1,226 research outputs found

    Graph Neural Network-Based Anomaly Detection for River Network Systems

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    Water is the lifeblood of river networks, and its quality plays a crucial role in sustaining both aquatic ecosystems and human societies. Real-time monitoring of water quality is increasingly reliant on in-situ sensor technology. Anomaly detection is crucial for identifying erroneous patterns in sensor data, but can be a challenging task due to the complexity and variability of the data, even under normal conditions. This paper presents a solution to the challenging task of anomaly detection for river network sensor data, which is essential for accurate and continuous monitoring. We use a graph neural network model, the recently proposed Graph Deviation Network (GDN), which employs graph attention-based forecasting to capture the complex spatio-temporal relationships between sensors. We propose an alternate anomaly scoring method, GDN+, based on the learned graph. To evaluate the model's efficacy, we introduce new benchmarking simulation experiments with highly-sophisticated dependency structures and subsequence anomalies of various types. We further examine the strengths and weaknesses of this baseline approach, GDN, in comparison to other benchmarking methods on complex real-world river network data. Findings suggest that GDN+ outperforms the baseline approach in high-dimensional data, while also providing improved interpretability. We also introduce software called gnnad

    Addressing the Legacies of Historical Redlining: Correlations with Measures of Modern Housing Instability

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    "Redlining" of neighborhoods, one of a number of explicitly racist United States federal housing policies in the mid–twentieth century, blocked Black households and other communities of color from accessing home mortgages—and as a result homeownership—for decades. The practice has been linked to present day racialized neighborhood poverty and ongoing negative impacts on formerly redlined neighborhoods.In an attempt to address or mitigate decades of racist housing policies, some policymakers and jurisdictions are considering reparative policies and otherwise prioritizing Black households and others disenfranchised by past racist housing policies. Given the prominence of redlining maps and analyses that find associations between redlining and negative impacts on neighborhoods, some policy makers have focused on redlined areas as a criteria for qualifying for direct assistance.In this brief, we explore the extent to which historical redlining patterns correlate with current risk of housing instability. Using redlining maps for more than 200 cities digitized by the University of Richmond as a base and a number of instability indicators including the Urban Institute's Emergency Rental Assistance Priority (ERA Priority) Index, eviction filing data from the Eviction Lab, and Affirmatively Furthering Fair Housing (AFFH) data, we examine the extent to which redlined areas correlate with concentrations of people who are most at risk of housing instability. It is important to note that the overall practice of restricting access to housing based on race still happens today, but for the purposes of this brief, when we talk about redlining, we mean the legacy of the Federal Housing Administration (FHA)

    CARE Data Principles Data Curation Primer

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    The CARE data principles (Collective benefit, Authority to control, Responsibility, and Ethics) are a conceptual framework meant to ensure ethical collection, sharing, and stewardship of Indigenous data. As part of a workshop hosted by the Data Curation Network in 2022, librarians created a foundational data curation primer on the CARE data principles and how they apply to data management, curation, and sharing. The primer touches on the cultural context regarding the CARE data principles, the historical misuse of Indigenous data, tribal sovereignty, and Indigenous Peoples\u27 right to governance of their data. This session will discuss how CARE principles can be applied and give specific use examples. Librarians can use the primer and CURATE(D) checklist, to consider the ethical use, sharing and preservation of Indigenous data within their institutional repositories

    Mouse Mesenchymal Progenitor Cells Expressing Adipogenic and Osteogenic Transcription Factors Suppress the Macrophage Inflammatory Response

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    Mesenchymal progenitor cell characteristics that can identify progenitor populations with specific functions in immunity are actively being investigated. Progenitors from bone marrow and adipose tissue regulate the macrophage (MΦ) inflammatory response by promoting the switch froman inflammatory to an anti-inflammatory phenotype.Conversely,mesenchymal progenitors fromthe mouse aorta (mAo) support and contribute to the MΦ response under inflammatory conditions.We used cell lines with purported opposing immune-regulatory function, a bonemarrow derivedmesenchymal progenitor cell line (D1) and amouse aorta derived mesenchymal progenitor cell line (mAo). Their interaction and regulation of the MΦ cell response to the inflammatory mediator, lipopolysaccharide (LPS), was examined by coculture. As expected, D1 cells suppressed NO, TNF-, and IL-12p70 production but MΦ phagocytic activity remained unchanged. The mAo cells enhanced NO and TNF- production in coculture and enhanced MΦ phagocytic activity. Using flow cytometry and PCR array, we then sought to identify sets of MSC-associated genes and markers that are expressed by these progenitor populations.We have determined that immune-supportive mesenchymal progenitors highly express chondrogenic and tenogenic transcription factors while immunosuppressive mesenchymal progenitors highly express adipogenic and osteogenic transcription factors. These data will be useful for the isolation, purification, and modification of mesenchymal progenitors to be used in the treatment of inflammatory diseases

