Anthracological evidence suggests naturalness of Pinus pinaster in inland southwestern Iberia

The study of well-preserved archaeological charcoals in the pre-Roman Iron Age settlement of Castillejos II (Badajoz, Spain) is used to reconstruct environmental conditions and land-use practices in vegetation landscapes in the southwest of the Iberian Peninsula before the arrival of Roman civilization. The results support that, while evergreen Quercus forests dominated during the Holocene, Pinus pinaster existed as a natural element of southwestern Iberian Peninsula vegetation. Although its presence could be linked to anthropogenic disturbance or fire history, it is suggested that P. pinaster populations survived during the Holocene in the region, mixed with oaks or in monospecific stands in mountain enclaves. This hypothesis contrasts with previous assumptions that P. pinaster was not autochthonous in the area

Baseline JAK phosphorylation profile of peripheral blood leukocytes, studied by whole blood phosphospecific flow cytometry, is associated with 1-year treatment response in early rheumatoid arthritis

Background: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4(+) T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA. Methods: Thirty-five DMARD-naive patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes. Treatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as absence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used to investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were estimated by bias-corrected bootstrapping. Results: High JAK3 phosphorylation in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes and low JAK2 phosphorylation in CD14(+) monocytes were significantly associated with remission following treatment with synthetic DMARDs. Conclusions: Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA.Peer reviewe

Demonstration of the event identification capabilities of the NEXT-White detector

In experiments searching for neutrinoless double-beta decay, the possibility of identifying the two emitted electrons is a powerful tool in rejecting background events and therefore improving the overall sensitivity of the experiment. In this paper we present the first measurement of the efficiency of a cut based on the different event signatures of double and single electron tracks, using the data of the NEXT-White detector, the first detector of the NEXT experiment operating underground. Using a 228Th calibration source to produce signal-like and background-like events with energies near 1.6 MeV, a signal efficiency of 71.6 ± 1.5 stat± 0.3 sys% for a background acceptance of 20.6 ± 0.4 stat± 0.3 sys% is found, in good agreement with Monte Carlo simulations. An extrapolation to the energy region of the neutrinoless double beta decay by means of Monte Carlo simulations is also carried out, and the results obtained show an improvement in background rejection over those obtained at lower energies. [Figure not available: see fulltext.

Radiogenic backgrounds in the NEXT double beta decay experiment

Natural radioactivity represents one of the main backgrounds in the search for neutrinoless double beta decay. Within the NEXT physics program, the radioactivity- induced backgrounds are measured with the NEXT-White detector. Data from 37.9 days of low-background operations at the Laboratorio Subterráneo de Canfranc with xenon depleted in 136Xe are analyzed to derive a total background rate of (0.84±0.02) mHz above 1000 keV. The comparison of data samples with and without the use of the radon abatement system demonstrates that the contribution of airborne-Rn is negligible. A radiogenic background model is built upon the extensive radiopurity screening campaign conducted by the NEXT collaboration. A spectral fit to this model yields the specific contributions of 60Co, 40K, 214Bi and 208Tl to the total background rate, as well as their location in the detector volumes. The results are used to evaluate the impact of the radiogenic backgrounds in the double beta decay analyses, after the application of topological cuts that reduce the total rate to (0.25±0.01) mHz. Based on the best-fit background model, the NEXT-White median sensitivity to the two-neutrino double beta decay is found to be 3.5σ after 1 year of data taking. The background measurement in a Qββ±100 keV energy window validates the best-fit background model also for the neutrinoless double beta decay search with NEXT-100. Only one event is found, while the model expectation is (0.75±0.12) events. [Figure not available: see fulltext.]

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia

Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. Patients and methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94–1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97–1.22). Discussion and conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself

The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi

Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1−/− mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1−/− mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-γ production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-γ in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background: Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. / Methods: We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. / Findings: Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). / Interpretation: These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. / Funding: The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Diversity of isoprene-degrading bacteria in phyllosphere and soil communities from a high isoprene-emitting environment: a Malaysian oil palm plantation

