ABSTRACT
BACKGROUND: Online video hosting websites such as YouTube have been increasingly used by medical institutions to spread information about new and exciting topics. However, due to the large number of videos uploaded daily and the lack of peer review, few attempts have been made to assess the quantity and quality of information that is uploaded on YouTube. For this study, our team assessed the available content on the transoral robotic surgery (TORS) procedure. METHODS: A qualitative case study model was employed. Videos related to TORS were collected using a unified search protocol. Each video was then analyzed, and metrics of the following data points were collected: views, likes, comments, upload date, length of video, author type, author, and region of origin. Each dataset was analyzed by two distinct authors, and interrater reliability was calculated. Quantitative and qualitative statistics were curated. RESULTS: A total of 124 videos were analyzed for this review. The breakdown of videos was as follows: 15.32% (19) in the educational for patients category, 16.94% (21) in the educational for trainees category, 30.65% (38) in the procedural overview category, 8.87% (11) in the patient experience (PE) category, 10.48% (13) in the promotional category, 12.10% (15) in the other category, and 5.65% (7) in the irrelevant (IR) category. The total number of views across all videos analyzed was 2,589,561. The total number of likes was 14,827, and the total number of comments was 2,606. The average video length was 8.63 minutes. The most viewed category was the PE category at 1,014,738 and the most liked at 1,714. The least viewed category was IR at 21,082. The PE category had the most engagement based on combined comments and likes. The most watched video, with 774,916 views, was in the PE category under the "TORS for Thyroidectomy" search term and was titled "Thyroid Surgery (Thyroidectomy)." CONCLUSION: As the prevalence of online videos regarding medical devices, procedures, and treatments increases, patients and trainees alike will look toward resources such as YouTube to augment their understanding. Patients, providers, and medical education platforms should take heed of the promise and pitfalls of medical content on YouTube.
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BACKGROUND: Down syndrome (DS) is one of the most common chromosomal abnormalities, and children with DS have increased risks of receiving diagnoses of specific comorbidities. AIMS: This study aimed to assess the frequencies and relationships between sleep problems, gastrointestinal (GI) symptoms, comorbid psychopathology, and challenging behavior. METHODS AND PROCEDURES: The Children's Sleep Habits Questionnaire, Gastrointestinal Symptom Inventory, Autism Spectrum Disorder-Comorbid for Children, and Behavior Problems Inventory-Short Form were completed by 123 parents of children and adolescents with DS. OUTCOMES AND RESULTS: The frequency of GI symptoms was 74.8 %, with high frequencies also found for: sleep problems (100 %), challenging behavior (100 %), and moderate to severe levels of comorbid psychopathology (tantrum=80 %; repetitive behavior=63 %; avoidant behavior=82 %; worry/depressed=61 %; conduct behavior=100 %; over-eating=100 %; under-eating=100 %). A significant moderate correlation was found between total GI symptoms and self-injurious behavior frequency. Children who presented with abdominal pain engaged in self-injurious behavior more frequently than those with no abdominal pain. CONCLUSIONS AND IMPLICATIONS: Findings indicated a high frequency of sleep problems, comorbid psychopathology, GI symptoms, and challenging behavior and demonstrated a relationship between GI symptoms and self-injurious behavior in children and adolescents with DS. This research illustrated the importance of investigating comorbid conditions in individuals with DS. WHAT THIS PAPER ADDS?: Down Syndrome (DS) is a genetic condition characterized by trisomy 21 and is a leading cause of intellectual disability worldwide. The prevalence of DS is commonly associated with advanced maternal age and is associated with multiple comorbid conditions. The current study aimed to investigate the frequency of and relationship between sleep problems, gastrointestinal symptoms, comorbid psychopathology, and challenging behavior in children and adolescents with DS. High-frequency levels were found for sleep problems (100 %), challenging behavior (100 %), gastrointestinal symptoms (74.8 %), and moderate to severe levels of the different comorbid psychopathologies (tantrum=80 %; repetitive behavior=63 %; avoidant behavior=82 %; worry/depressed=61 %; conduct behavior=100 %; over-eating=100 %; under-eating=100 %). Results indicated a significant difference in self-injurious behavior frequency between individuals who presented with abdominal pain and those who did not. This study is the first to investigate the relationship of multiple comorbid conditions in a sample of children with DS. This paper adds to the literature by demonstrating the frequency of a number of comorbid conditions in children and adolescents with DS. The paper also adds novel findings to the literature by investigating the relationships between comorbid conditions in this population. The findings of this paper highlighted the frequency and comorbidities that exist between gastrointestinal symptoms, sleep problems, comorbid psychopathology, and challenging behavior. Analyses indicated that those who presented with abdominal pain, engaged in self-injurious behavior more frequently. Sleep problems, gastrointestinal symptoms, comorbid psychopathology, and challenging behavior in children and adolescents with Down Syndrome.
