T-bet controls severity of hypersensitivity pneumonitis

Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation and in some patients' fibrosis. IFNγ plays a critical role in HP; in the absence of IFNγ granuloma formation does not occur. However, recent studies using animal models of HP have suggested that HP is a Th17 disease calling into question the role of IFNγ. In this study, we report that initially IFNγ production is dependent on IL-18 and the transcription factor T-bet, however as the disease continues IFNγ production is IL-18-independent and partially T-bet dependent. Although IFNγ production is required for granuloma formation its role is distinct from that of T-bet. Mice that are deficient in T-bet and exposed to S. rectivirgula develop more severe disease characterized by an exacerbated Th17 cell response, decreased Th1 cell response, and increased collagen production in the lung. T-bet-mediated protection does not appear to be due to the development of a protective Th1 response; shifting the balance from a Th17 predominant response to a Th1 response by inhibition of IL-6 also results in lung pathology. The results from this study suggest that both Th1 and Th17 cells can be pathogenic in this model and that IFNγ and T-bet play divergent roles in the disease process

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Models of classroom assessment for course-based research experiences

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education

Culturally Responsive Framework to Address Gambling Related Harm

This report presents a Culturally Responsive Framework to Address Gambling Related Harm (herein referred to as the Framework) based on the findings of participatory action research. The purpose of the Framework is to enhance the capacity of the multi-sectorial human service system to provide appropriate and effective responses at the systemic, organisational, professional, and individual levels. It seeks to strengthen practice, increase accessibility, provide options and tools for implementation and contribute to the evidence base underpinning best practice

From first to latest imaging technology: Revisiting the first mummy investigated with X-ray in 1896 by using dual-source computed tomography

Purpose The aim of this study was to systematically reinvestigate the first human mummy that was ever analyzed with X-ray imaging in 1896, using dual-source computed tomography (DSCT) in order to compare the earliest and latest imaging technologies, to estimate preservation, age at death, sex, anatomical variants, paleopathological findings, mummification, embalming and wrapping of the child mummy from ancient Egypt. Radiocarbon dating was used to determine the mummy’s age and to specify the child’s living period in the Egyptian chronology. Material and methods The ancient Egyptian child mummy is kept in the Senckenberg Museum of Natural History in Frankfurt am Main, Germany. An accelerator mass spectrometer (MICADAS) was used for radiocarbon dating. DSCT was performed using a 2 × 64 slice dual-source CT system (Siemens Healthineers, Forchheim, Germany). A thorough visual examination of the mummy, a systematic radiological evaluation of the DICOM datasets, and established methods in physical anthropology were applied to assess the bio-anthropological data and the post mortem treatment of the body. Results: Radiocarbon dating yielded a calibrated age between 378 and 235 cal BC (95.4% confidence interval), corresponding with the beginning of the Ptolemaic period. The mummy was a male who was four to five years old at the time of death. Remnants of the brain and inner organs were preserved by the embalmers, which is regularly observed in ancient Egyptian child mummies. Skin tissue, inner organs, tendons and/or musculature, cartilage, nerves and vasculature could be identified on the DSCT dataset. The dental health of the child was excellent. Anatomical variants and pathological defects included a congenital Pectus excavatum deformity, hepatomegaly, Harris lines, and longitudinal clefts in the ventral cortices of both femora. Conclusion: Our results highlight the enormous progress achieved form earliest to latest imaging technology for advanced mummy research using the first human mummy investigated with X-ray. With the application of DSCT, detailed knowledge regarding age at death, sex, diseases, death, and mummification of a child from Ptolemaic Egypt are revealed while considering the temporary rites of body treatment and burial for children

N-Aryl Arenedicarboximides as Tunable Panchromatic Dyes for Molecular Solar Cells

Three organic dyes designed as molecular dyads were prepared that feature a common naphthalimide acceptor and N-aryl donors. One of these incorporated an additional cyanoacrylic acid linker and conjugated thiophene bridge inserted between donor and acceptor groups. Electrochemical and photochemical characterizations have been carried out on nanocrystalline TiO2 dye-sensitized solar cells which were fabricated with these dyes as the sensitizing component. HOMO and LUMO energies were also calculated using TDDFT methods and validated by the cyclic voltammetry method. A key finding from this study indicates that computational methods can provide energy values in close agreement to experimental for the N-aryl-naphthalimide system. Relative to HOMO/LUMO energy levels of N719, the dyes based on naphthalimide chromophore are promising candidates for metal-free DSSCs