Identifying structures in the continuum: Application to 16 Be

Background: The population and decay of two-nucleon resonances offer exciting new opportunities to explore dripline phenomena. A proper understanding of these systems requires a solid description of the three-body (core+N +N) continuum. The identification of a state with resonant character from the background of nonresonant continuum states in the same energy range poses a theoretical challenge. Purpose: Establish a robust theoretical framework to identify and characterize three-body resonances in a discrete basis, and apply the method to the two-neutron unbound system 16Be. Method: A resonance operator is proposed, which describes the sensitivity to changes in the potential. Resonances,understoodasnormalizablestatesdescribinglocalizedcontinuumstructures,areidentifiedfromthe eigenstates of the resonance operator with large negative eigenvalues. For this purpose, the resonance operator is diagonalizedinabasisofHamiltonianpseudostates,whichinthepresentworkarebuiltwithinthehyperspherical harmonics formalism using the analytical transformed harmonic oscillator basis. The energy and width of the resonance are determined from its time dependence. Results: The method is applied to 16Be in a 14Be+n+n model. An effective core+n potential, fitted to the available experimental information on the binary subsystem 15Be, is employed. The 0+ ground state resonance of 16Be presents a strong dineutron configuration. This favors the picture of a correlated two-neutron emission. Fitting the three body interaction to the experimental two-neutron separation energy |S2n|=1.35(10) MeV, the computed width is (0+)=0.16 MeV. From the same Hamiltonian, a 2+ resonance is also predicted with εr(2+)=2.42 MeV and (2+)=0.40 MeV. Conclusions: The dineutron configuration and the computed 0+ width are consistent with previous R-matrix calculationsforthetruethree-bodycontinuum.Theextractedvaluesoftheresonanceenergyandwidthconverge with the size of the pseudostate basis and are robust under changes in the basis parameters. This supports the reliability of the method in describing the properties of unbound core+N +N systems in a discrete basis.Spanish Ministerio de Ciencia, Innovación y Universidades, European Regional Development Fund (FEDER), (FIS2017-88410-P, FPA2016-77689-C2-1-R, FIS2014-51941-P )European Union’s Horizon 2020 (No. 654002

Determining astrophysical three-body radiative capture reaction rates from inclusive Coulomb break-up measurements

A relationship between the Coulomb inclusive break-up probability and the radiative capture reaction rate for weakly bound three-body systems is established. This direct link provides a robust procedure to estimate the reaction rate for nuclei of astrophysical interest by measuring inclusive break-up processes at different energies and angles. This might be an advantageous alternative to the determination of reaction rates from the measurement of B(E1) distributions through exclusive Coulomb break-up experiments. In addition, it provides a reference to assess the validity of different theoretical approaches that have been used to calculate reaction rates. The procedure is applied to Li11 (Li9+n+n) and He6 (He4+n+n) three-body systems for which some data exist.This work has been partially supported by the Spanish Ministerio de Economía y Competitividad and the European Regional Development Fund (FEDER) under Projects No. FIS2011-28738-c02-01, No. FIS2013-41994-P, No. FPA2013-47327- C2-1-R, No. FIS2014-53448-c2-1-P, and FIS2014-51941-P and by Junta de Andalucía under Group No. FQM-160 and Project No. P11-FQM-7632. J. Casal acknowledges support from the Ministerio de Educacion, Cultura y Deporte, FPU Research Grant No. AP2010-3124. M. Rodríguez-Gallardo acknowledges postdoctoral support from the Universidad de Sevilla under the V Plan Propio de Investigacion, Contract No. USE-11206-M.Peer Reviewe

Water quality monitoring program through the KduSTICK, a low-cost and Do-It-Yourself instrument connected by the Internet of Things

Monitoring water transparency provides an indicator of the environmental status of the water body. One parameter to estimate the water transparency is the light difuse attenuation coefcient (Kd). In the framework of the H2020 project MONOCLE (Multiscale Observation Networks for Optical monitoring of Coastal waters, Lakes and Estuaries), we have developed an improved version of the KdUINO (Bardaji et al., 2016) consisting of a moored instrument used to assess water transparency. This new version, the KduSTICK, estimates Kd near the surface in real-time following these specifcations: cost-efective, portable, real-time monitoring and easy to use with minimal training. This instrument transmits data by using the Internet of Things (IoT) networks. In particular, our research group participates in the initiative “The Things Network” (TTN), an IoT network based on LoRaWAN. This device is easy to deploy and maintain, and it is suitable for citizen-science based water quality monitoring programs.Peer ReviewedObjectius de Desenvolupament Sostenible::6 - Aigua Neta i Sanejament::6.3 - Per a 2030, millorar la qualitat de l’aigua mitjançant la reducció de la contaminació, l’eliminació dels abocaments i la reducció al mínim de la descàrrega de materials i productes químics perillosos, la reducció a la meitat del percentatge d’aigües residuals sense tractar, i un augment substancial a escala mundial del reciclat i de la reutilització en condicions de segureta

