One-dimensional migration of olfactory ensheathing cells on synthetic materials: Experimental and numerical characterization

Olfactory ensheathing cells (OECs) are of great interest for regenerative purposes since they are believed to aid axonal growth. With the view set on the strategies to achieve reconnection between neuronal structures, it is of great importance to characterize the behaviour of these cells on long thread-like structures that may efficiently guide cell spread in a targeted way. Here, rat OECs were studied on polycaprolactone (PCL) long monofilaments, on long bars and on discs. PCL turns out to be an excellent substrate for OECs. The cells cover long distances along the monofilaments and colonize completely these struc- tures. With the help of a one-dimensional (1D) analytical model, a migration coefficient, a net proliferation rate constant and the fraction of all cells which undergo migration were obtained. The separate effect of the three phenomena summarized by these parameters on the colo- nization patterns of the 1D path was qualitatively dis- cussed. Other features of interest were also determined, such as the speed of the advance front of colonization and the order of the kinetics of net cell proliferation. Charac- terizing migration by means of these quantities may be useful for comparing and predicting features of the colo- nization process (such as times, patterns, advance fronts and proportion of motile cells) of different cell substrate combinations.Support of the Spanish Science & Innovation Ministery through project MAT2008-06434 is acknowledged. MMP and CMR acknowledge partial funding through the "Convenio de Colaboracion para la Investigacion Basica y Traslacional en Medicina Regenerativa" between the Instituto Nacional de Salud Carlos III, the Conselleria de Sanidad of the Generalitat Valenciana and the Foundation Centro de Investigacion Principe Felipe.Perez Garnes, M.; Martínez Ramos, C.; Barcia, JA.; Escobar Ivirico, JL.; Gomez Pinedo, UA.; Vallés Lluch, A.; Monleón Pradas, M. (2013). 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On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models

[EN] In order to be reusable, history-based feature-based parametric CAD models must reliably allow for modifications while maintaining their original design intent. In this paper, we demonstrate that relations that fix the location of geometric entities relative to the reference system produce inflexible profiles that reduce model reusability. We present the results of an experiment where novice students and expert CAD users performed a series of modifications in different versions of the same 2D profile, each defined with an increasingly higher number of fix geometric constraints. Results show that the amount of fix constraints in a 2D profile correlates with the time required to complete reusability tasks, i.e., the higher the number of fix constraints in a 2D profile, the less flexible and adaptable the profile becomes to changes. In addition, a pilot software tool to automatically track this type of constraints was developed and tested. Results suggest that the detection of fix constraint overuse may result in a new metric to assess poor quality models with low reusability. The tool provides immediate feedback for preventing high semantic level quality errors, and assistance to CAD users. Finally, suggestions are introduced on how to convert fix constraints in 2D profiles into a negative metric of 3D model quality.The authors would like to thank Raquel Plumed for her support in the statistical analysis. This work has been partially funded by Grant UJI-A02017-15 (Universitat Jaume I) and DPI201784526-R (MINECO/AEI/FEDER, UE), project CAL-MBE. The authors also wish to thank the editor and reviewers for their valuable comments and suggestions that helped us improve the quality of the paper.González-Lluch, C.; Company, P.; Contero, M.; Pérez Lopez, DC.; Camba, JD. (2019). On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models. 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Graph-based simplification of feature-based three-dimensional computer-aided design models for preserving connectivity. Journal of Computing and Information Science in Engineering, 15(3), 031010. https://doi.org/10.1115/1.4030748 .Leea, J. Y., & Kimb, K. (1998). A 2-D geometric constraint solver using DOF-based graph reduction. Computer-Aided Design, 30(11), 883–896. https://doi.org/10.1016/S0010-4485(98)00045-1 .Mata Burgarolas, N. (1997). Solving incidence and tangency constraints in 2D. Technical report LSI-97-3R, Departament LiSI, Universitat Politècnica de Catalunya.Petrina, S. (2003). Two cultures of technical courses and discourses: The case of computer aided design. International Journal of Technology and Design Education, 13, 47–73.Race, P. (2001). The lecturers toolkit—A practical guide to learning, teaching and assessment. Great Britain: Glasgow.Red, E., French, D., Jensen, G., Walker, S. S., & Madsen, P. (2013). 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Difficulties with the novices’ comprehension of the computer-aided design (CAD) interface: Understanding visual representations of CAD tools. Journal of Engineering Design, 14(2), 169–185. https://doi.org/10.1080/0954482031000091491

Critical Elements in Supergene Phosphates: The Example of the Weathering Profile at the Gavà Neolithic Mines, Catalonia, Spain

The essential role of Critical Elements (CE) in 21st century economy has led to an increasing demand of these metals and promotes the exploration of non-conventional deposits such as weathering profiles. The present work is focused on the study of a weathering profile located at the Archaeological Park of the Gavà Neolithic Mines, Barcelona, Catalonia, Spain. In the Gavà deposit, acid and oxidising meteoric fluids generated intense weathering during the early Pleistocene, affecting series of Llandoverian black shales and associated syn-sedimentary phosphates. The circulation of these acid fluids at deeper levels of the profile generated supergene vein-like mineralisations comprised of secondary phosphates (e.g., variscite, perhamite, crandallite, phosphosiderite) and sulphates (e.g., jarosite, alunite). This supergene mineralisation is significantly enriched in certain CE (e.g., Ga, Sc, REE, In, Co and Sb) that were mobilised from host rock components and later hosted in the crystal lattice of supergene minerals. Weathering processes and corresponding supergene enrichment of CE at the Gavà deposit could be used as an example to determine exploration guidelines of CE in weathering profiles and associated supergene phosphates worldwide