Subject(s)
Abdominal Pain , Comorbidity , Down Syndrome , Gastrointestinal Diseases , Problem Behavior , Sleep Wake Disorders , Humans , Down Syndrome/epidemiology , Down Syndrome/psychology , Down Syndrome/complications , Child , Female , Male , Adolescent , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/psychology , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/psychology , Problem Behavior/psychology , Abdominal Pain/epidemiology , Abdominal Pain/psychology , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/psychology , Self-Injurious Behavior/epidemiology , Self-Injurious Behavior/psychology , Surveys and QuestionnairesABSTRACT
Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that is associated with an increased risk of developing cutaneous malignancies. Clinical outcomes for these malignancies, including melanoma and keratinocyte cancers (KC), are worse for patients with CLL. Individuals with CLL develop an immunodeficiency of both the adaptive and innate immune system, which plays a role in the increased prevalence of skin cancers. This review focuses on the complex interplay between genetics, immunity, and pathogens that influence the cellular composition and biology of skin tumors and their microenvironment in CLL patients, and in comparison with other chronic hematological malignancies. It is paramount for dermatologists to be aware of the association between CLL (and chronic hematological malignancies more broadly) and cutaneous malignancies. This is a high-risk population who require regular and vigorous dermatologic follow-up.
Subject(s)
Hematologic Neoplasms , Leukemia, Lymphocytic, Chronic, B-Cell , Melanoma , Skin Neoplasms , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Skin Neoplasms/epidemiology , Skin Neoplasms/etiology , Skin Neoplasms/pathology , Melanoma/epidemiology , Risk Factors , Tumor MicroenvironmentABSTRACT
OBJECTIVE: The Corona Radiata (CR) is a large white matter tract in the brain comprising of the anterior CR (aCR), superior CR (sCR), and posterior CR (pCR), which have associations with cognition, self-regulation, and, in schizophrenia, positive symptom severity. This study tested the hypothesis that the microstructural organisation of the aCR, as measured by Fractional Anisotropy (FA) using Diffusion Tensor Imaging (DTI), would relate to poorer social cognitive outcomes and higher positive symptom severity for people with schizophrenia, when compared to healthy participants. We further hypothesised that increased positive symptoms would relate to poorer social cognitive outcomes. METHODS: Data were derived from n = 178 healthy participants (41 % females; 36.11 ± 12.36 years) and 58 people with schizophrenia (30 % females; 42.4 ± 11.1 years). The Positive and Negative Symptom Severity Scale measured clinical symptom severity. Social Cognition was measured using the Reading the Mind in the Eyes Test (RMET) Total Score, as well as the Positive, Neutral, and Negative stimuli valence. The ENIGMA-DTI protocol tract-based spatial statistics (TBSS) was used. RESULTS: There was a significant difference in FA for the CR, in individuals with schizophrenia compared to healthy participants. On stratification, both the aCR and pCR were significantly different between groups, with patients showing reduced white matter tract microstructural organisation. Significant negative correlations were observed between positive symptomatology and reduced microstructural organisation of the aCR. Performance for RMET negative valence items was significantly correlated bilaterally with the aCR, but not the sCR or pCR, and no relationship to positive symptoms was observed. CONCLUSIONS: These data highlight specific and significant microstructural white-matter differences for people with schizophrenia, which relates to positive clinical symptomology and poorer performance on social cognition stimuli. While reduced FA is associated with higher positive symptomatology in schizophrenia, this study shows the specific associated with anterior frontal white matter tracts and reduced social cognitive performance. The aCR may have a specific role to play in frontal-disconnection syndromes, psychosis, and social cognitive profile within schizophrenia, though further research requires more sensitive, specific, and detailed consideration of social cognition outcomes.