    Estimates of Alpha/Beta (alpha/beta) Ratios for Individual Late Rectal Toxicity Endpoints: An Analysis of the CHHiP Trial

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    Purpose: Changes in fraction size of external beam radiation therapy exert nonlinear effects on subsequent toxicity. Commonly described by the linear-quadratic model, fraction size sensitivity of normal tissues is expressed by the α/β ratio. We sought to study individual α/β ratios for different late rectal effects after prostate external beam radiation therapy. Methods and Materials: The CHHiP trial (ISRCTN97182923) randomized men with nonmetastatic prostate cancer 1:1:1 to 74 Gy/37 fractions (Fr), 60 Gy/20 Fr, or 57 Gy/19 Fr. Patients in the study had full dosimetric data and zero baseline toxicity. Toxicity scales were amalgamated to 6 bowel endpoints: bleeding, diarrhea, pain, proctitis, sphincter control, and stricture. Lyman-Kutcher-Burman models with or without equivalent dose in 2 Gy/Fr correction were log-likelihood fitted by endpoint, estimating α/β ratios. The α/β ratio estimate sensitivity was assessed using sequential inclusion of dose modifying factors (DMFs): age, diabetes, hypertension, inflammatory bowel or diverticular disease (IBD/diverticular), and hemorrhoids. 95% confidence intervals (CIs) were bootstrapped. Likelihood ratio testing of 632 estimator log-likelihoods compared the models. Results: Late rectal α/β ratio estimates (without DMF) ranged from bleeding (G1 + α/β = 1.6 Gy; 95% CI, 0.9-2.5 Gy) to sphincter control (G1 + α/β = 3.1 Gy; 95% CI, 1.4-9.1 Gy). Bowel pain modelled poorly (α/β, 3.6 Gy; 95% CI, 0.0-840 Gy). Inclusion of IBD/diverticular disease as a DMF significantly improved fits for stool frequency G2+ (P = .00041) and proctitis G1+ (P = .00046). However, the α/β ratios were similar in these no-DMF versus DMF models for both stool frequency G2+ (α/β 2.7 Gy vs 2.5 Gy) and proctitis G1+ (α/β 2.7 Gy vs 2.6 Gy). Frequency-weighted averaging of endpoint α/β ratios produced: G1 + α/β ratio = 2.4 Gy; G2 + α/β ratio = 2.3 Gy. Conclusions: We estimated α/β ratios for several common late adverse effects of rectal radiation therapy. When comparing dose-fractionation schedules, we suggest using late a rectal α/β ratio ≤ 3 Gy

    Physical activity promotion in chiropractic: a systematic review of clinician-based surveys

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    Background: Physical inactivity is a global health pandemic. Allied healthcare providers, including chiropractors, are well placed to integrate individual physical activity (PA) promotion into routine care. A previous systematic review identified that approximately 90% of chiropractors held a positive opinion towards healthier patient lifestyles; however, the extent to which chiropractors promote PA to their patients within routine care is unclear. This systematic review aimed to describe chiropractors' attitudes towards and current practice in advising, counselling, discussing, supporting, or recommending PA to patients. Methods: Five databases were searched from inception to December 2021 for cross-sectional surveys that explored PA promotion by chiropractors in practice. We assessed the risk of bias of the included studies with the ‘Risk of Bias in Cross-Sectional Surveys of Attitudes and Practices’ tool. Descriptive data were extracted, grouping similar survey questions and responses into emerging categories. Chiropractors’ views regarding the perceived importance and/or their preparedness to counsel and provide PA or exercise information are reported. Results: From 661 studies, 15 met the selection criteria. Surveys included 7999 chiropractors primarily from the USA, UK, Australia, and Sweden. All studies were rated as moderate-to-high risk of bias, with methodological weaknesses characterised by inconsistent reporting of missing data, non-representative samples, low response rates (i.e., less than 60%), and unknown validity of survey instruments. Chiropractors frequently recognised the importance of PA promotion, as demonstrated by the proportion of respondents reporting that they: (1) support the importance of providing PA or exercise information and counselling (64% to 100%); (2) are prepared to provide PA or exercise information and/or counselling to patients (91% to 92%,); (3) frequently obtain PA or exercise information from patients (87% to 97%,); 4) frequently discuss PA or exercise and/or provide PA or exercise information to patients (68% to 99%); and 5) frequently provide PA counselling to patients (50% to 81%.). Conclusion: A large majority of practising chiropractors actively engage with PA promotion. However, the results should be interpreted with caution owing to the moderate-to-high risk of bias of the included studies. Forthcoming research initiatives should explore unbiased surveys, further PA education and training as well as capitalising on chiropractors’ own PA participation