Revisiting the design intent concept in the context of mechanical CAD education

[EN] Design intent is generally understood simply as a CAD model¿s anticipated behavior when altered. However, this representation provides a simplified view of the model¿s construction and purpose, which may hinder its general understanding and future reusability. Our vision is that design intent communication may be improved by recognizing the multifaceted nature of design intent, and by instructing users to convey each facet of design intent through the better-fitted CAD resource. This paper reviews the current understanding of design intent and its relationship to design rationale and builds on the idea that communication of design intent conveyed via CAD models can be satisfied at three levels provided that specialized instruction is used to instruct users in selection of the most suitable level for each intent.Otey, J.; Company, P.; Contero, M.; Camba, J. (2018). Revisiting the design intent concept in the context of mechanical CAD education. Computer-Aided Design and Applications. 15(1):47-60. https://doi.org/10.1080/16864360.2017.1353733S476015

Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01)

Altres ajuts: Agustí Barnadas: Honoraria: Pfizer. Consulting or Advisory Role: Pfizer, Novartis, Eli Lilly. Speakers'Bureau: Roche, Pfizer, Novartis, Genomic Health International. Travel, Accommodations, Expenses: Roche, Pfizer; Miguel A. Seguí: Consulting or Advisory Role: Roche, Pfizer, Novartis, Amgen, Eisai, Eli Lilly. Speakers' Bureau: Roche, Pfizer, Amgen. Research Funding: Roche (Inst), Novartis (Inst). Travel, Accommodations, Expenses: Roche, Pfizer, Novartis, Amgen.Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. Eligible patients were those with operable, node-positive-or node negative with tumor 1 cm or greater-TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P =.136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P =.0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P =.0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19 : a multicentre, randomised, double-blind, non-inferiority phase IIb trial

A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with , . From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U

Defining the characteristics and expectations of fluid bolus therapy: a worldwide perspective

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes.Facultad de Ciencias Médica

Excavated architecture in the mediterranean: the CHRIMA project.

El proyecto CHRIMA -Cultural rupestrian heritage in the circum-mediterranean Area ¿ common identity new perspective-, financiado con fondos del proyecto CULTURE de la Comunidad Europea, representa una propuesta de coordinación por parte de entidades de investigación de cinco países ribereños del Mediterráneo ¿Italia, España, Turquía, Francia y Grecia- para desarrollar una propuesta de censo, análisis, levantamiento gráfico y puesta en valor, del vasto patrimonio arquitectónico excavado presente en todos ellos. Las actividades desarrolladas han evidenciado que el vivir en espacios excavados es un fenómeno transversal e intercultural, desarrollado simultáneamente y con similares características en todos los países estudiados. El estudio completo y comparativo, desarrollado por vez primera de forma integrada en los cinco países implicados, demuestra que este tipo de arquitecturas supone una característica cultural común a todos los pueblos del Mediterráneo, asentada sobre unas características geológicas y climáticas idóneas, pero que en el fondo responde a necesidades comunes y a similares estructuras socio-culturales. Además del censo global y de la sistematización coordinada del catálogo desarrollado, se ha trabajado en profundidad en un número limitado de enclaves, elegios en función de sus características, y en los que se ha desarrollado un levantamiento analítico preciso, ejecutado con escáner-láser y en los cuales se ha reconstruido virtualmente las características espaciales. La atención se ha centrado en algunos enclaves de la provincia de Taranto (Italia), en el pueblo de Ortahisar en la Cappadocia (Turquía), en la Comunidad Valencia (España), y en el valle del Lora (Francia)The CHRIMA project - Cultural rupestrian heritage in the circum-Mediterranean Area ¿ common identity new perspective- is funded by the European Community CULTURE project and proposes coordination by research institutions from five countries bordering the Mediterranean, Italy, Spain, Turkey, France and Greece, to develop a proposal for a census, graphic analysis, survey and assessment of the vast excavated architectural heritage present in all of them. The common activities undertaken have born witness that living in carved out spaces is an intercultural and transversal phenomenon, simultaneously developed and with similar features in all the countries under study. Thexhaustive and comparative analyses, which were developed in an integrated way in the five countries for the first time, shows that such architecture typology features common cultural characteristics among all Mediterranean peoples that settled in ideal geological and climatic characteristics, but which in the end correspond to common socio-cultural structures and similar necessities. In addition to the global census and the coordinated systematization of the developed catalog, further detailed work was carried out on a limited number of sites chosen for their characteristics, and where precise analytical survey has been performed with the help of laser-scanner. Later, the spatial characteristics of these chosen sites have been virtually reconstructed. We have focused on some enclaves in the province of Taranto (Italy), in the village eof Ortahisar in Cappadocia (Turkey), in the Community of Valencia (Spain), and in the valley of Loire (France).Llopis Verdú, J.; Crescenzi, C.; Barros Da Rocha E Costa, HA.; García Codoñer, Á.; Torres Barchino, AM.; Serra Lluch, JDR.; Higón Calvet, JL. (2011). La arquitectura excavada en el mediterráneo. El proyecto CHRIMA. Arché. (6):75-86. http://hdl.handle.net/10251/330507586