Background: Isoprene is the most abundantly produced biogenic volatile organic compound (BVOC) on Earth, with annual global emissions almost equal to those of methane. Despite its importance in atmospheric chemistry and climate, little is known about the biological degradation of isoprene in the environment. The largest source of isoprene is terrestrial plants, and oil palms, the cultivation of which is expanding rapidly, are among the highest isoprene-producing trees. Results: DNA stable isotope probing (DNA-SIP) to study the microbial isoprene-degrading community associated with oil palm trees revealed novel genera of isoprene-utilising bacteria including Novosphingobium, Pelomonas, Rhodoblastus, Sphingomonas and Zoogloea in both oil palm soils and on leaves. Amplicon sequencing of isoA genes, which encode the α-subunit of the isoprene monooxygenase (IsoMO), a key enzyme in isoprene metabolism, confirmed that oil palm trees harbour a novel diversity of isoA sequences. In addition, metagenome assembled genomes (MAGs) were reconstructed from oil palm soil and leaf metagenomes and putative isoprene degradation genes were identified. Analysis of unenriched metagenomes showed that isoA-containing bacteria are more abundant in soils than in the oil palm phyllosphere. Conclusion: This study greatly expands the known diversity of bacteria that can metabolise isoprene and contributes to a better understanding of the biological degradation of this important but neglected climate-active gas

