A survey of the treatment and management of patients with severe chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is characterized by the recurrent appearance of weals, angio‐oedema or both, occurring at least twice weekly for longer than 6 weeks.1 It is often managed with antihistamines, but occasionally requires other systemic agents in recalcitrant cases. A cross‐sectional survey was conducted by means of an internet‐based survey tool (Typeform; https://www.typeform.com). Participating consultants with a specialist interest in urticaria were identified through the specialist registers of the British Society of Allergy and Clinical Immunology (BSACI), the Improving Quality in Allergy Services (IQAS) Group and the British Association of Dermatologists (BAD), and invited to take part. The survey content was based on current CSU treatment guidelines from EAACI/GA2LEN/EDF/WAO1 and the British Society for Allergy and Clinical Immunology (BSACI).2 The EAACI/GA2LEN/EDF/WAO guidelines are a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN) (a European Union‐funded network of excellence), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO). To standardize responses, all participants were presented with a case of recalcitrant CSU (failed on maximum dose of nonsedating antihistamines and montelukast), requiring alternative systemic treatment. Questions covered usage of systemic treatments, routine disease severity assessments, adherence to treatment guidelines and perceived barriers to prescribing. Responses (Table 1) were received from 19 UK consultants (26 surveys sent; completion rate 73%), 15 of whom had > 10 years’ experience in the treatment of CSU. The majority were allergy (58%) and dermatology consultants (37%). Of the 19 consultants, 56% provide a dedicated urticaria service, 37% treat both adult and paediatric patients, and the majority (79%) use systemic medications other than antihistamines and montelukast. Omalizumab and ciclosporin were the most commonly used first‐line agents (47% and 27% respectively) (Fig. 1). The majority (84%) of consultants use validated measures to assess disease severity, including the weekly Urticaria Activity Score (UAS‐7, 63%), the Physician Global Assessment (63%), the Patient Global Assessment (44%) and the Dermatology Quality of Life Index (DLQI) (38%). Guidelines are used by 89% to direct their management of CSU, with 50% using the EAACI/GA2LEN/EDF/WAO guideline,1 compared with 31% primarily using the BSACI guideline.2 The main perceived barriers to prescribing systemic medications were potential adverse effects (AEs) (32% strongly agreed), potential long‐term toxicity (26% strongly agreed), cost of treatment (42% strongly agreed), and views expressed by the patient and their family (37% agreed)

An eHealth capabilities framework for graduates and health professionals: Mixed-methods study

© Melissa Brunner, Deborah McGregor, Melanie Keep, Anna Janssen, Heiko Spallek, Deleana Quinn, Aaron Jones, Emma Tseris, Wilson Yeung, Leanne Togher, Annette Solman, Tim Shaw. Background: The demand for an eHealth-ready and adaptable workforce is placing increasing pressure on universities to deliver eHealth education. At present, eHealth education is largely focused on components of eHealth rather than considering a curriculum-wide approach. Objective: This study aimed to develop a framework that could be used to guide health curriculum design based on current evidence, and stakeholder perceptions of eHealth capabilities expected of tertiary health graduates. Methods: A 3-phase, mixed-methods approach incorporated the results of a literature review, focus groups, and a Delphi process to develop a framework of eHealth capability statements. Results: Participants (N=39) with expertise or experience in eHealth education, practice, or policy provided feedback on the proposed framework, and following the fourth iteration of this process, consensus was achieved. The final framework consisted of 4 higher-level capability statements that describe the learning outcomes expected of university graduates across the domains of (1) digital health technologies, systems, and policies; (2) clinical practice; (3) data analysis and knowledge creation; and (4) technology implementation and codesign. Across the capability statements are 40 performance cues that provide examples of how these capabilities might be demonstrated. Conclusions: The results of this study inform a cross-faculty eHealth curriculum that aligns with workforce expectations. There is a need for educational curriculum to reinforce existing eHealth capabilities, adapt existing capabilities to make them transferable to novel eHealth contexts, and introduce new learning opportunities for interactions with technologies within education and practice encounters. As such, the capability framework developed may assist in the application of eHealth by emerging and existing health care professionals. Future research needs to explore the potential for integration of findings into workforce development programs

Seasonal cycle of precipitation variability in South America on intraseasonal timescales

