High Speed Finish Turning of Inconel 718 Using PCBN Tools under Dry Conditions

Inconel 718 is a superalloy, considered one of the least machinable materials. Tools must withstand a high level of temperatures and pressures in a very localized area, the abrasiveness of the hard carbides contained in the Inconel 718 microstructure and the adhesion tendency during its machining. Mechanical properties along with the low thermal conductivity become an important issue for the tool wear. The finishing operations for Inconel 718 are usually performed after solution heat treatment and age hardening of the material to give the superalloy a higher level of hardness. Carbide tools, cutting fluid (at normal or high pressures) and low cutting speed are the main recommendations for finish turning of Inconel 718. However, dry machining is preferable to the use of cutting fluids, because of its lower environmental impact and cost. Previous research has concluded that the elimination of cutting fluid in these processes is feasible when using hard carbide tools. Recent development of new PCBN (Polycrystalline Cubic Boron Nitride) grades for cutting tools with higher tenacity has allowed the application of these tool grades in the finishing operations of Inconel 718. This work studies the performance of commercial PCBN tools from four different tool manufacturers as well as an additional grade with equivalent performance during finish turning of Inconel 718 under dry conditions. Wear tests were carried out with different cutting conditions, determining the evolution of machining forces, surface roughness and tool wear. It is concluded that it is not industrially viable the high-speed finishing of Inconel 718 in a dry environment.This work was supported by the Spanish Ministry of Economy and Competitiveness and FEDER program under grant DPI2014-56137-C2-2-R

Role-shifting threads: Increasing OpenMP malleability to address load imbalance at MPI and OpenMP

This paper presents the evolution of the free agent threads for OpenMP to the new role-shifting threads model and their integration with the Dynamic Load Balancing (DLB) library. We demonstrate how free agent threads can improve resource utilization in OpenMP applications with load imbalance in their nested parallel regions. We also demonstrate how DLB efficiently manages the malleability exposed by the role-shifting threads to address load imbalance issues. We use three real-world scientific applications, one of them to demonstrate that free agents alone can improve the OpenMP model without external tools, and two other MPI+OpenMP applications, one of them with a coupling case, to illustrate the potential of the free agent threads’ malleability with an external resource manager to increase the efficiency of the system. In addition, we demonstrate that the new implementation is more usable than the former one, letting the runtime system automatically make decisions that were made by the programmer previously. All software is released open-source.This work has received funding from the DEEP Projects, at the European Commission’s FP7, H2020, and EuroHPC Programmes, under Grant Agreements 287530, 610476, 754304, and 955606. The PCI2021-121958 financed by the Spanish State Research Agency - Ministry of Science and Innovation. And it also has the support of the Spanish Ministry of Science and Innovation (Computacion de Altas Prestaciones VIII: PID2019-107255GB).Peer ReviewedPostprint (author's final draft

Meta-Analysis and Validation of a Colorectal Cancer Risk Prediction Model Using Deep Sequenced Fecal Metagenomes

Simple Summary Colorectal cancer (CRC) is the third most common cancer in the world. The gut microbiome, which includes a collection of microbes, is a potential modifiable risk factor. The study of the microbiome is complex and many issues remain unsolved despite the scientific efforts that have been recently made. The present study aimed to build a CRC predictive model performing a meta-analyses of previously published shotgun metagenomics data, and to validate it in a new study. For that purpose, 156 participants of a CRC screening program were recruited, with an even distribution of CRCs, high-risk colonic precancerous lesions, and a control group with normal colonic mucosa. We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions. This suggests that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. The gut microbiome is a potential modifiable risk factor for colorectal cancer (CRC). We re-analyzed all eight previously published stool sequencing data and conducted an MWAS meta-analysis. We used cross-validated LASSO predictive models to identify a microbiome signature for predicting the risk of CRC and precancerous lesions. These models were validated in a new study, Colorectal Cancer Screening (COLSCREEN), including 156 participants that were recruited in a CRC screening context. The MWAS meta-analysis identified 95 bacterial species that were statistically significantly associated with CRC (FDR < 0.05). The LASSO CRC predictive model obtained an area under the receiver operating characteristic curve (aROC) of 0.81 (95%CI: 0.78-0.83) and the validation in the COLSCREEN dataset was 0.75 (95%CI: 0.66-0.84). This model selected a total of 32 species. The aROC of this CRC-trained model to predict precancerous lesions was 0.52 (95%CI: 0.41-0.63). We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions, suggesting that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. Further studies should focus on CRC as well as precancerous lesions with the intent to implement a microbiome signature in CRC screening programs

Homérica: estudiar y vivir el mundo griego (2020-2021)

Formación del alumno en la Antigüedad Clásica en doble orientación didáctica: teórica y teatral-artística, en conjunción. La teórica consiste en jornadas de conferencias y la práctica en un montaje teatral mitológico, a cargo de alumnos y profesores

