ALLERGEN IMMUNOTHERAPY: EFFICACY, PERSISTENCE, CONSISTENCY, AND COST EFFECTIVENESS

Although allergen immunotherapy (AIT) has been used for the treatment of allergic rhinitis (AR), allergic conjunctivitis, asthma, stinging insect hypersensitivity, and atopic dermatitis for over 100 years, it has been slow to gain universal acceptance. With the publication of the “World Health Organization Position Paper, Allergen Immunotherapy” in 1998 which summarized the scientific evidence for the efficacy and long-term benefit of this therapy, it has become an accepted and respected modality of treatment. In this review there are discussed following topics of allergen immunotherapy: the reasons for recommending AIT, mechanism of action, subcutaneous and sublingual methods of application, duration, adherence and cost effectiveness. It is necessary to support, not blame, the patient for nonadherence as it is the responsibility of the patient, the physician, and the health-care system to create an environment in which the patient can be adherent. Nonadherence is multifactorial in most every patient and the physician must address all of the factors if adherence is to be improved. The greatest challenge is taking the time to create an individualized patient-tailored strategy to improve adherence, as one size does not fit all. Adherence is dynamic and selecting the best time to start AIT and assuring that there is close follow-up through AIT years of treatment is essential. The patient who is persistent and consistent in year one of AIT may not continue to be so in year three without added encouragement and support. The health-care systems and professional organizations need to help train physicians and their staff both in efficient and accurate ways to assess nonadherence and in implementing interventions to optimize adherence. The multidisciplinary approach to treating this disease of nonadherence will require the involvement of all healthcare professionals, researchers, professional organizations, insurance companies, and policy-makers

Minimal Clinically Important Difference (MCID) in Allergic Rhinitis: Agency for Healthcare Research and Quality or Anchor-Based Thresholds?

BackgroundIn 2013, the Agency for Healthcare Research and Quality (AHRQ) recommended that allergic rhinitis (AR) studies calculate a minimal clinically important difference (MCID) based on an estimated threshold equal to 30% of the maximum total nasal symptom score. Applying this threshold, their data showed no differences between well-established treatments, and a subsequent analysis using prescribing information found no differences between active treatments and placebo controls.ObjectiveThe objective of this study was to demonstrate the application of an evidence-based model to determine MCIDs for AR studies, with an absolute value for an anchor-based threshold and validated methods for calculating distribution-based thresholds.MethodsUsing the same studies as the AHRQ report, anchor- and distribution-based MCID thresholds were determined for 3 clinical comparisons identified by the AHRQ: (1) oral antihistamine+intranasal corticosteroid (INCS) versus INCS, (2) montelukast versus INCS, and (3) intranasal antihistamine+INCS in a single device versus the monotherapies. The outcomes were compared with those reported using the AHRQ threshold.ResultsNo treatment comparison met the AHRQ-defined MCID threshold; all treatments were determined to be equivalent for all 3 queries. In contrast, the evidence-based model revealed some differences between treatments: INCS > montelukast; intranasal antihistamine+INCS > either monotherapy. No clinically relevant benefit was observed for adding an oral antihistamine to INCS, but some studies were not optimal choices for quantitative determination of MCIDs. Updating the literature search revealed no additional studies that met the AHRQ inclusion criteria.ConclusionsThe evidence-based threshold for MCID determination for AR studies should supersede the threshold recommended in the AHRQ report

A plain language summary of what clinical studies can tell us about the safety of evobrutinib – a potential treatment for multiple sclerosis

Immunology; Rheumatology; Systemic lupus erythematosusInmunología; Reumatología; Lupus eritematoso sistémicoImmunologia; Reumatologia; Lupus eritematós sistèmicWhat is this summary about?: This summary explains the findings from a recent investigation that combined the results of over 1000 people from three clinical studies to understand the safety of evobrutinib. Evobrutinib is an oral medication (taken by mouth), being researched as a potential treatment for multiple sclerosis (MS). This medication was also investigated in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Over 1000 people have taken evobrutinib as part of three separate phase 2 clinical studies. These studies looked at how much of the drug should be taken, how safe the drug is, and how well it might work for treating a certain medical condition. What were the results?: Evobrutinib was well-tolerated by participants in all three studies. The number of side effects reported by participants taking the medication was very similar to those reported by participants taking the placebo (a 'dummy' treatment without a real drug). The most common side effects in clinical studies were urinary tract infections, headache, swelling of the nose and throat, diarrhoea and blood markers of potential liver damage (these returned to normal once the treatment was stopped). What do the results mean?: The safety data from all three clinical studies are encouraging and can be used to inform further research into using evobrutinib in MS.X Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS. D Wallace has received consultant fees from Amgen, Celgene, Eli Lilly, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA (an affiliate of Merck KGaA), Janssen and Merck. MC Genovese is an employee of and has financial interests in Gilead. D Tomic is an employee of Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA, and received stock or an ownership interest from Novartis. D Parsons-Rich was an employee of EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, at the time of the study, and is currently an employee of and has received stock from Pfizer. C Le Bolay and H Guehring are employees of Merck Healthcare KGaA, Darmstadt, Germany. A Kao is an employee of and received stock or an ownership interest from EMD Serono Inc., Billerica, MA, USA, a healthcare business of Merck KGaA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported by Merck (CrossRef Funder ID: 10.13039/100009945). This summary was prepared by Lumanity on behalf of, and funded by, Merck KGaA, Darmstadt, Germany