    Chemical traits of cerebral amyloid angiopathy in familial British-, Danish-, and non-Alzheimerʼs dementias

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    Familial British dementia (FBD) and familial Danish dementia (FDD) are autosomal dominant forms of dementia caused by mutations in the integral membrane protein 2B (ITM2B, also known as BRI2) gene. Secretase processing of mutant BRI2 leads to secretion and deposition of BRI2-derived amyloidogenic peptides, ABri and ADan that resemble APP/β-amyloid (Aβ) pathology, which is characteristic of Alzheimer's disease (AD). Amyloid pathology in FBD/FDD manifests itself predominantly in the microvasculature by ABri/ADan containing cerebral amyloid angiopathy (CAA). While ABri and ADan peptide sequences differ only in a few C-terminal amino acids, CAA in FDD is characterized by co-aggregation of ADan with Aβ, while in contrast no Aβ deposition is observed in FBD. The fact that FDD patients display an earlier and more severe disease onset than FBD suggests a potential role of ADan and Aβ co-aggregation that promotes a more rapid disease progression in FDD compared to FBD. It is therefore critical to delineate the chemical signatures of amyloid aggregation in these two vascular dementias. This in turn will increase the knowledge on the pathophysiology of these diseases and the pathogenic role of heterogenous amyloid peptide interactions and deposition, respectively. Herein, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in combination with hyperspectral, confocal microscopy based on luminescent conjugated oligothiophene probes (LCO) to delineate the structural traits and associated amyloid peptide patterns of single CAA in postmortem brain tissue of patients with FBD, FDD as well as sporadic CAA without AD (CAA+) that show pronounced CAA without parenchymal plaques. The results show that CAA in both FBD and FDD consist of N-terminally truncated- and pyroglutamate-modified amyloid peptide species (ADan and ABri), but that ADan peptides in FDD are also extensively C-terminally truncated as compared to ABri in FBD, which contributes to hydrophobicity of ADan species. Further, CAA in FDD showed co-deposition with Aβ x-42 and Aβ x-40 species. CAA+ vessels were structurally more mature than FDD/FBD CAA and contained significant amounts of pyroglutamated Aβ. When compared with FDD, Aβ in CAA+ showed more C-terminal and less N-terminally truncations. In FDD, ADan showed spatial co-localization with Aβ3pE-40 and Aβ3-40 but not with Aβx-42 species. This suggests an increased aggregation propensity of Aβ in FDD that promotes co-aggregation of both Aβ and ADan. Further, CAA maturity appears to be mainly governed by Aβ content based on the significantly higher 500/580 patterns observed in CAA+ than in FDD and FBD, respectively. Together this is the first study of its kind on comprehensive delineation of Bri2 and APP-derived amyloid peptides in single vascular plaques in both FDD/FBD and sporadic CAA that provides new insight in non-AD-related vascular amyloid pathology. (Figure presented.

    Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults

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    Background/aim: Cannabis use is highly prevalent in adolescents; however, little is known about its effects on adolescent brain function. Method: Resting-state functional magnetic resonance imaging was used in matched groups of regular cannabis users (N = 70, 35 adolescents: 16–17 years old, 35 adults: 26–29 years old) and non-regular-using controls (N = 70, 35 adolescents/35 adults). Pre-registered analyses examined the connectivity of seven major cortical and sub-cortical brain networks (default mode network, executive control network (ECN), salience network, hippocampal network and three striatal networks) using seed-based analysis methods with cross-sectional comparisons between user groups and age groups. Results: The regular cannabis use group (across both age groups), relative to controls, showed localised increases in connectivity only in the ECN analysis. All networks showed localised connectivity differences based on age group, with the adolescents generally showing weaker connectivity than adults, consistent with the developmental effects. Mean connectivity across entire network regions of interest (ROIs) was also significantly decreased in the ECN in adolescents. However, there were no significant interactions found between age group and user group in any of the seed-based or ROI analyses. There were also no associations found between cannabis use frequency and any of the derived connectivity measures. Conclusion: Regular cannabis use is associated with changes in connectivity of the ECN, which may reflect allostatic or compensatory changes in response to regular cannabis intoxication. However, these associations were not significantly different in adolescents compared to adults.</p

    Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults

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    BACKGROUND/AIM: Cannabis use is highly prevalent in adolescents; however, little is known about its effects on adolescent brain function. METHOD: Resting-state functional magnetic resonance imaging was used in matched groups of regular cannabis users (N = 70, 35 adolescents: 16-17 years old, 35 adults: 26-29 years old) and non-regular-using controls (N = 70, 35 adolescents/35 adults). Pre-registered analyses examined the connectivity of seven major cortical and sub-cortical brain networks (default mode network, executive control network (ECN), salience network, hippocampal network and three striatal networks) using seed-based analysis methods with cross-sectional comparisons between user groups and age groups. RESULTS: The regular cannabis use group (across both age groups), relative to controls, showed localised increases in connectivity only in the ECN analysis. All networks showed localised connectivity differences based on age group, with the adolescents generally showing weaker connectivity than adults, consistent with the developmental effects. Mean connectivity across entire network regions of interest (ROIs) was also significantly decreased in the ECN in adolescents. However, there were no significant interactions found between age group and user group in any of the seed-based or ROI analyses. There were also no associations found between cannabis use frequency and any of the derived connectivity measures. CONCLUSION: Regular cannabis use is associated with changes in connectivity of the ECN, which may reflect allostatic or compensatory changes in response to regular cannabis intoxication. However, these associations were not significantly different in adolescents compared to adults

    Divergent trajectories of cellular bioenergetics, intermediary metabolism and systemic redox status in survivors and non-survivors of critical illness.

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    BACKGROUND: Numerous pathologies result in multiple-organ failure, which is thought to be a direct consequence of compromised cellular bioenergetic status. Neither the nature of this phenotype nor its relevance to survival are well understood, limiting the efficacy of modern life-support. METHODS: To explore the hypothesis that survival from critical illness relates to changes in cellular bioenergetics, we combined assessment of mitochondrial respiration with metabolomic, lipidomic and redox profiling in skeletal muscle and blood, at multiple timepoints, in 21 critically ill patients and 12 reference patients. RESULTS: We demonstrate an end-organ cellular phenotype in critical illness, characterized by preserved total energetic capacity, greater coupling efficiency and selectively lower capacity for complex I and fatty acid oxidation (FAO)-supported respiration in skeletal muscle, compared to health. In survivors, complex I capacity at 48 h was 27% lower than in non-survivors (p = 0.01), but tended to increase by day 7, with no such recovery observed in non-survivors. By day 7, survivors' FAO enzyme activity was double that of non-survivors (p = 0.048), in whom plasma triacylglycerol accumulated. Increases in both cellular oxidative stress and reductive drive were evident in early critical illness compared to health. Initially, non-survivors demonstrated greater plasma total antioxidant capacity but ultimately higher lipid peroxidation compared to survivors. These alterations were mirrored by greater levels of circulating total free thiol and nitrosated species, consistent with greater reductive stress and vascular inflammation, in non-survivors compared to survivors. In contrast, no clear differences in systemic inflammatory markers were observed between the two groups. CONCLUSION: Critical illness is associated with rapid, specific and coordinated alterations in the cellular respiratory machinery, intermediary metabolism and redox response, with different trajectories in survivors and non-survivors. Unravelling the cellular and molecular foundation of human resilience may enable the development of more effective life-support strategies.MRC, Evelyn Trust, Intensive Care Society, Royal Free Charit
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