Subject(s)
Schizophrenia , White Matter , Female , Humans , Male , White Matter/diagnostic imaging , Diffusion Tensor Imaging/methods , Schizophrenia/complications , Schizophrenia/diagnostic imaging , Social Cognition , Brain , AnisotropyABSTRACT
The immune system plays a key role in the suppression and progression of basal cell carcinoma (BCC). The primary aetiological factor for BCC development is exposure to ultraviolet radiation (UVR) which, particularly in lighter Fitzpatrick skin types, leads to the accumulation of DNA damage. UVR has roles in the generation of an immunosuppressive environment, facilitating cancer progression. Rates of BCC are elevated in immunosuppressed patients, and BCC may undergo spontaneous immune-mediated regression. Histologic and immunohistochemical profiling of BCCs consistently demonstrates the presence of an immune infiltrate and associated immune proteins. Early studies of immune checkpoint inhibitors reveal promising results in BCC. Therefore, the host immune system and tumor responses to it are important in BCC pathogenesis. Understanding these interactions will be beneficial for disease prognostication and therapeutic decisions.
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Cutaneous squamous cell carcinoma (cSCC) is the most common malignancy in immune-suppressed organ transplant recipients (OTRs). Whilst rates of other malignancies (both cutaneous and non-cutaneous) are elevated in this population, the increase is far less striking. This suggests that cSCC must be a highly immunogenic tumor. The tumor immune microenvironment is altered in cSCC from OTRs. It has reduced anti-tumor properties and instead provides an environment that facilitates tumor growth and survival. Understanding the composition and function of the tumor immune microenvironment in cSCC from OTRs is useful for prognostication and therapeutic decisions.
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Conservation decisions are often made in the face of uncertainty because the urgency to act can preclude delaying management while uncertainty is resolved. In this context, adaptive management is attractive, allowing simultaneous management and learning. An adaptive program design requires the identification of critical uncertainties that impede the choice of management action. Quantitative evaluation of critical uncertainty, using the expected value of information, may require more resources than are available in the early stages of conservation planning. Here, we demonstrate the use of a qualitative index to the value of information (QVoI) to prioritize which sources of uncertainty to reduce regarding the use of prescribed fire to benefit Eastern Black Rails (Laterallus jamaicensis jamaicensis), Yellow Rails (Coterminous noveboracensis), and Mottled Ducks (Anas fulvigula; hereafter, focal species) in high marshes of the U.S. Gulf of Mexico. Prescribed fire has been used as a management tool in Gulf of Mexico high marshes throughout the last 30+ years; however, effects of periodic burning on the focal species and the optimal conditions for burning marshes to improve habitat remain unknown. We followed a structured decision-making framework to develop conceptual models, which we then used to identify sources of uncertainty and articulate alternative hypotheses about prescribed fire in high marshes. We used QVoI to evaluate the sources of uncertainty based on their Magnitude, Relevance for decision-making, and Reducibility. We found that hypotheses related to the optimal fire return interval and season were the highest priorities for study, whereas hypotheses related to predation rates and interactions among management techniques were lowest. These results suggest that learning about the optimal fire frequency and season to benefit the focal species might produce the greatest management benefit. In this case study, we demonstrate that QVoI can help managers decide where to apply limited resources to learn which specific actions will result in a higher likelihood of achieving the desired management objectives. Further, we summarize the strengths and limitations of QVoI and outline recommendations for its future use for prioritizing research to reduce uncertainty about system dynamics and the effects of management actions.
Subject(s)
Birds , Ecosystem , Animals , Uncertainty , Ducks , Wetlands , Conservation of Natural Resources/methodsABSTRACT
Polysulfur species have been proposed to be the unknown near-UV absorber in the atmosphere of Venus. Recent work argues that photolysis of one of the (SO)2 isomers, cis-OSSO, directly yields S2 with a branching ratio of about 10%. If correct, this pathway dominates polysulfur formation by several orders of magnitude, and by addition reactions yields significant quantities of S3, S4, and S8. We report here the results of high-level ab-initio quantum-chemistry computations that demonstrate that S2 is not a product in cis-OSSO photolysis. Instead, we establish a novel mechanism in which S2 is formed in a two-step process. Firstly, the intermediate S2O is produced by the coupling between the S and Cl atmospheric chemistries (in particular, SO reaction with ClS) and in a lesser extension by O-abstraction reactions from cis-OSSO. Secondly, S2O reacts with SO. This modified chemistry yields S2 and subsequent polysulfur abundances comparable to the photolytic cis-OSSO mechanism through a more plausible pathway. Ab initio quantification of the photodissociations at play fills a critical data void in current atmospheric models of Venus.
