Clinically meaningful responses to dupilumab among children aged 6 months to 5 years with moderate-to-severe atopic dermatitis who did not achieve clear or almost clear skin according to the investigator’s global assessment: a post hoc analysis of a phase 3 trial

In young children, atopic dermatitis (AD) imposes a multidimensional burden on many aspects of their quality of life (QoL) and that of their families. LIBERTY AD PRESCHOOL part B was a randomized, double- blinded, placebo-controlled phase 3 trial in 162 children (aged 6 months to 5 years) with moderate-to- severe AD receiving dupilumab or placebo, plus low-potency topical corticosteroids. Post hoc analyses were performed on the full analysis set (FAS) and a subset of patients with Investigator’s Global Assessment score > 1 at week 16. The primary outcome was the proportion of patients at week 16 achieving a composite endpoint encompassing clinically meaningful changes in AD signs, symptoms and QoL: ≥ 50% improvement in Eczema Area and Severity Index; and/or ≥ 4-point reduction in worst scratch/itch numerical rating scale; and/or ≥ 6-point reduction in Children’s Dermatology Life Quality Index/Infants’ Dermatitis Quality of Life Index. Significantly more patients receiving dupilumab vs placebo achieved the composite endpoint in both the FAS (77.7% vs 24.6%, p < 0.0001) and subgroup (68.9% vs 21.5%, p < 0.0001). Dupilumab provided rapid and significant, clinically meaningful improvements in AD signs, symptoms, and QoL in the overall group and subgroup of patients who did not achieve clear or almost clear skin at week 16

Large-scale Bright Fronts in the Solar Corona: A Review of "EIT waves"

``EIT waves" are large-scale coronal bright fronts (CBFs) that were first observed in 195 \AA\ images obtained using the Extreme-ultraviolet Imaging Telescope (EIT) onboard the \emph{Solar and Heliospheric Observatory (SOHO)}. Commonly called ``EIT waves", CBFs typically appear as diffuse fronts that propagate pseudo-radially across the solar disk at velocities of 100--700 km s$^{-1}$ with front widths of 50-100 Mm. As their speed is greater than the quiet coronal sound speed ($c_s\leq$200 km s$^{-1}$) and comparable to the local Alfv\'{e}n speed ($v_A\leq$1000 km s$^{-1}$), they were initially interpreted as fast-mode magnetoacoustic waves ($v_{f}=(c_s^2 + v_A^2)^{1/2}$). Their propagation is now known to be modified by regions where the magnetosonic sound speed varies, such as active regions and coronal holes, but there is also evidence for stationary CBFs at coronal hole boundaries. The latter has led to the suggestion that they may be a manifestation of a processes such as Joule heating or magnetic reconnection, rather than a wave-related phenomena. While the general morphological and kinematic properties of CBFs and their association with coronal mass ejections have now been well described, there are many questions regarding their excitation and propagation. In particular, the theoretical interpretation of these enigmatic events as magnetohydrodynamic waves or due to changes in magnetic topology remains the topic of much debate.Comment: 34 pages, 19 figure

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Soil Organic Carbon Isotope Tracing in Sorghum under Ambient CO2 and Free-Air CO2 Enrichment (FACE)

As atmospheric carbon dioxide concentrations, [CO2Air ], continue their uncontrolled rise, the capacity of soils to accumulate or retain carbon is uncertain. Free-air CO2 enrichment (FACE) experiments have been conducted to better understand the plant, soil and ecosystem response to elevated [CO2 ], frequently employing commercial CO2 that imparts a distinct isotopic signal to the system for tracing carbon. We conducted a FACE experiment in 1998 and 1999, whereby sorghum (C4 photosynthetic pathway) was grown in four replicates of four treatments using a split-strip plot design: (i) ambient CO2 /ample water (365 µmol mol−1, “Control–Wet”), (ii) ambient CO2 /water stress (“Control–Dry”), (iii) CO2-enriched (560 µmol mol−1, “FACE–Wet”), and (iv) CO2-enriched/water stressed (“FACE–Dry”). The stable-carbon isotope composition of the added CO2 (in FACE treatments) was close to that of free atmosphere background values, so the subsequent similar13 C-enriched carbon signal photosynthetically fixed by C4 sorghum plants could be used to trace the fate of carbon in both FACE and control treatments. Measurement of soil organic carbon content (SOC (%) = gC/ gdry soil × 100%) and δ13 C at three depths (0–15, 15–30, and 30–60 cm) were made on soils from the beginning and end of the two experimental growing seasons. A progressive ca. 0.5‰–1.0‰ δ13 C increase in the upper soil SOC in all treatments over the course of the experiment indicated common entry of new sorghum carbon into the SOC pools. The 0–15 cm SOC in FACE treatments was13 C-enriched relative to the Control by ca. 1‰, and according to isotopic mass balance, the fraction of the new sorghum-derived SOC in the Control–Wet treatment at the end of the second season was 8.4%, 14.2% in FACE–Wet, 6.5% in Control–Dry, and 14.2% in FACE–Dry. The net SOC enhancement resulting from CO2 enrichment was therefore 5.8% (or 2.9% y−1 of experiment) under ample water and 7.7% (3.8% y−1 of experiment) under limited water, which matches the pattern of greater aboveground biomass increase with elevated [CO2Air ] under the Dry treatment, but no parallel isotopic shifts were found in deeper soils. However, these increased fractions of new carbon in SOC at the end of the experiment do not necessarily mean an increase in total SOC content, because gravimetric measurements of SOC did not reveal a significant increase under elevated [CO2Air ], at least within the limits of SOC-content error bars. Thus, new carbon gains might be offset by pre-experiment carbon losses. The results demonstrate successful isotopic tracing of carbon from plants to soils in this sorghum FACE experiment showing differences between FACE and Control treatments, which suggest more dynamic cycling of SOC under elevated [CO2Air ] than in the Control treatment. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Disability in multiple sclerosis is related to thalamic connectivity and cortical network atrophy

Background: Thalamic atrophy is proposed to be a major predictor of disability progression in multiple sclerosis (MS), while thalamic function remains understudied. Objectives: To study how thalamic functional connectivity (FC) is related to disability and thalamic or cortical network atrophy in two large MS cohorts. Methods: Structural and resting-state functional magnetic resonance imaging (fMRI) was obtained in 673 subjects from Amsterdam (MS: N = 332, healthy controls (HC): N = 96) and Graz (MS: N = 180, HC: N = 65) with comparable protocols, including disability measurements in MS (Expanded Disability Status Scale, EDSS). Atrophy was measured for the thalamus and seven well-recognized resting-state networks. Static and dynamic thalamic FC with these networks was correlated with disability. Significant correlates were included in a backward multivariate regression model. Results: Disability was most strongly related (adjusted R 2 = 0.57, p < 0.001) to higher age, a progressive phenotype, thalamic atrophy and increased static thalamic FC with the sensorimotor network (SMN). Static thalamus–SMN FC was significantly higher in patients with high disability (EDSS ⩾ 4) and related to network atrophy but not thalamic atrophy or lesion volumes. Conclusion: The severity of disability in MS was related to increased static thalamic FC with the SMN. Thalamic FC changes were only related to cortical network atrophy, but not to thalamic atrophy