Electroluminescence TPCs at the thermal diffusion limit

[EN] The NEXT experiment aims at searching for the hypothetical neutrinoless double-beta decay from the 136Xe isotope using a high-purity xenon TPC. Efficient discrimination of the events through pattern recognition of the topology of primary ionisation tracks is a major requirement for the experiment. However, it is limited by the diffusion of electrons. It is known that the addition of a small fraction of a molecular gas to xenon reduces electron diffusion. On the other hand, the electroluminescence (EL) yield drops and the achievable energy resolution may be compromised. We have studied the effect of adding several molecular gases to xenon (CO2, CH4 and CF4) on the EL yield and energy resolution obtained in a small prototype of driftless gas proportional scintillation counter. We have compared our results on the scintillation characteristics (EL yield and energy resolution) with a microscopic simulation, obtaining the diffusion coefficients in those conditions as well. Accordingly, electron diffusion may be reduced from about 10 mm/ sqrt(¿) for pure xenon down to 2.5 mm/sqrt(m) using additive concentrations of about 0.05%, 0.2% and 0.02% for CO2, CH4 and CF4, respectively. Our results show that CF4 admixtures present the highest EL yield in those conditions, but very poor energy resolution as a result of huge fluctuations observed in the EL formation. CH4 presents the best energy resolution despite the EL yield being the lowest. The results obtained with xenon admixtures are extrapolated to the operational conditions of the NEXT-100 TPC. CO2 and CH4 show potential as molecular additives in a large xenon TPC. While CO2 has some operational constraints, making it difficult to be used in a large TPC, CH4 shows the best performance and stability as molecular additive to be used in the NEXT-100 TPC, with an extrapolated energy resolution of 0.4% at 2.45 MeV for concentrations below 0.4%, which is only slightly worse than the one obtained for pure xenon. We demonstrate the possibility to have an electroluminescence TPC operating very close to the thermal diffusion limit without jeopardizing the TPC performance, if CO2 or CH4 are chosen as additives.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Marie Sklodowska-Curie Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economia y Competitividad of Spain under grants FIS2014-53371-C04, the Severo Ochoa Program SEV-2014-0398 and the Maria de Maetzu Program MDM-2016-0692; the GVA of Spain under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014, under project UID/FIS/04559/2013 to fund the activities of LIBPhys, and under grants PD/BD/105921/2014, SFRH/BPD/109180/2015 and SFRH/BPD/76842/2011; the U.S. Department of Energy under contracts number DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-AC02-06CH11357 (Argonne National Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0017721 (University of Texas at Arlington); and the University of Texas at Arlington. DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC-2015-18820. We also warmly acknowledge the Laboratori Nazionali del Gran Sasso (LNGS) and the Dark Side collaboration for their help with TPB coating of various parts of the NEXT-White TPC. Finally, we are grateful to the Laboratorio Subterraneo de Canfranc for hosting and supporting the NEXT experiment.Henriques, CAO.; Monteiro, CMB.; Gonzalez-Diaz, D.; Azevedo, CDR.; Freitas, EDC.; Mano, RDP.; Jorge, MR.... (2019). Electroluminescence TPCs at the thermal diffusion limit. Journal of High Energy Physics (Online). 1:1-20. https://doi.org/10.1007/JHEP01(2019)027S1201NEXT collaboration, J. Martín-Albo et al., Sensitivity of NEXT-100 to neutrinoless double beta decay, JHEP 05 (2016) 159 [ arXiv:1511.09246 ] [ INSPIRE ].T. Brunner et al., An RF-only ion-funnel for extraction from high-pressure gases, Intern. J. Mass Spectrom. 379 (2015) 110 [ INSPIRE ].PANDAX-III collaboration, J. Galan, Microbulk MicrOMEGAs for the search of 0νββ of 136 Xe in the PandaX-III experiment, 2016 JINST 11 P04024 [ arXiv:1512.09034 ] [ INSPIRE ].D. Yu. Akimov, A.A. Burenkov, V.F. Kuzichev, V.L. Morgunov and V.N. Solovev, Low background experiments with high pressure gas scintillation proportional detector, physics/9704021 [ INSPIRE ].Yu. M. Gavrilyuk et al., A technique for searching for the 2K capture in 124 Xe with a copper proportional counter, Phys. Atom. Nucl. 78 (2015) 1563 [ INSPIRE ].D.R. Nygren, Columnar recombination: a tool for nuclear recoil directional sensitivity in a xenon-based direct detection WIMP search, J. Phys. Conf. Ser. 460 (2013) 012006 [ INSPIRE ].XENON collaboration, E. Aprile et al., First Dark Matter Search Results from the XENON1T Experiment, Phys. Rev. Lett. 119 (2017) 181301 [ arXiv:1705.06655 ] [ INSPIRE ].XENON100 collaboration, E. Aprile et al., Dark Matter Results from 225 Live Days of XENON100 Data, Phys. Rev. Lett. 109 (2012) 181301 [ arXiv:1207.5988 ] [ INSPIRE ].LUX collaboration, D.S. Akerib et al., Results from a search for dark matter in the complete LUX exposure, Phys. Rev. Lett. 118 (2017) 021303 [ arXiv:1608.07648 ] [ INSPIRE ].PandaX-II collaboration, X. Cui et al., Dark Matter Results From 54-Ton-Day Exposure of PandaX-II Experiment, Phys. Rev. Lett. 119 (2017) 181302 [ arXiv:1708.06917 ] [ INSPIRE ].EXO collaboration, J.B. Albert et al., Search for