Reproducibility comparison among multiangle spectrophotometers

New color-measuring instruments known as multiangle spectrophotometers have been recently created to measure and characterize the goniochromism of special-effect pigments in many materials with a particular visual appearance (metallic, interference, pearlescent, sparkle, or glitter). These devices measure the gonioapparent color from the spectral relative reflectance factor and the L*a*b* values of the sample with different illumination and observation angles. These angles usually coincide with requirements marked in American Society for Testing and Materials (ASTM) and Deutsches Institut Für Normung standards relating to the gonioapparent color, but the results of comparisons between these instruments are still inconclusive. Therefore, the main purpose of this study is to compare several multiangle spectrophotometers at a reproducibility level according to ASTM E2214-08 guidelines. In particular, we compared two X-Rite multi-gonio spectrophotometers (MA98 and MA68II), a Datacolor multi-gonio spectrophotometer (FX10), and a BYK multi-gonio spectrophotometer (BYK-mac). These instruments share only five common measurement geometries: 45° × −30° (as 15°), 45° × −20° (as 25°), 45° × 0° (as 45°), 45° × 30° (as 75°), 45° × 65° (as 110°). Specific statistical studies were used for the reproducibility comparison, including a Hotelling test and a statistical intercomparison test to determine the confidence interval of the partial color differences ΔL*, Δa*, Δb*, and the total color difference ΔE*ab. This was conducted using a database collection of 88 metallic and pearlescent samples that were measured 20 times without the replacement of all the instruments. The final findings show that in most measurement geometries, the reproducibility differences between pairs of instruments are statistically significant, although in general, there is a better reproducibility level at certain common geometries for newer instruments (MA98 and BYK-mac). This means that these differences are due to systematic or bias errors (angle tolerances for each geometry, photometric scales, white standards, etc.), but not exclusively to random errors. However, neither of the statistical tests used is valid to discriminate and quantify the detected bias errors in this comparison between instruments.Spanish Ministry of Science and Innovation; contract grant number: DPI2008-06455-C02-02

The P4->NetFPGA Workflow for Line-Rate Packet Processing

P4 has emerged as the de facto standard language for describing how network packets should be processed, and is becoming widely used by network owners, systems developers, researchers and in the classroom. The goal of the work presented here is to make it easier for engineers, researchers and students to learn how to program using P4, and to build prototypes running on real hardware. Our target is the NetFPGA SUME platform, a 4x10 Gb/s PCIe card designed for use in universities for teaching and research. Until now, NetFPGA users have needed to learn an HDL such as Verilog or VHDL, making it off limits to many software developers and students. Therefore, we developed the P4->NetFPGA workflow, allowing developers to describe how packets are to be processed in the high-level P4 language, then compile their P4 programs to run at line rate on the NetFPGA SUME board. The P4->NetFPGA workflow is built upon the Xilinx P4-SDNet compiler and the NetFPGA SUME open source code base. In this tutorial paper, we provide an overview of the P4 programming language and describe the P4->NetFPGA workflow. We also describe how the workflow is being used by the P4 community to build research prototypes, and to teach how network systems are built by providing students with hands-on experience working with real hardware.Leverhulme Trust Isaac Newton Trust TBD other

Cytokine Profiles in Toxoplasmic and Viral Uveitis

BackgroundUveitis is a major cause of visual impairment throughout the world. Analysis of cytokine profiles in aqueous humor specimens may provide insight into the physiopathological processes that underly retinal damage in this context MethodsUsing a multiplex assay, we determined the concentrations of 17 cytokines and chemokines in aqueous humor specimens obtained from patients with ocular toxoplasmosis or viral uveitis and compared these concentrations with those in specimens obtained from patients with noninfectious intermediate uveitis or cataract ResultsFive mediators (interleukin [IL]-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-4, and IL-10) were detected in >50% of patients in all groups. In contrast, IL-5 and IL-12 were specific for ocular toxoplasmosis, and granulocyte monocyte colony-stimulating factor and IL-1 were specific for viral uveitis; these mediators could present specific markers for diagnostic purposes. Interferon-γ, IL-6, and macrophage inflammatory protein-1β were common markers of ocular toxoplasmosis and viral uveitis. IL-17 was a common marker of ocular toxoplasmosis and intermediate uveitis ConclusionsWe found specific cytokine profiles for each type of uveitis, with large interindividual variations and no etiological or clinical correlations. Ocular cytokine mapping contributes to a better understanding of the physiopathology of specific forms of uveitis and provides guidance for new targeted treatmen

