Long COVID symptoms among the general population reported in published articles from the pre-omicron SARS-CoV2 era. This narrative review examined 21 symptoms. Methods: A PubMed/manual search returned 114 articles on general Long COVID symptoms. Manuscripts were excluded if they were not research studies, did not report symptom prevalence, or used a pediatric population. Ninety-eight studies were selected for review and fifty-nine met the criteria for inclusion. The risk of bias was assessed with the Hoy critical appraisal tool. Results: After excluding studies with a high risk of bias, meta-analysis of prevalence for 21 symptom categories ranged from 2.6–28.7% in studies based on surveys to 0.3–7.1% in studies based on electronic health record data. Conclusions: Long COVID symptom studies are limited by the variability in study design and representation of the general population. Further research is needed to effectively cluster symptoms in meaningful ways that enable focused treatment. [ABSTRACT FROM AUTHOR]

Research Question: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? Background: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on the hospital length of stay, duration of mechanical ventilation, and intensive-care-unit length of stay in critically ill patients with severe coronavirus-19 pneumonia. Methods: Records of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive-care-unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. Results: Fifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or of other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients, and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs. 2.5%, risk difference [RD] = 28.8%, p < 0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose–response relationship between the risk of fungal infection and number of tocilizumab doses received, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD = 17.5%), and 50% with two doses (RD = 47.5%) (trend test p < 0.001). In addition, ICU LOS (23.4 days vs. 9.0 days, p < 0.01), the duration of mechanical ventilation (18.9 vs. 3.5 days, p = 0.01), and hospital length of stay (LOS) (29.1 vs. 15.5, p < 0.01) were increased in patients that received tocilizumab. Conclusions: Repurposed immunomodulator therapies, such as tocilizumab, are now recommended treatments for severe coronavirus-2019 pneumonia, but safety concerns remain. In this early pandemic cohort, the addition of tocilizumab to dexamethasone was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab use was also associated with increased ICU and hospital LOSs and duration of mechanical ventilation.

The pathways and timing of drainage from the inundated centers of ice-wedge polygons in a warming climate have important implications for carbon flushing, advective heat transport, and transitions from methane to carbon dioxide dominated emissions. Here, we expand on previous research using a recently developed analytical model of drainage from a low-centered polygon. Specifically, we perform (1) a calibration to field data identifying necessary model refinements and (2) a rigorous model sensitivity analysis that expands on previously published indications of polygon drainage characteristics. This research provides intuition on inundated polygon drainage by presenting the first in-depth analysis of drainage within a polygon based on hydrogeological first principles. We verify a recently developed analytical solution of polygon drainage through a calibration to a season of field measurements. Due to the parsimony of the model, providing the potential that it could fail, we identify the minimum necessary refinements that allow the model to match water levels measured in a low-centered polygon. We find that (1) the measured precipitation must be increased by a factor of around 2.2, and (2) the vertical soil hydraulic conductivity must decrease with increasing thaw depth. Model refinement (1) accounts for runoff from rims into the ice-wedge polygon pond during precipitation events and possible rain gauge undercatch, while refinement (2) accounts for the decreasing permeability of deeper soil layers. The calibration to field measurements supports the validity of the model, indicating that it is able to represent ice-wedge polygon drainage dynamics. We then use the analytical solution in non-dimensional form to provide a baseline for the effects of polygon aspect ratios (radius to thaw depth) and coefficient of hydraulic conductivity anisotropy (horizontal to vertical hydraulic conductivity) on drainage pathways and temporal depletion of ponded water from inundated ice-wedge polygon centers. By varying the polygon aspect ratio, we evaluate the relative effect of polygon size (width), inter-annual increases in active-layer thickness, and seasonal increases in thaw depth on drainage. The results of our sensitivity analysis rigorously confirm a previous analysis indicating that most drainage through the active layer occurs along an annular region of the polygon center near the rims. This has important implications for transport of nutrients (such as dissolved organic carbon) and advection of heat towards ice-wedge tops. We also provide a comprehensive investigation of the effect of polygon aspect ratio and anisotropy on drainage timing and patterns, expanding on previously published research. Our results indicate that polygons with large aspect ratios and high anisotropy will have the most distributed drainage, while polygons with large aspect ratios and low anisotropy will have their drainage most focused near their periphery and will drain most slowly. Polygons with small aspect ratios and high anisotropy will drain most quickly. These results, based on parametric investigation of idealized scenarios, provide a baseline for further research considering the geometric and hydraulic complexities of ice-wedge polygons.