Risk factors associated withStreptococcus suiscases on pigfarms in Spain

Background Streptococcus suis can cause meningitis, polyarthritis and acute death in piglets. However, the risk factors associated with S. suis infection remain incompletely understood. Therefore, a longitudinal study was carried out, in which six batches from two Spanish pig farms with S. suis problems were repeatedly examined to determine possible risk factors. Methods A prospective case–control study was conducted, and potential risk factors were evaluated using mixed-effects logistic regression models. The explanatory variables included: (a) concomitant pathogens; (b) biomarkers associated with stress, inflammation and oxidative status; (c) farm environmental factors; and (d) parity and S. suis presence in sows. Three models were built to study the effect of these variables, including two to assess the risk factors involved in the subsequent development of disease. Results Risk factors for S. suis-associated disease included porcine reproductive and respiratory syndrome virus co-infection at weaning (odds ratio [OR] = 6.69), sow parity (OR = 0.71), haptoglobin level before weaning (OR = 1.01), relative humidity (OR = 1.11) and temperature (OR = 0.13). Limitations Laboratory diagnosis was done at the batch level, with individual diagnosis based on clinical signs only. Conclusions This study confirms the multifactorial nature of S. suis-associated disease, with both environmental factors and factors related to the host involved in disease development. Controlling these factors may, therefore, help prevent the appearance of disease.Program for Innovative Global Prevention of Streptococcus suis (PIGSs), from program Horizon 2020 of the European Commission. Carlos Neila-Ibáñez was funded by the same project, Grant/Award Number: 727966info:eu-repo/semantics/publishedVersio

Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non-Small-Cell Lung Cancer (NADIM phase II trial)

Càncer de pulmó; Quimioteràpia neoadjuvantCáncer de pulmón; Quimioterapia neoadyuvanteLung cancer; Neoadjuvant chemotherapyPURPOSE Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non–small-cell lung cancer (NSCLC) in the NADIM trial (ClinicalTrials.gov identifier: NCT03081689). The 3-year overall survival (OS) and circulating tumor DNA (ctDNA) analysis have not been reported. METHODS This was an open-label, multicenter, single-arm, phase II trial in which patients with stage IIIA NSCLC, who were deemed to be surgically resectable, were treated with neoadjuvant paclitaxel (200 mg/m2 once a day) and carboplatin (area under curve 6) plus nivolumab (360 mg) once on day 1 of each 21-day cycle, for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The 3-year OS and ctDNA analysis were secondary objectives of the trial. RESULTS OS at 36 months was 81.9% (95% CI, 66.8 to 90.6) in the intention-to-treat population, rising to 91.0% (95% CI, 74.2 to 97.0) in the per-protocol population. Neither tumor mutation burden nor programmed cell death ligand-1 staining was predictive of survival. Conversely, low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and OS (hazard ratio [HR], 0.20; 95% CI, 0.06 to 0.63, and HR, 0.07; 95% CI, 0.01 to 0.39, respectively). Clinical responses according to RECIST v1.1 criteria did not predict survival outcomes. However, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and OS (HR, 0.26; 95% CI, 0.07 to 0.93, and HR, 0.04; 95% CI, 0.00 to 0.55, respectively). The C-index to predict OS for ctDNA levels after neoadjuvant treatment (0.82) was superior to that of RECIST criteria (0.72). CONCLUSION The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3-year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival

VE-cadherin RGD motifs promote metastasis and constitute a potential therapeutic target in melanoma and breast cancers

13 p.-6 fig.We have investigated the role of vascular-endothelial (VE)-cadherin in melanoma and breast cancer metastasis. We found that VE-cadherin is expressed in highly aggressive melanoma and breast cancer cell lines. Remarkably, inactivation of VEcadherin triggered a significant loss of malignant traits (proliferation, adhesion, invasion and transendothelial migration) in melanoma and breast cancer cells. These effects, except transendothelial migration, were induced by the VE-cadherin RGD motifs. Co-immunoprecipitation experiments demonstrated an interaction between VE-cadherin and α2β1 integrin, with the RGD motifs found to directly affect β1 integrin activation. VE-cadherin-mediated integrin signaling occurred through specific activation of SRC, ERK and JNK, including AKT in melanoma. Knocking down VEcadherin suppressed lung colonization capacity of melanoma or breast cancer cells inoculated in mice, while pre-incubation with VE-cadherin RGD peptides promoted lung metastasis for both cancer types. Finally, an in silico study revealed the association of high VE-cadherin expression with poor survival in a subset of melanoma patients and breast cancer patients showing low CD34 expression. These findings support a general role for VE-cadherin and other RGD cadherins as critical regulators of lung and liver metastasis in multiple solid tumours. These results pave the way for cadherin-specific RGD targeted therapies to control disseminated metastasis in multiple cancers.BEP was an FPI fellow from Ministry of Economy and Competitiveness (MINECO). This research was supported by grants BIO2012-31023 and BIO2015-66849 from MINECO and PRB2 (IPT13/0001-ISCIII-SGEFI/FEDER) to JIC.Peer reviewe

Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non–Small-Cell Lung Cancer (NADIM phase II trial)

