Vertical and longitudinal electron density structures of equatorial E- and F-regions

From global soundings of ionospheric electron density made with FORMOSAT 3/COSMIC satellites for September 2006–August 2009, day-night variations in vertical and longitudinal structures of the electron densities in equatorial E- and F-regions for different seasons are investigated for the first time. The results reveal that the wavenumber-3 and wavenumber-4 patterns dominated the nighttime (22:00–04:00 LT) F-region longitudinal structures in solstice and in equinox seasons, respectively. In daytime (08:00–18:00 LT) F-region, the wavenumber-4 patterns governed the longitudinal structures in the September equinox and December solstice, and wavenumber-3 in March equinox and June solstice respectively. A comparison of the daytime and nighttime longitudinal electron density structures indicates that they are approximately 180° out of phase with each other. It is believed that this out of phase relation is very likely the result of the opposite phase relation between daytime and nighttime nonmigrating diurnal tidal winds that modulate background E-region dynamo electric field at different places, leading to the day-night change in the locations of the equatorial plasma fountains that are responsible for the formation of the F-region longitudinal structures. Further, a good consistency between the locations of the density structures in the same seasons of the different years for both daytime and nighttime epochs has been noticed indicating that the source mechanism for these structures could be the same

A comparison of five paediatric dosing guidelines for antibiotics

Objective: To compare dosing guidance in the paediatric formularies of high- and middle-income countries for 32 commonly prescribed antibiotics on the World Health Organization's (WHO's) 2017 Model list of essential medicines for children. / Methods: We identified paediatric antibiotic guidelines that were either widely used internationally or originated from countries in which antibiotic use has increased markedly in recent years (i.e. Brazil, China, India, the Russian Federation and South Africa). / Findings: The study analysis considered five leading antibiotic guidelines: (i) the Manual of childhood infections: the blue book; (ii) the BNF (British national formulary) for children; (iii) the Red book®: 2018-2021 report of the committee on infectious diseases; (iv) WHO's Pocket book of hospital care for children; and (v) Indian National treatment guidelines for antimicrobial use in infectious diseases. There was marked heterogeneity in the recommended dosing (i.e. daily dose, age dosing bands and dose frequency) for most commonly used antibiotics. The rationale for dosing recommendations was generally unclear. / Conclusion: The pharmacokinetic, pharmacodynamic and clinical evidence supporting paediatric antibiotic dosing, particularly on total doses and on age or weight dosing bands, needs to be improved. Future research should consider whether the variations in guidance identified stem from different clinical disease patterns, varying levels of antibiotic resistance or drug availability rather than historical preferences. Interested global parties could collaborate with WHO's Model list of essential medicines antibiotic working group to develop an evidence-based consensus and identify research priorities

Averages of Fourier coefficients of Siegel modular forms and representation of binary quadratic forms by quadratic forms in four variables

Let $-d$ be a a negative discriminant and let $T$ vary over a set of representatives of the integral equivalence classes of integral binary quadratic forms of discriminant $-d$. We prove an asymptotic formula for $d \to \infty$ for the average over $T$ of the number of representations of $T$ by an integral positive definite quaternary quadratic form and obtain results on averages of Fourier coefficients of linear combinations of Siegel theta series. We also find an asymptotic bound from below on the number of binary forms of fixed discriminant $-d$ which are represented by a given quaternary form. In particular, we can show that for growing $d$ a positive proportion of the binary quadratic forms of discriminant $-d$ is represented by the given quaternary quadratic form.Comment: v5: Some typos correcte

Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen

Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: The PREVENT-HD study

© 2021 Elsevier Inc. Background: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established. Study Design: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events. Conclusions: PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19

Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study

Objective To evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA). Methods This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses. Results Of 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24). Conclusions At week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis

Flexible and Stretchable Self-Powered Multi-Sensors Based on the N-Type Thermoelectric Response of Polyurethane/Na-x(Ni-ett)(n) Composites