Introduction: Trigeminal neuralgia (TGN) is a debilitating pain disorder most commonly due to compression of the trigeminal nerve (CN V) by the superior cerebellar artery (SCA). Less commonly, other arteries or veins may compress CN V, and rarely, vascular malformations may be the culprit. SCA aneurysm are uncommon, especially when arising beyond the SCA-basilar bifurcation. Here we report a case of a distal SCA aneurysm resulting in refractory TGN. Brief Case Description: A 78-year-old female presented with frequent attacks of severe, lancinating right V2 and V3 distribution face pain since 2008. She had responded only transiently to carbamazepine and other neuropathic agents. She underwent stereotactic neurosurgery in 2008 and 2011 with only temporary relief. Subsequent glycerol rhizolyses in 2018 and 2019 did not provide lasting relief. Finally, in January 2021, she underwent microvascular decompression (MVD) during which a small, fusiform (or “blister”) distal SCA aneurysm was found to be compressing CN V directly at the dorsal root entry zone. This lesion was obliterated intraoperatively, and CN V was wrapped. At the time of this publication, she has continued to be pain-free following surgery. Conclusion: TGN is a debilitating pain disorder and is most often caused by the SCA or a pontomesencephalic vein. Distal SCA (SCA-2) aneurysms are extremely uncommon, but large SCA-2 aneurysms have been reported to cause TGN, albeit in only 2 instances. Here, we present the first reported case of refractory TGN due to a small, “blister” SCA-2 aneurysm immediately adjacent to the trigeminal DREZ.

Recently, the use of stereoscopic three-dimensional (3-D) projection displays has increased in geoscience education. One concern in employing 3-D projection systems in large lecture halls, however, is that the 3-D effect is reported to diminish with increased angle and distance from the stereoscopic display. The goal of this work was to study that effect in a classroom ''real-world'' lecture environment where such technology would actually be employed. Introductory physical geography concepts were taught to undergraduate students at the University of Kansas through a GeoWall (passive 3-D projection system) display with either static diagrams or interactive globe imagery (Google Earth). Student learning was gauged using both formative (in-class clicker questions) and summative (exam) assessments. We evaluated the spatial structure of students' formative and summative scores for two concepts: Earth-Sun geometries, taught with static images only, and arid landscapes and aeolian processes, taught with Google Earth only. Three significant results were observed: (1) students' ability to accurately observe the 3-D effect was not restricted to the recommended seating angles when using static images, (2) no spatial patterns of improved learning were observed when using static images only; and (3) a significant difference in learning was observed based on seating angles when using Google Earth. Although this study did not compare learning outcomes against a control group, as would be done in a tightly controlled experimental setting, our findings imply that seating angle should be considered in the design of a new classroom equipped with a stereoscopic display or when choosing an existing classroom to retrofit with this technology, particularly, if interactive, globe imagery, such as Google Earth, is used as a primary teaching tool.

The OPRM1 gene codes for the mu opioid receptor (MOR) and polymorphisms are associated with complex patient clinical responses. The most studied single nucleotide polymorphism (SNP) in OPRM1 is adenine (A) substituted by guanine (G) at position 118 (118A>G, rs1799971) leading to a substitution of asparagine (Asn) for aspartic acid (Asp) at position 40 in the N terminus of the resulting protein. To date, no structural explanation for the associated clinical responses resulting from the 118A>G polymorphism has been proposed. We utilized computational modeling paired with functional cellular assays to predict unstructured N‐ and C‐terminal regions of MOR‐1. Using molecular docking and post‐docking energy minimizations with morphine, we show that the extracellular substitution of Asn at position 40 alters the cytoplasmic C‐terminal conformation, while leaving the G‐protein binding interface unaffected. A real‐time BRET assay measuring G‐protein and β‐arrestin association with MOR r generated data that tested this prediction. Consistent with this in silico prediction, we show changes in morphine‐mediated β‐arrestin association with receptor variants with little change in morphine‐mediated G‐protein association comparing MOR‐1 wild type (WT) to MOR‐1118A>G. We tested the system with different opioid agonists, the OPRM1 118A>G SNP, and different MOR splice variants (MOR‐1 and MOR‐1O). These results are consistent with the observation that patients with the 118A>G OPRM1 allele respond more readily to fentanyl than to morphine. In conclusion, the 118A>G substitution alters receptor responses to opioids through variable C‐terminal domain movements that are agonist and splice variant dependent. [ABSTRACT FROM AUTHOR]

The Devonian-Carboniferous (D-C; 359 Ma) boundary is marked by widespread deposition of organic-matter-rich black shales associated with the Hangenberg mass extinction event. The Exshaw Formation spans the D-C boundary in the Western Canada Sedimentary Basin (WCSB) and includes the basal Exshaw Shale deposited under broadly anoxic waters. The sediments at the base of the Exshaw Shale were deposited synchronously during a transgressive event across the WCSB, spanning the geographic variability of the basin. The variable Corg content of the shale was affected by local nutrient upwelling and paleotectonic features impacting water depth and circulation. To characterize the link between paleogeography and nutrient cycling, geographic (N = 20 locations) and stratigraphic (N = 6 locations) trends of δ13^^ and δ15^^ were examined throughout the WCSB, representing a range of depositional settings. The δ15^^ values range between 0.0 and 6.3%" and δ13^^ from -29.5 to -26.8%. Phytoplankton production in focused upwelling zones acquired a relatively 15N-depleted signature through isotopic fractionation during nutrient assimilation, and the residual nutrient pool was 15N-enriched. The advection of surface waters away from the location of upwelling supported additional phytoplankton growth and the deposition of sediments with higher δ1^ values. The stratigraphic sections include black laminated and burrowed mudrock sequences that record changes in paleoredox conditions, water depth, and tectonism over time. Up-core from the base of the Exshaw, the Corg content decreases and simultaneously δ15^^ increases, suggesting a decrease in eutrophic conditions. Variable δ13^^ and δ15^^ trends demonstrate that there is no "type" isotopic profile spanning the D-C boundary in the WCSB. [ABSTRACT FROM AUTHOR]

