Suchergebnisse

In response to the COVID-19 pandemic, governments declared severe restrictions throughout 2020, presenting an unprecedented scenario of reduced anthropogenic emissions of air pollutants derived mainly from traffic sources. To analyze the effect of these restrictions derived from COVID-19 pandemic on air quality levels, relative changes in NO, NO2, O3, PM10 and PM2.5 concentrations were calculated at urban traffic sites in the most populated Spanish cities over different periods with distinct restrictions in 2020. In addition to the changes calculated with respect to the observed air pollutant levels of previous years (2013-2019), relative changes were also calculated using predicted pollutant levels for the different periods over 2020 on a business-as-usual scenario using Multiple Linear Regression (MLR) models with meteorological and seasonal predictors. MLR models were selected among different data mining techniques (MLR, Random Forest (RF), K-Nearest Neighbors (KNN)), based on their higher performance and accuracy obtained from a leave-one-year-out cross-validation scheme using 2013-2019 data. A q-q mapping post-correction was also applied in all cases in order to improve the reliability of the predictions to reproduce the observed distributions and extreme events. This approach allows us to estimate the relative changes in the studied air pollutants only due to COVID-19 restrictions. The results obtained from this approach show a decreasing pattern for NOx, with the largest reduction in the lockdown period above -50%, whereas the increase observed for O3 contrasts with the NOx patterns with a maximum increase of 23.9%. The slight reduction in PM10 (-4.1%) and PM2.5 levels (-2.3%) during lockdown indicates a lower relationship with traffic sources. The developed methodology represents a simple but robust framework for exploratory analysis and intervention detection in air quality studies. ; This research was developed in the framework of the Project "Contaminación atmosférica y COVID-19: ¿Qué podemos aprender de esta pandemia?", selected in the Extraordinary BBVA Foundation grant call for SARS-CoV-2 and COVID-19 research proposals, within the area of ecology and veterinary science.

The global COVID-19 pandemic that began in late December 2019 led to unprecedented lockdowns worldwide, providing a unique opportunity to investigate in detail the impacts of restricted anthropogenic emissions on air quality. A wide range of strategies and approaches exist to achieve this. In this paper, we use the "deweather" R package, based on Boosted Regression Tree (BRT) models, first to remove the influences of meteorology and emission trend patterns from NO, NO2, PM10 and O3 data series, and then to calculate the relative changes in air pollutant levels in 2020 with respect to the previous seven years (2013-2019). Data from a northern Spanish region, Cantabria, with all types of monitoring stations (traffic, urban background, industrial and rural) were used, dividing the calendar year into eight periods according to the intensity of government restrictions. The results showed mean reductions in the lockdown period above -50% for NOx, around -10% for PM10 and below -5% for O3. Small differences were found between the relative changes obtained from normalised data with respect to those from observations. These results highlight the importance of developing an integrated policy to reduce anthropogenic emissions and the need to move towards sustainable mobility to ensure safer air quality levels, as pre-existing concentrations in some cases exceed the safe threshold.