Neutrinoless Double-Beta Decay with the Upgraded EXO-200 Detector, Phys. Rev. Lett. 120 (2018) 072701 [ arXiv:1707.08707 ] [ INSPIRE ].KamLAND-Zen collaboration, A. Gando et al., Search for Majorana Neutrinos near the Inverted Mass Hierarchy Region with KamLAND-Zen, Phys. Rev. Lett. 117 (2016) 082503 [ arXiv:1605.02889 ] [ INSPIRE ].XMASS collaboration, K. Abe et al., Search for two-neutrino double electron capture on 124 Xe with the XMASS-I detector, Phys. Lett. B 759 (2016) 64 [ arXiv:1510.00754 ] [ INSPIRE ].XENON collaboration, E. Aprile et al., Search for two-neutrino double electron capture of 124 Xe with XENON100, Phys. Rev. C 95 (2017) 024605 [ arXiv:1609.03354 ] [ INSPIRE ].R. Lüscher et al., Search for ββ decay in 136 Xe: new results from the Gotthard experiment, Phys. Lett. B 434 (1998) 407 [ INSPIRE ].NEXT collaboration, P. Ferrario et al., First proof of topological signature in the high pressure xenon gas TPC with electroluminescence amplification for the NEXT experiment, JHEP 01 (2016) 104 [ arXiv:1507.05902 ] [ INSPIRE ].NEXT collaboration, D. Lorca et al., Characterisation of NEXT-DEMO using xenon K α X-rays, 2014 JINST 9 P10007 [ arXiv:1407.3966 ] [ INSPIRE ].NEXT collaboration, D. González-Díaz et al., Accurate γ and MeV-electron track reconstruction with an ultra-low diffusion Xenon/TMA TPC at 10 atm, Nucl. Instrum. Meth. A 804 (2015) 8 [ arXiv:1504.03678 ] [ INSPIRE ].C.M.B. Monteiro et al., Secondary Scintillation Yield in Pure Xenon, 2007 JINST 2 P05001 [ physics/0702142 ] [ INSPIRE ].C.M.B. Monteiro, J.A.M. Lopes, J.F. C.A. Veloso and J.M.F. dos Santos, Secondary scintillation yield in pure argon, Phys. Lett. B 668 (2008) 167 [ INSPIRE ].E.D.C. Freitas et al., Secondary scintillation yield in high-pressure xenon gas for neutrinoless double beta decay (0νββ) search, Phys. Lett. B 684 (2010) 205 [ INSPIRE ].C.M.B. Monteiro et al., Secondary scintillation yield from gaseous micropattern electron multipliers in direct dark matter detection, Phys. Lett. B 677 (2009) 133 [ INSPIRE ].C.M.B. Monteiro, L.M.P. Fernandes, J.F. C.A. Veloso, C.A.B. Oliveira and J.M.F. dos Santos, Secondary scintillation yield from GEM and THGEM gaseous electron multipliers for direct dark matter search, Phys. Lett. B 714 (2012) 18 [ INSPIRE ].C. Balan et al., MicrOMEGAs operation in high pressure xenon: Charge and scintillation readout, 2011 JINST 6 P02006 [ arXiv:1009.2960 ] [ INSPIRE ].J.M.F. dos Santos et al., Development of portable gas proportional scintillation counters for x-ray spectrometry, X-Ray Spectrom. 30 (2001) 373.NEXT collaboration, J. Renner et al., Background rejection in NEXT using deep neural networks, 2017 JINST 12 T01004 [ arXiv:1609.06202 ] [ INSPIRE ].T. Himi et al., Emission spectra from Ar-Xe, Ar-Kr, Ar-N2, Ar-CH4, Ar-CO2 and Xe-N2 gas proportional scintillation counters, Nucl. Instrum. Meth. 205 (1983) 591.C.D.R. Azevedo et al., An homeopathic cure to pure Xenon large diffusion, 2016 JINST 11 C02007 [ arXiv:1511.07189 ] [ INSPIRE ].NEXT collaboration, C.A.O. Henriques et al., Secondary scintillation yield of xenon with sub-percent levels of CO 2 additive for rare-event detection, Phys. Lett. B 773 (2017) 663 [ arXiv:1704.01623 ] [ INSPIRE ].P.C.P.S. Simões, J.M.F. dos Santos and C.A.N. Conde, Driftless gas proportional scintillation counter pulse analysis using digital processing techniques, X Ray Spectrom. 30 (2001) 342.P.C.P.S. Simões et al., A new method for pulse analysis of driftless-gas proportional scintillation counters, Nucl. Instrum. Meth. A 505 (2003) 247.C.D.R. Azevedo et al., Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives, Nucl. Instrum. Meth. A 877 (2018) 157 [ arXiv:1705.09481 ] [ INSPIRE ].L.M.P. Fernandes et al., Primary and secondary scintillation measurements in a xenon Gas Proportional Scintillation Counter, 2010 JINST 5 P09006 [Erratum ibid. 5 (2010) A12001] [ arXiv:1009.2719 ] [ INSPIRE ].C.M.B. Monteiro et al., An argon gas proportional scintillation counter with UV avalanche photodiode scintillation readout, IEEE Trans. Nucl. Sci. 48 (2001) 1081.J.A.M. Lopes et al., A xenon gas proportional scintillation counter with a UV-sensitive large-area avalanche photodiode, IEEE Trans. Nucl. Sci. 48 (2001) 312.D.F. Anderson et al., A large area gas scintillation proportional counter, Nucl. Instrum. Meth. 163 (1979) 125.Z. Kowalski et al., Fano factor implications from gas scintillation proportional counter measurements, Nucl. Instrum. Meth. A 279 (1989) 567.S.J.C. do Carmo et al., Experimental study of the ω-values and Fano factors of gaseous xenon and Ar-Xe mixtures for X-rays, IEEE Trans. Nucl. Sci. 55 (2008) 2637.http://magboltz.web.cern.ch/magboltz/ (accessed 14.11.2016).T.H.V.T. Dias et al., Full-energy absorption of x-ray energies near the Xe L- and K-photoionization thresholds in xenon gas detectors: Simulation and experimental results, J. Appl. Phys. 82 (1997) 2742.D. Nygren, High-pressure xenon gas electroluminescent TPC for 0νββ-decay search, Nucl. Instrum. Meth. A 603 (2009) 337 [ INSPIRE ].NEXT collaboration, V. Álvarez et al., The NEXT-100 experiment for neutrinoless double beta decay searches (Conceptual Design Report), arXiv:1106.3630 [ INSPIRE ].NEXT collaboration, V. Álvarez et al., Operation and first results of the NEXT-DEMO prototype using a silicon photomultiplier tracking array, 2013 JINST 8 P09011 [ arXiv:1306.0471 ] [ INSPIRE ]