PURPOSE Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non–small cell lung cancer (NSCLC) in the NADIM trial (ClinicalTrials.gov identifier: NCT03081689). The 3-year overall survival (OS) and circulating tumor DNA (ctDNA) analysis have not been reported. METHODS This was an open-label, multicenter, single-arm, phase II trial in which patients with stage IIIA NSCLC, who were deemed to be surgically resectable, were treated with neoadjuvant paclitaxel (200 mg/m2 once a day) and carboplatin (area under curve 6) plus nivolumab (360 mg) once on day 1 of each 21-day cycle, for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The 3-year OS and ctDNA analysis were secondary objectives of the trial. RESULTS OS at 36 months was 81.9% (95% CI, 66.8 to 90.6) in the intention-to-treat population, rising to 91.0% (95% CI, 74.2 to 97.0) in the per-protocol population. Neither tumor mutation burden nor programmed cell death ligand-1 staining was predictive of survival. Conversely, low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and OS (hazard ratio [HR], 0.20; 95% CI, 0.06 to 0.63, and HR, 0.07; 95% CI, 0.01 to 0.39, respectively). Clinical responses according to RECIST v1.1 criteria did not predict survival outcomes. However, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and OS (HR, 0.26; 95% CI, 0.07 to 0.93, and HR, 0.04; 95% CI, 0.00 to 0.55, respectively). The C-index to predict OS for ctDNA levels after neoadjuvant treatment (0.82) was superior to that of RECIST criteria (0.72). CONCLUSION The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3- year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival

Perimeter and carvacrol-loading regulate angiogenesis and biofilm growth in 3D printed PLA scaffolds

rvacrol is a natural low-cost compound derived from oregano which presents anti-bacterial properties against both Gram-positive and Gram-negative bacteria. In this work, carvacrol-loaded PLA scaffolds were fabricated by 3D printing as platforms to support bone tissue regeneration while preventing biofilm development. Scaffolds were printed with or without a perimeter (lateral wall) mimicking the cortical structure of bone tissue to further evaluate if the lateral interconnectivity could affect the biological or antimicrobial properties of the scaffolds. Carvacrol incorporation was performed by loading either the PLA filament prior to 3D printing or the already printed PLA scaffold. The loading method determined carvacrol localization in the scaffolds and its release profile. Biphasic profiles were recorded in all cases, but scaffolds loaded post-printed released carvacrol much faster, with 50–80% released in the first day, compared to those containing carvacrol in PLA filament before printing which sustained the release for several weeks. The presence or absence of the perimeter did not affect the release rate, but total amount released. Tissue integration and vascularization of carvacrol-loaded scaffolds were evaluated in a chorioallantoic membrane model (CAM) using a novel quantitative micro-computed tomography (micro-CT) analysis approach. The obtained results confirmed the CAM tissue ingrowth and new vessel formation within the porous structure of the scaffolds after 7 days of incubation, without leading to hemorrhagic or cytotoxic effects. The absence of lateral wall facilitated lateral integration of the scaffolds in the host tissue, although increased the anisotropy of the mechanical properties. Scaffolds loaded with carvacrol post-printing showed antibiofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa as observed in a decrease in CFU counting after biofilm detachment, changes in metabolic heat measured by calorimetry, and increased contact killing efficiency. In summary, this work demonstrated the feasibility of tuning carvacrol release rate and the amount released from PLA scaffolds to achieve antibiofilm protection without altering angiogenesis, which was mostly dependent on the perimeter density of the scaffoldsThis work was supported by MCIN/AEI/http://dx.doi.org/10.13039/501100011033 [PID2020-113881RB-I00], FEDER, and Xunta de Galicia [ED431C 2020/17, ED481D-2021-014]. Xián Farto-Vaamonde acknowledges Xunta de Galicia for a predoctoral research fellowship [ED481A-2018/073]S

Risk factors associated with Streptococcus suis cases on pig farms in Spain

Altres ajuts: acords transformatius de la UABBackground: Streptococcus suis can cause meningitis, polyarthritis and acute death in piglets. However, the risk factors associated with S. suis infection remain incompletely understood. Therefore, a longitudinal study was carried out, in which six batches from two Spanish pig farms with S. suis problems were repeatedly examined to determine possible risk factors. Methods: A prospective case-control study was conducted, and potential risk factors were evaluated using mixed-effects logistic regression models. The explanatory variables included: (a) concomitant pathogens; (b) biomarkers associated with stress, inflammation and oxidative status; (c) farm environmental factors; and (d) parity and S. suis presence in sows. Three models were built to study the effect of these variables, including two to assess the risk factors involved in the subsequent development of disease. Results: Risk factors for S. suis-associated disease included porcine reproductive and respiratory syndrome virus co-infection at weaning (odds ratio [OR] = 6.69), sow parity (OR = 0.71), haptoglobin level before weaning (OR = 1.01), relative humidity (OR = 1.11) and temperature (OR = 0.13). Limitations: Laboratory diagnosis was done at the batch level, with individual diagnosis based on clinical signs only. Conclusions: This study confirms the multifactorial nature of S. suis-associated disease, with both environmental factors and factors related to the host involved in disease development. Controlling these factors may, therefore, help prevent the appearance of disease

PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug