525 research outputs found

    What Does it Mean to be a British Isles Lupus Assessment Group-Based Composite Lupus Assessment Responder? Post Hoc Analysis of 2 Phase 3 Trials

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    OBJECTIVE: The British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) is a validated global measure of treatment response in systemic lupus erythematosus (SLE) clinical trials. To understand the relevance of BICLA in clinical practice, we investigated relationships between BICLA response and routine SLE assessments, patient-reported outcomes (PROs), and medical resource utilization. METHODS: This was a post hoc analysis of pooled data from the phase III, randomized, placebo-controlled, 52-week TULIP-1 (ClinicalTrials.gov identifier: NCT02446912; n = 457) and TULIP-2 (ClinicalTrials.gov identifier: NCT02446899; n = 362) trials of intravenous anifrolumab (150/300 mg once every 4 weeks) in patients with moderate-to-severe SLE. Changes from baseline to week 52 in clinical assessments, PROs, and medical resource use were compared in BICLA responders versus nonresponders, regardless of treatment assignment. RESULTS: BICLA responders (n = 318) achieved significantly improved outcomes compared with nonresponders (n = 501), including lower flare rates, higher rates of attainment of sustained oral glucocorticoid taper to ≤7.5 mg/day, greater improvements in PROs (Functional Assessment of Chronic Illness Therapy–Fatigue, Short Form 36 Health Survey), and fewer SLE-related hospitalizations/emergency department visits (all nominal P < 0.001). Compared with nonresponders, BICLA responders had greater improvements in global and organ-specific disease activity (Physician’s Global Assessment, SLE Disease Activity Index 2000, Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity, and joint counts; all nominal P < 0.001). BICLA responders had fewer lupus-related serious adverse events than nonresponders. CONCLUSION: BICLA response is associated with clinical benefit in SLE assessments, PROs, and medical resource utilization, confirming its value as a clinical trial end point that is associated with measures important to patient care

    Hyperbolic positioning method using broadcast digital television signals and monitor receiver ranging

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    PatentA system and method involve determining a time difference of arrival between two robust broadcast digital television (DTV) signals received at a mobile receiver and a monitor receiver from at least two DTV transmitters, determining a pseudorange between the mobile receiver and each of the DTV transmitters, and determining a position of the mobile receiver using the determinedpseudoranges and the distance between the monitor receiver and the mobile receiver

    Dual‐Sensitivity Multiple Sclerosis Lesion and CSF Segmentation for Multichannel 3T Brain MRI

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    ABSTRACT BACKGROUND AND PURPOSE A pipeline for fully automated segmentation of 3T brain MRI scans in multiple sclerosis (MS) is presented. This 3T morphometry (3TM) pipeline provides indicators of MS disease progression from multichannel datasets with high‐resolution 3‐dimensional T1‐weighted, T2‐weighted, and fluid‐attenuated inversion‐recovery (FLAIR) contrast. 3TM segments white (WM) and gray matter (GM) and cerebrospinal fluid (CSF) to assess atrophy and provides WM lesion (WML) volume. METHODS To address nonuniform distribution of noise/contrast (eg, posterior fossa in 3D‐FLAIR) of 3T magnetic resonance imaging, the method employs dual sensitivity (different sensitivities for lesion detection in predefined regions). We tested this approach by assigning different sensitivities to supratentorial and infratentorial regions, and validated the segmentation for accuracy against manual delineation, and for precision in scan‐rescans. RESULTS Intraclass correlation coefficients of .95, .91, and .86 were observed for WML and CSF segmentation accuracy and brain parenchymal fraction (BPF). Dual sensitivity significantly reduced infratentorial false‐positive WMLs, affording increases in global sensitivity without decreasing specificity. Scan‐rescan yielded coefficients of variation (COVs) of 8% and .4% for WMLs and BPF and COVs of .8%, 1%, and 2% for GM, WM, and CSF volumes. WML volume difference/precision was .49 ± .72 mL over a range of 0–24 mL. Correlation between BPF and age was r = .62 (P = .0004), and effect size for detecting brain atrophy was Cohen's d = 1.26 (standardized mean difference vs. healthy controls). CONCLUSIONS This pipeline produces probability maps for brain lesions and tissue classes, facilitating expert review/correction and may provide high throughput, efficient characterization of MS in large datasets

    Diet modulates the relationship between immune gene expression and functional immune responses

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    Nutrition is vital to health and the availability of resources has long been acknowledged as a key factor in the ability to fight off parasites, as investing in the immune system is costly. Resources have typically been considered as something of a "black box", with the quantity of available food being used as a proxy for resource limitation. However, food is a complex mixture of macro- and micronutrients, the precise balance of which determines an animal's fitness. Here we use a state-space modelling approach, the Geometric Framework for Nutrition (GFN), to assess for the first time, how the balance and amount of nutrients affects an animal's ability to mount an immune response to a pathogenic infection. Spodoptera littoralis caterpillars were assigned to one of 20 diets that varied in the ratio of macronutrients (protein and carbohydrate) and their calorie content to cover a large region of nutrient space. Caterpillars were then handled or injected with either live or dead Xenorhabdus nematophila bacterial cells. The expression of nine genes (5 immune, 4 non-immune) was measured 20 h post immune challenge. For two of the immune genes (PPO and Lysozyme) we also measured the relevant functional immune response in the haemolymph. Gene expression and functional immune responses were then mapped against nutritional intake. The expression of all immune genes was up-regulated by injection with dead bacteria, but only those in the IMD pathway (Moricin and Relish) were substantially up-regulated by both dead and live bacterial challenge. Functional immune responses increased with the protein content of the diet but the expression of immune genes was much less predictable. Our results indicate that diet does play an important role in the ability of an animal to mount an adequate immune response, with the availability of protein being the most important predictor of the functional (physiological) immune response. Importantly, however, immune gene expression responds quite differently to functional immunity and we would caution against using gene expression as a proxy for immune investment, as it is unlikely to be reliable indicator of the immune response, except under specific dietary conditions. [Abstract copyright: Copyright © 2019. Published by Elsevier Ltd.