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Clinical and laboratory studies have shown that environmental exposure to cadmium produces damage to several organs, including bones, lungs, and kidneys. The involvement of cadmium in central nervous system (CNS) disorders has also been widely reported, but the precise pathophysiological mechanism is not yet fully understood. Children who were exposed to cadmium during pregnancy are known to suffer from developmental delays, learning difficulties, attention deficit hyperactivity disorder (ADHD), and other cognitive and neurobehavioral deficits. Results from numerous studies suggest that dysfunction of the blood-brain barrier (BBB) structures is an important step in the neurotoxicity of cadmium. A rat-specific BBB marker protein, the endothelial barrier antigen (EBA), has been previously isolated and classified by Sternberger and others. The mouse IgG1 clone, anti-endothelial barrier antigen (anti-EBA), detects a protein triplet (23.5kDa, 25 kDa, and 30kDa) localized to the luminal surface of central and peripheral nervous system (CNS and PNS) vascular endothelial cells with selective permeability barrier functions. This marker has been widely used for characterizing BBB alterations under demyelinating, inflammatory, and other CNS pathologies. Many studies have been published using the rat model system for studying the neurotoxic effect of acute and chronic exposure to cadmium. We applied the indirect immunofluorescent techniques using the anti-EBA antibody in conjunction with the Olympus cellSens computerized image analysis to detect and quantify the surface areas of BBB-competent microvessel profiles in paraformaldehyde-fixed, paraffin-embedded brains of term-delivered young rats after intraperitoneal injection of a single dose of cadmium chloride. We detected a statistically significant reduction in EBA-positive microvessel surface areas in the forebrain (t = 5.86, df = 1789, p-value < 0.001) and cerebellum (t=73.40, df=1337, p < 0.001) of cadmium-treated rats compared to the normal controls. Thus, this study supports the hypothesis that the EBA is a sensitive and measurable indicator for quantitative assessment of the impact of cadmium exposure in the developing rat brain.
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Persons experiencing homelessness (PEH) are at heightened risk for infection, morbidity, and mortality from COVID-19. However, health consequences of the pandemic extend far beyond those directly caused by the virus. This scoping review aimed to explore the impacts of the COVID-19 pandemic on the health and well-being of PEH in North America and Europe. A systematic search of academic and grey literature was conducted in September 2021. To be included, studies had to include primary data related to the impact of the pandemic on health or well-being of PEH and be written in English. All potentially relevant references were independently screened by two reviewers, and minor conflicts were settled with input of a third reviewer. A total of 96 articles met criteria for inclusion. Data extraction was completed for all included studies, and findings synthesised and presented thematically. Numerous health impacts of the pandemic on PEH were identified, including SARS-CoV-2 infection, morbidity, mortality, and hospitalisation, fear of infection, access to housing, hygiene, PPE, food, as well as mental health, substance use, other health-related outcomes and treatment services. Gaps in the literature relating to persons using alcohol, access to mental health support, and violence were also identified. Implications for future research are discussed.
Subject(s)
COVID-19 , Ill-Housed Persons , COVID-19/epidemiology , Ill-Housed Persons/psychology , Humans , North America/epidemiology , Pandemics , SARS-CoV-2ABSTRACT
Resource allocation for land acquisition is a common multiobjective problem that involves complex trade-offs. The National Wildlife Refuge System (NWRS) of the U.S. Fish and Wildlife Service currently uses the Targeted Resource Acquisition Comparison Tool (TRACT) to allocate funds from the Migratory Bird Conservation Fund (MBCF; established through the Migratory Bird Hunting and Conservation Act of 1934) for land acquisition based on cost-benefit analysis, regional priority rankings of candidate land parcels available for acquisition, and the overall biological contribution to duck population objectives. However, current policy encourages decision makers to consider societal and economic benefits of lands acquired, in addition to their biological benefits to waterfowl. These decisions about portfolio elements (i.e., individual land parcels) require an analysis of the difficult trade-offs among multiple objectives. In the last decade the application of multicriteria decision analysis (MCDA) methods has been instrumental in aiding decision makers with complex multiobjective decisions. In this study, we present an alternative approach to developing land-acquisition portfolios using MCDA and modern portfolio theory (MPT). We describe the development of a portfolio decision analysis tool using constrained optimization for land-acquisition decisions by the NWRS. We outline the decision framework, describe development of the prototype tool in Microsoft Excel, and test the results of the tool using land parcels submitted as candidates for MBCF funding in 2019. Our results indicate that the constrained optimization outperformed the traditional TRACT method and ad hoc portfolios developed using current NWRS criteria.