The seasonal cycle of the intraseasonal (IS) variability of precipitation in South America is described through the analysis of bandpass filtered outgoing longwave radiation (OLR) anomalies. The analysis is discriminated between short (10--30 days) and long (30--90 days) intraseasonal timescales. The seasonal cycle of the 30--90-day IS variability can be well described by the activity of first leading pattern (EOF1) computed separately for the wet season (October--April) and the dry season (May--September). In agreement with previous works, the EOF1 spatial distribution during the wet season is that of a dipole with centers of actions in the South Atlantic Convergence Zone (SACZ) and southeastern South America (SESA), while during the dry season, only the last center is discernible. In both seasons, the pattern is highly influenced by the activity of the Madden--Julian Oscillation (MJO). Moreover, EOF1 is related with a tropical zonal-wavenumber-1 structure superposed with coherent wave trains extended along the South Pacific during the wet season, while during the dry season the wavenumber-1 structure is not observed. The 10--30-day IS variability of OLR in South America can be well represented by the activity of the EOF1 computed through considering all seasons together, a dipole but with the stronger center located over SESA. While the convection activity at the tropical band does not seem to influence its activity, there are evidences that the atmospheric variability at subtropical-extratropical regions might have a role. Subpolar wavetrains are observed in the Pacific throughout the year and less intense during DJF, while a path of wave energy dispersion along a subtropical wavetrain also characterizes the other seasons. Further work is needed to identify the sources of the 10--30-day-IS variability in South America

Ibrutinib restores immune cell numbers and function in first-line and relapsed/refractory chronic lymphocytic leukemia

© 2020 The Authors Ibrutinib positively modulates many T-cell subsets in chronic lymphocytic leukemia (CLL). To understand ibrutinib\u27s effects on the broader landscape of immune cell populations, we comprehensively characterized changes in circulating counts of 21 immune blood cell subsets throughout the first year of treatment in patients with relapsed/refractory (R/R) CLL (n = 55, RESONATE) and previously untreated CLL (n = 50, RESONATE-2) compared with untreated age-matched healthy donors (n = 20). Ibrutinib normalized abnormal immune cell counts to levels similar to those of age-matched healthy donors. Ibrutinib significantly decreased pathologically high circulating B cells, regulatory T cells, effector/memory CD4+ and CD8+ T cells (including exhausted and chronically activated T cells), natural killer (NK) T cells, and myeloid-derived suppressor cells; preserved naive T cells and NK cells; and increased circulating classical monocytes. T-cell function was assessed in response to T-cell receptor stimulation in patients with R/R CLL (n = 21) compared with age-matched healthy donors (n = 18). Ibrutinib significantly restored T-cell proliferative ability, degranulation, and cytokine secretion. Over the same period, ofatumumab or chlorambucil did not confer the same spectrum of normalization as ibrutinib in multiple immune subsets. These results establish that ibrutinib has a significant and likely positive impact on circulating malignant and nonmalignant immune cells and restores healthy T-cell function

Prophylactic Intra-Aortic Balloon Counterpulsation in High Risk Cardiac Surgery: The PINBALL Pilot Multicentre, Registry-Linked, Randomised, Controlled Feasibility Trial

Background: Prophylactic intra-aortic balloon counterpulsation (IABC) is commonly used in selected patients undergoing coronary artery bypass graft (CABG) surgery, but definitive evidence is lacking. The aim of the multicentre PINBALL Pilot randomised controlled trial (RCT) was to assess the feasibility of performing a definitive trial to address this question. Methods: Patients listed for CABG surgery with impaired left ventricular function and at least one additional risk factor for postoperative low cardiac output syndrome were eligible for inclusion if the treating surgical team was uncertain as to the benefit of prophylactic IABC. The primary outcome of feasibility was based on exceeding a pre-specified recruitment rate, protocol compliance and follow-up. Results: The recruitment rate of 0.5 participants per site per month did not meet the feasibility threshold of two participants per site per month and the study was stopped early after enrolment of 24 out of the planned sample size of 40 participants. For 20/24 (83%) participants, preoperative IABC use occurred according to study assignment. Six (6)-month follow-up was available for all enrolled participants, [IABC 1 death (8%) vs. control 1 death (9%), p = 0.95]. Conclusion: The PINBALL Pilot recruitment rate was insufficient to demonstrate feasibility of a multicentre RCT of prophylactic IABC in high risk patients undergoing CABG surgery

Targeting oncogenic Src homology 2 domain-containing phosphatase 2 (SHP2) by inhibiting its protein-protein interactions

We developed a new class of inhibitors of protein-protein interactions of the SHP2 phosphatase, which is pivotal in cell signaling and represents a central target in the therapy of cancer and rare diseases. Currently available SHP2 inhibitors target the catalytic site or an allosteric pocket but lack specificity or are ineffective for disease-associated SHP2 mutants. Considering that pathogenic lesions cause signaling hyperactivation due to increased levels of SHP2 association with cognate proteins, we developed peptide-based molecules with nanomolar affinity for the N-terminal Src homology domain of SHP2, good selectivity, stability to degradation, and an affinity for pathogenic variants of SHP2 that is 2-20 times higher than for the wild-type protein. The best peptide reverted the effects of a pathogenic variant (D61G) in zebrafish embryos. Our results provide a novel route for SHP2-targeted therapies and a tool for investigating the role of protein-protein interactions in the function of SHP2