    Effectiveness of Fluorography Versus Cineangiography at Reducing Radiation Exposure During Diagnostic Coronary Angiography

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    Coronary angiography is the gold standard for defining obstructive coronary disease. However, radiation exposure remains an unwanted hazard. Patients referred for coronary angiography with abdominal circumference60 ml/min were randomized to the fluorography (n = 25) or cineangiography (n = 25) group. Patients in the fluorography group underwent coronary angiography using retrospectively stored fluorography with repeat injection under cineangiography only when needed for better resolution per operator\u27s discretion. Patients in the cineangiography group underwent coronary angiography using routine cineangiography. The primary end point was patient radiation exposure measured by radiochromic film. Secondary end points included the radiation output measurement of kerma-area product and air kerma at the interventional reference point (Ka,r) and operator radiation exposure measured by a dosimeter. Patient radiation exposure (158.2 mGy [76.5 to 210.2] vs 272.5 mGy [163.3 to 314.0], p = 0.001), kerma-area product (1,323 mu Gy.m(2) 1826 to 1,765] vs 3,451 mu Gy.m(2) [2,464 to 4,818], p \u3c 0.001), and Ka,r (175 mGy [112 to 252] vs 558 mGy [313 to 621], p \u3c 0.001) were significantly lower in the fluorography compared with cineangiography group (42%, 62%, and 69% relative reduction, respectively). Operator radiation exposure trended in the same direction, although statistically nonsignificant (fluorography 2.35 mu Gy [1.24 to 6.30] vs cineangiography 5,03 mu Gy 12.48 to 7.80], p = 0.059). In conclusion, the use of fluorography in a select group of patients during coronary angiography, with repeat injection under cineangiography only when needed, was efficacious at reducing patient radiation exposure. (C) 2014 Elsevier Inc. All rights reserved

    The transition from diet to blood: Exploring homeostasis in the insect haemolymph nutrient pool

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    Nutrition is vital to health, but while the link between diet and body nutritional composition is well explored in humans and other vertebrates, this information is not well understood in insects, despite the vital roles they play in ecosystems, and their increasing use as experimental models. Here we used Nutritional Geometry to explore the rapid physiological response to ingested nutrients in the haemolymph nutritional profile of Spodoptera littoralis caterpillars. We ask whether blood nutrients are maintained homeostatically in the face of variable nutritional intake, or if regulation is more flexible for some nutrients than others (allostasis), which allows animals to adapt to stress by responding in a way that prioritises efficiency of responses in the face of trade‐offs. Caterpillars were placed on 1 of 20 diets, systematically varying in their nutrient ratios (protein: carbohydrate) and density (calorie content), and their consumption was measured. After 48 h, caterpillars were bled, and the macronutrient (protein, carbohydrates and lipids) and nutrient metabolite (amino acids and simple sugars) content of the haemolymph was measured. Proteins comprised 93% of the haemolymph macronutrient pool on average and their concentration increased with protein eaten. The amino acid (AA) pool was dominated by five AAs, and the total pool increased with total nutrient intake. However, the ratio of essential to non‐essential AAs increased as the proportion of protein consumed increased. Carbohydrates were tightly controlled, increasing only on the most extreme carbohydrate intakes. Simple sugars were dominated by glucose and trehalose, and overall, the simple sugar pool showed high levels of homeostasis. Rather than strict homeostasis of blood nutritional properties, an allostatic model seemed to be a better fit for blood nutrient regulation in this generalist herbivore. This flexibility in response to the nutritional composition of the diet may, in part, explain how this species has evolved to extreme dietary generalism and may play a role in its worldwide pest status. Given the range of fitness‐related processes affected by the haemolymph, future studies should examine the physiological impacts of blood nutrient variation on reproduction, growth and response to infection and the trade‐offs between them

    Interaction between dislocation and coherent twin boundary by quasicontinuum model

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    The interaction between lattice dislocations and Coherent Twin Boundary Σ3{111} of copper has been studied using Quasi-Continuum method. The coherent twin boundary provides high barrier to slip transmission. The dislocation pile-up modifies the stress field at its intersection with the grain boundary. A different reaction process compared with the case of single dislocations is noticed. One observes the nucleation of a Lomer-type dislocation with Burgers vector of ½ and its glide on the (100) cube plane in the adjacent grain. This phenomenon has been observed with Transmission Electron Microscopy at room temperature and in other Molecular Dynamics simulations. We also show a novel interaction mechanism between Lomer-type dislocation and Coherent Twin Boundary. This interaction process leaves a dislocation with a Burgers vector coincident with the complete lattice shift of the Coherent Twin Boundary. Quantitative estimation of critical stress for various transmission phenomena is performed by using irial stress. Such information can be used as input for Discrete Dislocation Dynamics model

    Germline heterozygous DDX41 variants in a subset of familial myelodysplasia and acute myeloid leukemia

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    The Brazilian National Council for Scientific and Technological Development), Bloodwise, Children with Cancer and MRC (Medical Research Council, UK)
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