We aimed to study the association between occupational exposure to pesticides and chronic lymphocytic leukemia (CLL) in Spain. Occupational exposure to pesticides (four insecticides, four herbicides and two fungicides) was evaluated using a job-exposure matrix for the Spanish population (MatEmESp) among 302 CLL cases and 1567 population controls in five regions of Spain, 2010?2013. Cumulative exposure scores (CES) were obtained by summing across the exposed jobs the product of prevalence, intensity and duration of exposure to each active substance. Principal components analysis (PCA) and logistic regression models adjusted for age, sex, region, education and occupational exposure to solvents were used. Around 20% of controls and 29% of cases were exposed to one or more pesticides. Compared to non-exposed, subjects in the highest tertile (3rd tertile) of CES of insecticides, herbicides, fungicides were more likely to have CLL [OR (95% CI), P-trend; 2.10 (1.38; 3.19), 0.002; 1.77 (1.12; 2.80), 0.12; and 1.67 (1.06; 2.64), 0.10, respectively). Following PCA, the first component (PC1, explaining 70% of the variation) equally led by seven active substances (the insecticide pyrethrin, all herbicides, all fungicides) was associated with a 26% higher odds of having CLL for 1-standard deviation increase in PC1 (95% CI: 1.14 to 1.40). These results confirm previous associations between CLL and exposure to pesticides and provide additional evidence by application groups and active substance. However, more research is needed to disentangle independent e ects of individual active substances. ; We thank CERCA programme/Generalitat de Catalunya for institutional support. This work was supported by Spanish Ministry of Economy and Competitiveness—Carlos III Institute of Health co-funded by FEDER funds/European Regional Develpment Fund (ERDF)—A way to build Europe (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PI11/01403, PI11/02213, PI14/1219, PI15/00966, PI17/01280, RTIC RD06/0020/0095, RD12/0036/0036, SV-09-CLINIC-1 and CIBERESP), by Juan de la Cierva (IJCI-2016-29502), by the Fundación Marques de Valdecilla (API 10/09), by Obra Social CAJASTUR (SV-CAJASTUR-1), by the Recercaixa (2010ACUP 00310 and with the support of the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia (2017SGR1085). The ICGC CLL-Genome Project was funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII), PMP15/00007 and CIBERONC del ISCIII. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.

Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus can play in 55e90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole-exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, Merkel cell polyomavirus-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their Merkel cell polyomavirus-positive counterparts. Despite important genetic differences, the two Merkel cell carcinoma etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT or nuclear factor of activated T cells (NFAT), P-CREB, and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified phosphorylated CRE-binding protein as an independent survival factor with respect to clinical variables and Merkel cell polyomavirus status in our cohort of Merkel cell carcinoma patients. ; This work was supported by grants from Instituto de Salud-Carlos III (ISCIII); cofinanced by the European Union; (FEDER) (PI12/00357), and a Ramón and Cajal research program (MINECO; RYC-2013-14097) to JPV, Asociación Española Contra el Cáncer and ISCIII grants (RD06/0020/0107, RD012/0036/0060) to MAP, and Coordinated Project of Excellence inter-Institutos de investigación acreditados institutes (ISCIII; PIE15/00081) to MAP. The Ramón and Cajal research program also supports IV. SD was supported by the Torres Quevedo subprogram (MICINN; PTQ-12-05391).

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There is increasing interest in developing specific markers to serve as predictors of response to sorafenib and to guide targeted therapy. Using a sequencing platform designed to study somatic mutations in a selection of 112 genes (HepatoExome), we aimed to characterize lesions from HCC patients and cell lines, and to use the data to study the biological and mechanistic effects of case-specific targeted therapies used alone or in combination with sorafenib. We characterized 331 HCC cases in silico and 32 paired samples obtained prospectively from primary tumors of HCC patients. Each case was analyzed in a time compatible with the requirements of the clinic (within 15 days). In 53% of the discovery cohort cases, we detected unique mutational signatures, with up to 34% of them carrying mutated genes with the potential to guide therapy. In a panel of HCC cell lines, each characterized by a specific mutational signature, sorafenib elicited heterogeneous mechanistic and biological responses, whereas targeted therapy provoked the robust inhibition of cell proliferation and DNA synthesis along with the blockage of AKT/mTOR signaling. The combination of sorafenib with targeted therapies exhibited synergistic anti-HCC biological activity concomitantly with highly effective inhibition of MAPK and AKT/mTOR signaling. Thus, somatic mutations may lead to identify case-specific mechanisms of disease in HCC lesions arising from multiple etiologies. Moreover, targeted therapies guided by molecular characterization, used alone or in combination with sorafenib, can effectively block important HCC disease mechanisms. ; FUNDING: Grants from ISCIII, co-financed by the European Union (FEDER) (PI16/00156), Ramón and Cajal research program from MINECO (RYC-2013-14097) and FUNDACIÓN LUCHAMOS POR LA VIDA to JPV. Grants from ISCIII (RD06/0020/0107-RD012/0036/0060) to MAP. Grant from ISCIII (Ref. PIE15/00079) to JC & JPV. NGD is a recipient of a UC-IDIVAL pre-doctoral fellow. I.V. was also supported by the Ramón and Cajal research program.