Flexible and stretchable electronic devices have a broad range of potential uses, from biomedicine, soft robotics, and health monitoring to the internet‐of‐things. Unfortunately, finding a robust and reliable power source remains challenging, particularly in off‐the‐grid and maintenance‐free applications. A sought‐after development overcome this challenge is the development of autonomous, self‐powered devices. A potential solution is reported exploiting a promising n‐type thermoelectric compound, poly nickel‐ethenetetrathiolates (Na_{x}(Ni‐ett)_{n}). Highly stretchable n‐type composite films are obtained by combining Nax(Ni‐ett)n with commercial polyurethane (Lycra). As high as 50 wt% Na_{x}(Ni‐ett)_{n} content composite film can withstand deformations of ≈500% and show conductivities of ≈10^{-2} S cm^{-1} and Seebeck coefficients of approx. −40 µV K^{-1}. These novel materials can be easily synthesized on a large scale with continuous processes. When subjected to a small temperature difference (<20 °C), the films generate sufficient thermopower to be used for sensing strain (gauge factor ≈20) and visible light (sensitivity factor ≈36% (kW m^{-2})^{-1}), independent of humidity (sensitivity factor ≈0.1 (%RH)^{-1}. As a proof‐of‐concept, a wearable self‐powered sensor is demonstrated by using n‐type Na_{x}(Ni‐ett)_{n}/Lycra and PEDOT:PSS/Lycra elements, connected in series by hot pressing, without employing any metal connections, hence preserving good mechanical ductility and ease of processing

Photodynamic Therapy with the Silicon Phthalocyanine Pc 4 Induces Apoptosis in Mycosis Fungoides and Sezary Syndrome

Our current focus on the effects of Photodynamic Therapy (PDT) using silicon phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to preclinical observations that Jurkat cells, common surrogate for human T cell lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid carcinoma A431 cells. Mycosis fungoides (MF) as well as Sezary syndrome (SS) are variants of cutaneous T-cell lymphoma (CTCL) in which malignant T-cells invade the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in peripheral blood cells obtained from patients with SS and in skin biopsies of patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis of CD4+CD7− malignant T-lymphocytes in the blood relative to CD11b+ monocytes and nonmalignant T-cells. In vivo Pc 4-PDT of MF skin also photodamages the antiapoptotic protein Bcl-2

Efficacy and safety of rociletinib versus chemotherapy in patients with EGFR-mutated NSCLC: the results of TIGER-3, a phase 3 randomized study

Introduction: The TIGER-3 (NCT02322281) study was initiated to compare the efficacy and safety of rociletinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets EGFR T790M and common EGFR-activating mutations, versus chemotherapy in patients with NSCLC who progressed on first- or second-generation EGFR TKIs. Methods: Patients with advanced or metastatic EGFR-mutated NSCLC with disease progression on standard therapy (previous EGFR TKI and platinum-based chemotherapy) were randomized to oral rociletinib (500 or 625 mg twice daily) or single-agent chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel). Results: Enrollment was halted when rociletinib development was discontinued in 2016. Of 149 enrolled patients, 75 were randomized to rociletinib (n = 53: 500 mg twice daily; n = 22: 625 mg twice daily) and 74 to chemotherapy. The median investigator-assessed progression-free survival (PFS) was 4.1 months (95% confidence interval [CI]: 2.6-5.4) in the rociletinib 500-mg group and 5.5 months (95% CI: 1.8-8.1) in the 625-mg group versus 2.5 months (95% CI: 1.4-2.9) in the chemotherapy group. An improved PFS was observed in patients with T790M-positive NSCLC treated with rociletinib (n = 25; 500 mg and 625 mg twice daily) versus chemotherapy (n = 20; 6.8 versus 2.7 mo; hazard ratio = 0.55, 95% CI: 0.28-1.07, p = 0.074). Grade 3 or higher hyperglycemia (24.0%), corrected QT prolongation (6.7%), diarrhea (2.7%), and vomiting (1.3%) were more frequent with rociletinib than chemotherapy (0%, 0%, 1.4%, and 0%, respectively). Conclusions: Rociletinib had a more favorable median PFS versus chemotherapy but had higher rates of hyperglycemia and corrected QT prolongation in patients with advanced EGFR-mutated NSCLC who progressed on previous EGFR TKI. Incomplete enrollment prevented evaluation of the primary efficacy end point