Subject(s)
Animals, Wild , Birds , Conservation of Natural Resources , Animals , Cost-Benefit AnalysisABSTRACT
The downregulation of sclerostin in osteocytes mediates bone formation in response to mechanical cues and parathyroid hormone (PTH). To date, the regulation of sclerostin has been attributed exclusively to the transcriptional downregulation of the Sost gene hours after stimulation. Using mouse models and rodent cell lines, we describe the rapid, minute-scale post-translational degradation of sclerostin protein by the lysosome following mechanical load and PTH. We present a model, integrating both new and established mechanically and hormonally activated effectors into the regulated degradation of sclerostin by lysosomes. Using a mouse forelimb mechanical loading model, we find transient inhibition of lysosomal degradation or the upstream mechano-signaling pathway controlling sclerostin abundance impairs subsequent load-induced bone formation by preventing sclerostin degradation. We also link dysfunctional lysosomes to aberrant sclerostin regulation using human Gaucher disease iPSCs. These results reveal how bone anabolic cues post-translationally regulate sclerostin abundance in osteocytes to regulate bone formation.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Bone Morphogenetic Proteins/metabolism , Lysosomes/metabolism , Osteocytes/metabolism , Osteogenesis/drug effects , Animals , Bone and Bones/metabolism , Cell Line , Cues , Down-Regulation/drug effects , Female , Gaucher Disease/metabolism , Genetic Markers , Humans , Male , Mice , Mice, Inbred C57BL , Parathyroid Hormone/metabolism , Parathyroid Hormone/pharmacology , Rats , Signal Transduction/drug effectsABSTRACT
Western Snowy Plovers (Charadrius nivosus nivosus) are federally listed under the US Endangered Species Act as Threatened. They occur along the US Pacific coastline and are threatened by habitat loss and destruction and excessive levels of predation and human disturbance. Populations have been monitored since the 1970s for distribution, reproduction, and survival. Since the species was federally listed in 1993 and a recovery plan was approved under the US Fish and Wildlife Service in 2007, recovery actions have resulted in growing populations with increased presence at breeding and wintering sites throughout their Pacific Coast range. This success has created logistical challenges related to monitoring a recovering species and a need for identifying and instituting the best monitoring approach given recovery goals, budgets, and the likelihood of monitoring success. We devised and implemented a structured decision analysis to evaluate nine alternative monitoring strategies. The analysis included inviting plover biologists involved in monitoring to score each strategy according to a suite of performance measures. Using multi-attribute utility theory, we combined scores across the performance measures for each monitoring strategy, and applied weighted utility values to show the implications of tradeoffs and find optimal decisions. We evaluated four scenarios for weighting the monitoring objectives and how risk attitude affects optimal decisions. This resulted in identifying six strategies that best meet recovery needs and were Pareto optimal for cost-effective monitoring. Results were presented to the US Fish and Wildlife Service, responsible for monitoring as well as for consideration to ensure consistent monitoring methods across the species' range. Our use of structured decision-making can be applied to cases of other species once imperiled but now on the road to recovery.
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Management of a complex trauma patient is a critical skill for medical students, particularly during a general surgery or emergency medicine clerkship. However, gaining proficiency with this skillset may be challenging without prior medical or simulation experience. The aim of this technical report is to present a comprehensive high-fidelity medical simulation of a polytraumatized patient with numerous injuries sustained from a 20-foot fall. As the scenario unfolds, students identify multisystem injuries including acute hemorrhage, femur fracture, tension pneumothorax, and traumatic brain injury. The case was designed as an assessment tool to evaluate the knowledge of preclinical medical students obtained through a one-day workshop on the primary survey. This technical report provides simulation designers with a premade script, flowchart, labs, images, and supplies needed to successfully recreate the case.