A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care

15 p.-3 fig.-3 tab.Introduction:The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion.Patients and methods:The efficacy of oral domperidone plus standard of care (SOC; n = 87) versus placebo plus SOC (n = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes.Results:A significant reduction in the viral load was observed (p < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized.Conclusion: Results do not prove the use of domperidone as antiviral in patients with COVID-19.This research was funded by CSIC (grant no. PIE 201980E024) and by the European Commission: NextGeneration EU (Regulation EU 2020/2094) through CSIC’s Global Health Platform (PTI Salud Global). The study sponsor was Agencia Estatal Consejo Superior de Investigaciones Científicas, M.P. (CSIC), Madrid, Spain. The sponsor was involved in the design, data interpretation, manuscript review and the decision to submit the article for publication.Peer reviewe

Landscape, orientation and celestial phenomena on the ‘Coast of Death’ of NW Iberia

This paper investigates the land- and sky-scapes surrounding the dolmens of Costa da Morte (Coast of Death), Galicia. Having uncovered previously that the location of megalithic monuments in this coherent area of the south-eastern side of the European Atlantic Façade connects to complex topographical features, we now show how this chosen topography connects to astronomical phenomena. We will see how the detailed shape of the horizon coincides with specific risings and settings of the Sun and Moon, providing further support for the notion that the creators of these monuments selectively drew upon a variety of features found in their natural world.Peer reviewe

Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation

PMCID: PMC3545406.-- et al.The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre-associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.National Institutes of Health (NIH) grants NIH CA109335 and NIH CA122105; the Dwoskin Family Foundations; NIH P01 CA34233 FEDER and by MICINN (SAF2009-08803 and SAF2012-32810 to ISG); Junta de Castilla y León (REF. CSI007A11-2 and Proyecto Biomedicina 2009-2010); MEC OncoBIO Consolider-Ingenio 2010 (Ref. CSD2007-0017); Sandra Ibarra Foundation; Group of Excellence Grant (GR15) from Junta de Castilla y Leon; the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Programme)Peer Reviewe

A Remote Nutritional Intervention to Change the Dietary Habits of Patients Undergoing Ablation of Atrial Fibrillation: Randomized Controlled Trial

Background: The Prevention With Mediterranean Diet (PREDIMED) trial supported the effectiveness of a nutritional intervention conducted by a dietitian to prevent cardiovascular disease. However, the effect of a remote intervention to follow the Mediterranean diet has been less explored. Objective: This study aims to assess the effectiveness of a remotely provided Mediterranean diet–based nutritional intervention in obtaining favorable dietary changes in the context of a secondary prevention trial of atrial fibrillation (AF). Methods: The PREvention of recurrent arrhythmias with Mediterranean diet (PREDIMAR) study is a 2-year multicenter, randomized, controlled, single-blinded trial to assess the effect of the Mediterranean diet enriched with extra virgin olive oil (EVOO) on the prevention of atrial tachyarrhythmia recurrence after catheter ablation. Participants in sinus rhythm after ablation were randomly assigned to an intervention group (Mediterranean diet enriched with EVOO) or a control group (usual clinical care). The remote nutritional intervention included phone contacts (1 per 3 months) and web-based interventions with provision of dietary recommendations, and participants had access to a web page, a mobile app, and printed resources. The information is divided into 6 areas: Recommended foods, Menus, News and Online resources, Practical tips, Mediterranean diet classroom, and Your personal experience. At baseline and at 1-year and 2-year follow-up, the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire and a semiquantitative food frequency questionnaire were collected by a dietitian by phone. Results: A total of 720 subjects were randomized (365 to the intervention group, 355 to the control group). Up to September 2020, 560 subjects completed the first year (560/574, retention rate 95.6%) and 304 completed the second year (304/322, retention rate 94.4%) of the intervention. After 24 months of follow-up, increased adherence to the Mediterranean diet was observed in both groups, but the improvement was significantly higher in the intervention group than in the control group (net between-group difference: 1.8 points in the MEDAS questionnaire (95% CI 1.4-2.2; P<.001). Compared with the control group, the Mediterranean diet intervention group showed a significant increase in the consumption of fruits (P<.001), olive oil (P<.001), whole grain cereals (P=.002), pulses (P<.001), nuts (P<.001), white fish (P<.001), fatty fish (P<.001), and white meat (P=.007), and a significant reduction in refined cereals (P<.001), red and processed meat (P<.001), and sweets (P<.001) at 2 years of intervention. In terms of nutrients, the intervention group significantly increased their intake of omega-3 (P<.001) and fiber (P<.001), and they decreased their intake of carbohydrates (P=.02) and saturated fatty acids (P<.001) compared with the control group. Conclusions: The remote nutritional intervention using a website and phone calls seems to be effective in increasing adherence to the Mediterranean diet pattern among AF patients treated with catheter ablation.This work was funded by the Spanish Government Official Agency for funding biomedical research—Instituto de Salud Carlos III (ISCIII), with competitive grants through the Fondo de Investigación Sanitaria y Fondo Europeo de Desarrollo Regional (PI17/00718, PI17/00748, PI17/01870), the Regional Government of Navarra (46/2016), and the Spanish Society of Cardiology (FEC/2016).Ye