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

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

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

Propranolol in the treatment of infantile haemangiomas:lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey

Oral propranolol is widely prescribed as first line treatment for infantile haemangiomas (IHs) and anecdotally prescribing practice differs widely between centres

Cancer stem cell drugs target K-ras signaling in a stemness context

Cancer stem cells (CSCs) are considered to be responsible for treatment relapse and have therefore become a major target in cancer research. Salinomycin is the most established CSC inhibitor. However, its primary mechanistic target is still unclear, impeding the discovery of compounds with similar anti-CSC activity. Here, we show that salinomycin very specifically interferes with the activity of K-ras4B, but not H-ras, by disrupting its nanoscale membrane organization. We found that caveolae negatively regulate the sensitivity to this drug. On the basis of this novel mechanistic insight, we defined a K-ras-associated and stem cell-derived gene expression signature that predicts the drug response of cancer cells to salinomycin. Consistent with therapy resistance of CSC, 8% of tumor samples in the TCGA-database displayed our signature and were associated with a significantly higher mortality. Using our K-ras-specific screening platform, we identified several new candidate CSC drugs. Two of these, ophiobolin A and conglobatin A, possessed a similar or higher potency than salinomycin. Finally, we established that the most potent compound, ophiobolin A, exerts its K-ras4B-specific activity through inactivation of calmodulin. Our data suggest that specific interference with the K-ras4B/calmodulin interaction selectively inhibits CSC.Peer reviewe

Forest fires in a changing climate and their impacts on air quality

In a future climate scenario forest fire activity over Portugal will substantially increase and consequently area burned and forest fire emissions to the atmosphere are also expected to increase. This study investigated the impact of future forest fire emissions on air quality over Portugal under the IPCC SRES A2 scenario. Reference and future climate change scenarios were simulated using the MM5/CHIMERE air quality modelling system, which was applied over Europe and over Portugal, using nesting capabilities. The initial and boundary conditions were provided by the HadAM3P model simulations for the reference and the future climate. The forest fire emissions were estimated using a methodology, which included the selection of emission factors for each pollutant, burning efficiency, fuel loads and the predicted area burned. These emissions were added to the simulation grid using specific parameterizations for their vertical distribution. Modelling results for Portugal pointed out that future forest fire activity will increase the O(3) concentrations of almost 23 mu g m(-3) by 2100 but a decrease of approximately 6 mu g m(-3) is detected close to the main forest fire locations. Future forest fire emissions will also impact the PM10 concentrations over Portugal with increases reaching 20 mu g m(-3) along the Northern coastal region in July. The highest increases are estimated over the north and centre of Portugal where the area burned projections in future climate are higher. (C) 2011 Elsevier Ltd. All rights reserved