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Modern technology has perfected the synthesis of catalysts such as zeolites and mesoporous silicas using organic structure directing agents (SDA) and their industrial use to catalyze a large variety of organic reactions within their pores. We suggest that early in prebiotic evolution, synergistic interplay arose between organic species in aqueous solution and silica formed from rocks by dynamic dissolution-recrystallization. The natural organics, for example, amino acids, small peptides, and fatty acids, acted as SDA for assembly of functional porous silica structures that induced further polymerization of amino acids and peptides, as well as other organic reactions. Positive feedback between synthesis and catalysis in the silica-organic system may have accelerated the early stages of abiotic evolution by increasing the formation of polymerized species.
Subject(s)
Amino Acids/chemistry , Peptides/chemistry , Silicon Dioxide/chemistry , Catalysis , Earth, Planet , Evolution, Chemical , Origin of Life , Polymerization , Zeolites/chemistryABSTRACT
Several years ago, our research group forwarded a model of goal-directed reaching and aiming that describes the processes involved in the optimization of speed, accuracy, and energy expenditure Elliott et al. (Psychol Bull 136:1023-1044, 2010). One of the main features of the model is the distinction between early impulse control, which is based on a comparison of expected to perceived sensory consequences, and late limb-target control that involves a spatial comparison of limb and target position. Our model also emphasizes the importance of strategic behaviors that limit the opportunity for worst-case or inefficient outcomes. In the 2010 paper, we included a section on how our model can be used to understand atypical aiming/reaching movements in a number of special populations. In light of a recent empirical and theoretical update of our model Elliott et al. (Neurosci Biobehav Rev 72:95-110, 2017), here we consider contemporary motor control work involving typical aging, Down syndrome, autism spectrum disorder, and tetraplegia with tendon-transfer surgery. We outline how atypical limb control can be viewed within the context of the multiple-process model of goal-directed reaching and aiming, and discuss the underlying perceptual-motor impairment that results in the adaptive solution developed by the specific group.
Subject(s)
Autism Spectrum Disorder , Goals , Extremities , Humans , Movement , Problem Solving , Psychomotor PerformanceABSTRACT
The Sun is 16O-enriched (Δ17O = -28.4 ± 3.6) relative to the terrestrial planets, asteroids, and chondrules (-7 < Δ17O < 3). Ca,Al-rich inclusions (CAIs), the oldest Solar System solids, approach the Sun's Δ17O. Ultraviolet CO self-shielding resulting in formation of 16O-rich CO and 17,18O-enriched water is the currently favored mechanism invoked to explain the observed range of Δ17O. However, the location of CO self-shielding (molecular cloud or protoplanetary disk) remains unknown. Here we show that CAIs with predominantly low (26Al/27Al)0, <5 × 10-6, exhibit a large inter-CAI range of Δ17O, from -40 to -5. In contrast, CAIs with the canonical (26Al/27Al)0 of ~5 × 10-5 from unmetamorphosed carbonaceous chondrites have a limited range of Δ17O, -24 ± 2. Because CAIs with low (26Al/27Al)0 are thought to have predated the canonical CAIs and formed within first 10,000-20,000 years of the Solar System evolution, these observations suggest oxygen isotopic heterogeneity in the early solar system was inherited from the protosolar molecular cloud.
ABSTRACT
Skeletal remodeling is driven in part by the osteocyte's ability to respond to its mechanical environment by regulating the abundance of sclerostin, a negative regulator of bone mass. We have recently shown that the osteocyte responds to fluid shear stress via the microtubule network-dependent activation of NADPH oxidase 2 (NOX2)-generated reactive oxygen species and subsequent opening of TRPV4 cation channels, leading to calcium influx, activation of CaMKII, and rapid sclerostin protein downregulation. In addition to the initial calcium influx, purinergic receptor signaling and calcium oscillations occur in response to mechanical load and prior to rapid sclerostin protein loss. However, the independent contributions of TRPV4-mediated calcium influx and purinergic calcium oscillations to the rapid sclerostin protein downregulation remain unclear. Here, we showed that NOX2 and TRPV4-dependent calcium influx is required for calcium oscillations, and that TRPV4 activation is both necessary and sufficient for sclerostin degradation. In contrast, calcium oscillations are neither necessary nor sufficient to acutely decrease sclerostin protein abundance. However, blocking oscillations with apyrase prevented fluid shear stress induced changes in osterix (Sp7), osteoprotegerin (Tnfrsf11b), and sclerostin (Sost) gene expression. In total, these data provide key mechanistic insights into the way bone cells translate mechanical cues to target a key effector of bone formation, sclerostin.