FireDeX: a Prioritized IoT Data Exchange Middleware for Emergency Response

International audienceReal-time event detection and targeted decision making for emerging mission-critical applications, e.g. smart fire fighting, requires systems that extract and process relevant data from connected IoT devices in the environment. In this paper, we propose FireDeX, a cross-layer middleware that facilitates timely and effective exchange of data for coordinating emergency response activities. FireDeX adopts a publish-subscribe data exchange paradigm with brokers at the network edge to manage prioritized delivery of mission-critical data from IoT sources to relevant subscribers. It incorporates parameters at the application, network, and middleware layers into a data exchange service that accurately estimates end-to-end performance metrics (e.g. delays, success rates). We design an extensible queueing theoretic model that abstracts these cross-layer interactions as a network of queues, thereby making it amenable for rapid analysis. We propose novel algorithms that utilize results of this analysis to tune data exchange configurations (event priorities and dropping policies) while meeting situational awareness requirements and resource constraints. FireDeX leverages Software-Defined Networking (SDN) methodologies to enforce these configurations in the IoT network infrastructure. We evaluate its performance through simulated experiments in a smart building fire response scenario. Our results demonstrate significant improvement to mission-critical data delivery under a variety of conditions. Our application-aware prioritization algorithm improves the value of exchanged information by 36% when compared with no prioritization; the addition of our network-aware drop rate policies improves this performance by 42% over priorities only and by 94% over no prioritization

NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use. METHODS: A 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis. RESULTS: Logistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53-0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47-0.56), invasive ventilation (OR: 0.59 95% CI: 0.55-0.64), AKI (OR: 0.67 95% CI: 0.63-0.72), or ECMO (OR: 0.51 95% CI: 0.36-0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations. CONCLUSIONS: Study interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database

A polymorphic transcriptional regulatory domain in the amyotrophic lateral sclerosis risk gene <i>CFAP410</i> correlates with differential isoform expression.

We describe the characterisation of a variable number tandem repeat (VNTR) domain within intron 1 of the amyotrophic lateral sclerosis (ALS) risk gene CFAP410 (Cilia and flagella associated protein 410) (previously known as C21orf2), providing insight into how this domain could support differential gene expression and thus be a modulator of ALS progression or risk. We demonstrated the VNTR was functional in a reporter gene assay in the HEK293 cell line, exhibiting both the properties of an activator domain and a transcriptional start site, and that the differential expression was directed by distinct repeat number in the VNTR. These properties embedded in the VNTR demonstrated the potential for this VNTR to modulate CFAP410 expression. We extrapolated these findings in silico by utilisation of tagging SNPs for the two most common VNTR alleles to establish a correlation with endogenous gene expression. Consistent with in vitro data, CFAP410 isoform expression was found to be variable in the brain. Furthermore, although the number of matched controls was low, there was evidence for one specific isoform being correlated with lower expression in those with ALS. To address if the genotype of the VNTR was associated with ALS risk, we characterised the variation of the CFAP410 VNTR in ALS cases and matched controls by PCR analysis of the VNTR length, defining eight alleles of the VNTR. No significant difference was observed between cases and controls, we noted, however, the cohort was unlikely to contain sufficient power to enable any firm conclusion to be drawn from this analysis. This data demonstrated that the VNTR domain has the potential to modulate CFAP410 expression as a regulatory element that could play a role in its tissue-specific and stimulus-inducible regulation that could impact the mechanism by which CFAP410 is involved in ALS

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or long COVID ), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411

Sex-dependent diversity in ventral tegmental dopaminergic neurons and developmental programing: a molecular, cellular and behavioral analysis

The knowledge that diverse populations of dopaminergic neurons within the ventral tegmental area (VTA) can be distinguished in terms of their molecular, electrophysiological and functional properties, as well as their differential projections to cortical and subcortical regions has significance for key brain functions, such as the regulation of motivation, working memory and sensorimotor control. Almost without exception, this understanding has evolved from landmark studies performed in the male sex. However, converging evidence from both clinical and pre-clinical studies illustrates that the structure and functioning of the VTA dopaminergic systems are intrinsically different in males and females. This may be driven by sex differences in the hormonal environment during adulthood ('activational' effects) and development (perinatal and/or pubertal 'organizational' effects), as well as genetic factors, especially the SRY gene on the Y chromosome in males, which is expressed in a sub-population of adult midbrain dopaminergic neurons. Stress and stress hormones, especially glucocorticoids, are important factors which interact with the VTA dopaminergic systems in order to achieve behavioral adaptation and enable the individual to cope with environmental change. Here, also, there is male/female diversity not only during adulthood, but also in early life when neurobiological programing by stress or glucocorticoid exposure differentially impacts dopaminergic developmental trajectories in male and female brains. This may have enduring consequences for individual resilience or susceptibility to pathophysiological change induced by stressors in later life, with potential translational significance for sex bias commonly found in disorders involving dysfunction of the mesocorticolimbic dopaminergic systems. These findings highlight the urgent need for a better understanding of the sexual dimorphism in the VTA if we are to improve strategies for the prevention and treatment of debilitating conditions which differentially affect men and women in their prevalence and nature, including schizophrenia, attention/deficit hyperactivity disorder, autism spectrum disorders, anxiety, depression and addiction