The CORDEX Flagship Pilot Study in southeastern South America: a comparative study of statistical and dynamical downscaling models in simulating daily extreme precipitation events

The aim of this work is to present preliminary results of the statistical and dynamical simulations carried out within the framework of the Flagship Pilot Study in southeastern South America (FPS-SESA) endorsed by the Coordinated Regional Climate Downscaling Experiments (CORDEX) program. The FPS-SESA initiative seeks to promote inter-institutional collaboration and further networking with focus on extreme rainfall events. The main scientific aim is to study multi-scale processes and interactions most conducive to extreme precipitation events through both statistical and dynamical downscaling techniques, including convection-permitting simulations. To this end, a targeted experiment was designed considering the season October 2009 to March 2010, a period with a record number of extreme precipitation events within SESA. Also, three individual extreme events within that season were chosen as case studies for analyzing specific regional processes and sensitivity to resolutions. Four dynamical and four statistical downscaling models (RCM and ESD respectively) from different institutions contributed to the experiment. In this work, an analysis of the capability of the set of the FPS-SESA downscaling methods in simulating daily precipitation during the selected warm season is presented together with an integrated assessment of multiple sources of observations and available CORDEX Regional Climate Model simulations. Comparisons among all simulations reveal that there is no single model that performs best in all aspects evaluated. The ability in reproducing the different features of daily precipitation depends on the model. However, the evaluation of the sequence of precipitation events, their intensity and timing suggests that FPS-SESA simulations based on both RCM and ESD yield promising results. Most models capture the extreme events selected, although with a considerable spread in accumulated values and the location of heavy precipitation.Thanks to CORDEX for endorsing the FPS-SESA. This work was supported by the University of Buenos Aires 2018- 20020170100117BA grant; JMG, MLB, SAS, RPR funding from the Spanish Research Council (CSIC) I-COOP+ Program “reference COOPB20374”. JMG, JF and AL-G acknowledge support from the Spanish R&D Program through projects MULTI-SDM (CGL2015-66583-R) and INSIGNIA (CGL2016-79210-R), co-funded by the European Regional Development Fund (ERDF/FEDER). AL-G acknowledges support from the Spanish R&D Program through the predoctoral contract BES-2016-078158. Universidad de Cantabria simulations have been carried out on the Altamira Supercomputer at the Instituto de Física de Cantabria (IFCA-CSIC), member of the Spanish Supercomputing Network. MB acknowledges support from the Simons Associateship of the Abdus Salam International Centre for Theoretical Physics. RH acknowledges support from the project LTT17007 funded by the Ministry of Education, Youth, and Sports of the Czech Republic

Wildlife collisions with aircraft: A missing component of land-use planning for airports

Projecting risks posed to aviation safety by wildlife populations is often overlooked in airport land-use planning. However, the growing dependency on civil aviation for global commerce can require increases in capacity at airports which affect land use, wildlife populations, and perspectives on aviation safety. Our objectives were to (1) review legislation that affects airports and surrounding communities relative to managing and reducing wildlife hazards to aviation; (2) identify information gaps and future research needs relative to regulated land uses on and near airports, and the effects on wildlife populations; and (3) demonstrate how information regarding wildlife responses to land-use practices can be incorporated into wildlife-strike risk assessments.We show that guidelines for land-use practices on and near airports with regard to wildlife hazards to aviation can be vague, conflicting, and scientifically ill-supported. We discuss research needs with regard to management of storm water runoff; wildlife use of agricultural crops and tillage regimens relative to revenue and safety; the role of an airport in the landscape matrix with regard to its effects on wildlife species richness and abundance; and spatial and temporal requirements of wildlife species that use airports, relative to implementing current and novel management techniques. We also encourage the development and maintenance of data sets that will allow realistic assessment of wildlife-strike risk relative to current airport conditions and anticipated changes to capacity. Land uses at airports influence wildlife populations, and understanding and incorporating these effects into planning will reduce risks posed to both aviation safety and wildlife species

The sixth international RASopathies symposium: Precision medicine—From promise to practice

The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS‐mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life‐limiting medical complications. RASopathies may benefit from precision medicine approaches. For this reason, the Sixth International RASopathies Symposium focused on exploring precision medicine. This meeting brought together basic science researchers, clinicians, clinician scientists, patient advocates, and representatives from pharmaceutical companies and the National Institutes of Health. Novel RASopathy genes, variants, and animal models were discussed in the context of medication trials and drug development. Attempts to define and measure meaningful endpoints for treatment trials were discussed, as was drug availability to patients after trial completion