Lead and other toxic metals in playground paints from South West England

Paints on surfaces of public playground structures in south west England have been analysed for Pb, Cr, Cd and Sb by field-portable, energy-dispersive XRF. Lead was detected (> 8 g g-1) in 102 out of 242 cases, with concentrations ranging from 10 to 152,000 g g-1 (median = 451 g g-1). Chromium was detected (> 25 g g-1) in 48 cases, and concentrations ranged from 26 to 24,800 g g-1 (median = 1,040 g g-1) and exhibited a significant positive correlation with Pb concentrations. Antimony concentrations ranged from 273 to 16,000 g g-1 (median = 2,180 g g-1) in 56 detectable cases, and Cd was detected in eight paints and up to a concentration of 771 g g-1 (median = 252 g g-1). The highest concentrations of Pb, Cr and Sb generally occurred in yellow or red paints but were encountered on a variety of structures and equipment (e.g. gates, flooring lines, railings and handles of climbing frames and seesaws, and the interior of a model train) and were observed in both flaking, extant paint and in formulations that appeared to have been recently applied. Maximum bioaccessible concentrations of Pb, Cr and Sb in a range of paints, evaluated in selected samples by ICP analysis following pepsin-dilute HCl extraction, were 2,710, 205 and 23.6 g g-1, respectively, or 16.6, 2.25 and 0.56% of the respective total concentrations. Total and bioaccessible concentrations of toxic metals in playground paints that exceed various contemporary and historical standards (and in many cases for Pb, by orders of magnitude) is likely to be a more widespread and pervasive issue that needs addressing by the relevant authorities

Climate-driven changes in air quality over Europe by the end of the 21st century, with special reference to Portugal

Climate change alone may deeply impact air quality levels in the atmosphere because the changes in the meteorological conditions will induce changes on the transport, dispersion and transformation of air pollutants. The aim of this work was to evaluate the impact of climate change on the air quality over Europe and Portugal, using a reference year (year 1990) and a IPCC SRES A2 year (year 2100). The Hadley Centre global atmospheric circulation model (HadAM3P) was used to provide results for these two climatic scenarios, which were then used as synoptic forcing for the MM5-CHIMERE air quality modelling system. In order to assess the contribution of future climate change on 03 and PM concentrations, no changes in regional emissions were assumed and only climate change forcing was considered. The modelling results suggest that the O(3) monthly mean levels in the atmosphere may increase almost 50 mu g m(-3) across Europe in July under the IPCC SRES A2 scenario. In Portugal, this increase may reach 20 mu g m(-3). The changes of PM10 monthly average values over Europe will depend on the region. The increase in PM10 concentrations during specific months could be explained by the average reduction of the boundary layer height and wind speed. (C) 2010 Elsevier Ltd. All rights reserved

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

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

Observed and Projected Hydroclimate Changes in the Andes

The Andes is the most biodiverse region across the globe. In addition, some of the largest urban areas in South America are located within this region. Therefore, ecosystems and human population are affected by hydroclimate changes reported at global, regional and local scales. This paper summarizes progress of knowledge about long-term trends observed during the last two millennia over the entire Andes, with more detail for the period since the second half of the 20th century, and presents a synthesis of climate change projections by the end of the 21st century. In particular, this paper focuses on temperature, precipitation and surface runoff in the Andes. Changes in the Andean cryosphere are not included here since this particular topic is discussed in other paper in this Frontiers special issue, and elsewhere (e.g. IPCC,2019b). While previous works have reviewed the hydroclimate of South America and particular sectors (i.e., Amazon and La Plata basins, the Altiplano, Northern South America, etc.) this review includes for the first time the entire Andes region, considering all latitudinal ranges: tropical (North of 27°S), subtropical (27°S−37°S) and extratropical (South of 37°S). This paper provides a comprehensive view of past and recent changes, as well as available climate change projections, over the entire Andean range. From this review, the main knowledge gaps are highlighted and urgent research necessities in order to provide more mechanistic understanding of hydroclimate changes in the Andes and more confident projections of its possible changes in association with global climate change.Fil: Pabón Caicedo, José Daniel. Universidad Nacional de Colombia; ColombiaFil: Arias, Paola A.. Universidad de Antioquia; ColombiaFil: Carril, Andrea Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Espinoza, Jhan Carlo. Universite Grenoble Alpes; FranciaFil: Fita Borrell, Lluís. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Goubanova, Katerina. Centro de Estudios Avanzados en Zonas Áridas; ChileFil: Lavado Casimiro, Waldo. No especifíca;Fil: Masiokas, Mariano Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Solman, Silvina Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Villalba, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

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 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