Subject(s)
Calcium Signaling , TRPV Cation Channels , Calcium/metabolism , Osteocytes/metabolism , Stress, Mechanical , TRPV Cation Channels/metabolismABSTRACT
In response to global habitat loss, many governmental and non-governmental organizations have implemented land acquisition programs to protect critical habitats permanently for priority species. The ability of these protected areas to meet future management objectives may be compromised if the effects of climate change are not considered in acquisition decisions. Unfortunately, the effects of climate change on ecological systems are complex and plagued by uncertainty, making it difficult for organizations to prioritize research needs to improve decision-making. Herein, we demonstrate the use of qualitative value of information analysis to identify and prioritize which sources of uncertainty should be reduced to improve land acquisition decisions to protect migratory birds in the face of climate change. The qualitative value of information analysis process involves four steps: (i) articulating alternative hypotheses; (ii) determining the magnitude of uncertainty regarding each hypothesis; (iii) evaluating the relevance of each hypothesis to acquisition decision-making; and (iv) assessing the feasibility of reducing the uncertainty surrounding each hypothesis through research and monitoring. We demonstrate this approach using the objectives of 3 U.S. federal land acquisition programs that focus on migratory bird management. We used a comprehensive literature review, expert elicitation, and professional judgement to evaluate 11 hypotheses about the effect of climate change on migratory birds. Based on our results, we provide a list of priorities for future research and monitoring to reduce uncertainty and improve land acquisition decisions for the programs considered in our case study. Reducing uncertainty about how climate change will influence the spatial distribution of priority species and biotic homogenization were identified as the highest priorities for future research due to both the value of this information for improving land acquisition decisions and the feasibility of reducing uncertainty through research and monitoring. Research on how changes in precipitation patterns and winter severity will influence migratory bird abundance is also expected to benefit land acquisition decisions. By contrast, hypotheses about phenology and migration distance were identified as low priorities for research. By providing a rigorous and transparent approach to prioritizing research, we demonstrate that qualitative value of information is a valuable tool for prioritizing research and improving management decisions in other complex, high-uncertainty cases where traditional quantitative value of information analysis is not possible. Given the inherent complexity of ecological systems under climate change, and the difficulty of identifying management-relevant research priorities, we expect this approach to have wide applications within the field of natural resource management.
Subject(s)
Animal Migration , Birds , Climate Change , Research/trends , Animals , United StatesABSTRACT
Dynamic stability provided by muscles is integral for function and integrity of the glenohumeral joint. Although the high degree of inter-individual variation that exists in musculoskeletal geometry is associated with shoulder injuries, there is limited research associating the effects of muscle geometry on the potential stabilizing capacities of shoulder muscles. The purpose of this investigation was to evaluate the stabilizing functions of the scapulohumeral muscles using computational modeling and to quantify the sensitivity of muscle stabilizing roles to changes in muscle geometry. Muscle stability ratios in the superior/inferior and anterior/posterior directions were computed as the ratio between the muscle's shear components relative to compression throughout arm elevation in the scapular plane. Muscle attachment locations on the clavicle, scapula, and humerus were iteratively adjusted using Monte Carlo simulations. Consistent with previous experimental studies, the rotator cuff muscles were identified as the primary stabilizers of the glenohumeral joint; whereas the deltoids and coracobrachialis have a strong potential for superiorly translating the humerus at low elevation angles. Variations in the stability ratios due to altered muscle geometry were muscle- and angle-specific. In general, the highest variation was observed for the subscapularis and deltoids (at low elevation angles), while the remaining rotator cuff muscles largely maintained their capacity to provide compressive stabilizing forces at the glenohumeral joint. Changes in muscle stability ratios may affect dynamic stability of the humerus that could differentially predispose individuals to greater risk for injury.