The NASA Solar Cruiser Mission - Solar Sail Propulsion Enabling Heliophysics Missions

Solar Cruiser is a Small Satellite Technology Demonstration Mission (TDM) to mature solar sail propulsion technology to enable near-term, high-priority breakthrough science missions as defined in the Solar and Space Physics Decadal Survey. Solar sails have the potential to provide high ΔV for many types of missions. Solar sails are large, mirror-like structures made of a lightweight material that reflects sunlight to propel the spacecraft. The continuous solar photon pressure provides thrust with no need for the heavy, expendable propellants used by conventional chemical and electric propulsion systems. Solar Cruiser will demonstrate a “sailcraft” platform with pointing control and attitude stability comparable to traditional platforms, upon which a new class of Heliophysics missions may fly. It will show sailcraft operation (acceleration, navigation, station keeping, heliocentric plane change) scalability of sail technologies such as the boom, membrane, and deployer to enable more demanding missions, such as high inclination solar imaging. Solar Cruiser will launch as a secondary payload with NASA’s Interstellar Mapping and Acceleration Probe (IMAP) in early 2025. The sailcraft will separate from the launch vehicle on a near-L1 trajectory (Sun-Earth Lagrangian Point 1; sunward of L1 along the Sun-Earth Line) and complete its primary mission in 11 months or less

Revising evidence of hurricane strikes on Abaco Island (the Bahamas) over the last 700 years

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Winkler, T. S., van Hengstum, P. J., Donnelly, J. P., Wallace, E. J., Sullivan, R. M., MacDonald, D., & Albury, N. A. Revising evidence of hurricane strikes on Abaco Island (the Bahamas) over the last 700 years. Scientific Reports, 10(1), (2020): 16556, doi:10.1038/s41598-020-73132-x.The northern Bahamas have experienced more frequent intense-hurricane impacts than almost anywhere else in the Atlantic since 1850 CE. In 2019, category 5 (Saffir-Simpson scale) Hurricane Dorian demonstrated the destructive potential of these natural hazards. Problematically, determining whether high hurricane activity levels remained constant through time is difficult given the short observational record (< 170 years). We present a 700-year long, near-annually resolved stratigraphic record of hurricane passage near Thatchpoint Blue Hole (TPBH) on Abaco Island, The Bahamas. Using longer sediment cores (888 cm) and more reliable age-control, this study revises and temporally expands a previous study from TPBH that underestimated the sedimentation rate. TPBH records at least 13 ≥ category 2 hurricanes per century between 1500 to 1670 CE, which exceeds the 9 ≥ category 2 hurricanes per century within 50 km of TPBH since 1850 CE. The eastern United States also experienced frequent hurricanes from 1500 to 1670 CE, but frequency was depressed elsewhere in the Atlantic Ocean. This suggests that spatial heterogeneity in Atlantic hurricane activity since 1850 CE could have persisted throughout the last millennium. This heterogeneity is impacted by climatic and stochastic forcing, but additional high-resolution paleo-hurricane reconstructions are required to assess the mechanisms that impact regional variability.Field support was provided by Jody Albury and the staff of Friends of the Environment in Marsh Harbour, The Bahamas, and technical support was provided was provided by M. Horgan and S. Molodtsov. Funding for this project was provided by NSF Awards OCE-1356509, OCE-1356708, OCE-1854917, OCE-1903616, and ICER-1854980. The open access publishing fees for this article have been covered by the Texas A&M University Open Access to Knowledge Fund (OAKFund), supported by the University Libraries

Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity

Sonic hedgehog (Shh) is an indispensable, extrinsic cue that regulates progenitor and stem cell behavior in the developing and adult mammalian central nervous system. Here, we investigate the link between the Shh signaling pathway and Hes1, a classical Notch target. We show that Shh-driven stabilization of Hes1 is independent of Notch signaling and requires the Shh effector Gli2. We identify Gli2 as a primary mediator of this response by showing that Gli2 is required for Hh (Hedgehog)-dependent up-regulation of Hes1. We also show using chromatin immunoprecipitation that Gli2 binds to the Hes1 promoter, which suggests that Hes1 is a Hh-dependent direct target of Gli2 signaling. Finally, we show that Shh stimulation of progenitor proliferation and cell diversification requires Gli2 and Hes1 activity. This paper is the first demonstration of the mechanistic and functional link between Shh, Gli, and Hes1 in the regulation of progenitor cell behavior

Mentoring in Literacy Education: A Commentary from Graduate Students, Untenured Professors, and Tenured Professors

This commentary continues a dialogue which began among literacy teacher educators attending an alternative format session about mentoring in the academy at a national conference. Literacy teacher educators participated in an informal discussion centered on the nature of mentoring in the academy for doctoral students, untenured professors, and tenured professors. Doctoral students focused on their changing identities and roles in the academy, their concerns about navigating the political infrastructure of academia, and the importance of assuming a proactive stance towards obtaining mentoring, especially for part-time doctoral students. Untenured professors focused on the ways they were inventing and reinventing themselves within the power and politics of academia and their need for more holistic mentoring during these turbulent times. Tenured professors were able to embed mentoring experiences into their scholarly work and find ways to benefit or learn from mentoring experiences. These mentors also found comfort in more informal mentoring that included self-initiated endeavors centered on mutual interests. Our commentary draws on these discussions as well as the professional literature on mentoring to describe the importance of mutual trust and reciprocity in mentoring throughout all stages of academia with attention to cultural and linguistic diversity