More than 40 million Americans (1) lack broadband access, including more (2) than 22 percent in rural areas and 27 percent on tribal lands. During the pandemic, stories abounded about [...]

BackgroundThere are reports of developmental and reproductive health effects associated with the widely used biocide triclosan.ObjectiveApply the Navigation Guide systematic review methodology to answer the question: Does exposure to triclosan have adverse effects on human development or reproduction?MethodsWe applied the first 3 steps of the Navigation Guide methodology: 1) Specify a study question, 2) Select the evidence, and 3) Rate quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using pre-specified criteria. We assessed the number and type of all relevant studies. We evaluated each included study for risk of bias and rated the quality and strength of the evidence for the selected outcomes. We conducted a meta-analysis on a subset of suitable data.ResultsWe found 4282 potentially relevant records, and 81 records met our inclusion criteria. Of the more than 100 endpoints identified by our search, we focused our evaluation on hormone concentration outcomes, which had the largest human and non-human mammalian data set. Three human studies and 8 studies conducted in rats reported thyroxine levels as outcomes. The rat data were amenable to meta-analysis. Because only one of the human thyroxine studies quantified exposure, we did not conduct a meta-analysis of the human data. Through meta-analysis of the data for rats, we estimated for prenatal exposure a 0.09% (95% CI: -0.20, 0.02) reduction in thyroxine concentration per mg triclosan/kg-bw in fetal and young rats compared to control. For postnatal exposure we estimated a 0.31% (95% CI: -0.38, -0.23) reduction in thyroxine per mg triclosan/kg-bw, also compared to control. Overall, we found low to moderate risk of bias across the human studies and moderate to high risk of bias across the non-human studies, and assigned a "moderate/low" quality rating to the body of evidence for human thyroid hormone alterations and a "moderate" quality rating to the body of evidence for non-human thyroid hormone alterations.ConclusionBased on this application of the Navigation Guide systematic review methodology, we concluded that there was "sufficient" non-human evidence and "inadequate" human evidence of an association between triclosan exposure and thyroxine concentrations, and consequently, triclosan is "possibly toxic" to reproductive and developmental health. Thyroid hormone disruption is an upstream indicator of developmental toxicity. Additional endpoints may be identified as being of equal or greater concern as other data are developed or evaluated.

Objective: Glomerular filtration rate (GFR) may influence concentrations of biomarkers of exposure and their etiologic significance in observational studies of associations between environmental contaminants and fetal growth. It is unknown whether the size of a developing fetus affects maternal GFR such that a small fetus leads to reduced plasma volume expansion (PVE), reduced GFR and subsequent higher concentrations of biomarkers in maternal serum. Our objective was to answer the question: "Is there an association between fetal growth and maternal GFR in humans?"Methods: We adapted and applied the Navigation Guide systematic review methodology to assess the evidence of an association between fetal growth and GFR, either directly or indirectly via reduction in PVE.Results: We identified 35 relevant studies. We rated 31 human and two non-human observational studies as "low" quality and two experimental non-human studies as "very low" quality. We rated all three evidence streams as "inadequate". The association between fetal growth and GFR was "not classifiable" according to pre-specified definitions.Conclusions: There is currently insufficient evidence to support the plausibility of a reverse causality hypothesis for associations between exposure to environmental chemicals during pregnancy and fetal growth. Further research would be needed to confirm or disprove this hypothesis.

Enrollment in online courses has outpaced overall university enrollment for the past several years. The growth of online courses does not appear to be slowing. The purpose of this study was to compare course completion and student academic performance between online and traditional courses. Archival data from the host university student records system was collected using the Structured Query Language. Descriptive statistics were used to analyze student characteristics. Chi-square analysis was used to determine if statistically significant differences existed between students enrolled in online and traditional courses when comparing course completion and academic performance. Analysis found statistically significant differences existed in both course completion and academic performance for students enrolled in online versus traditional courses. Additional analysis indicated statistically significant differences existed in course completion by course discipline.

Abstract Intraventricular melanoma is a very rare and highly malignant disease. Safe resection is the mainstay of treatment, but no standard guidelines exist for adjuvant therapy. Early histologic and molecular diagnosis is key for improved survival.