Computational modeling of epithelial wound healing: Short and long term chemo-mechanical mechanisms

During the lifetime of all living multicellular organisms, wounds in their tissues are frequently observed. Thecapability of closing those gaps is fundamental for a healthy development. If done deficiently, many diseasesmay occur from simple inflammation to tumor formation. The wound healing process in epithelial tissueoccurs in three different stages. The first one is the assembly of a supra-cellular actomyosin cable and itsmigration towards the wound edge, triggered by biochemical processes in which calcium plays a distinctiverole. How this process is orchestrated following damage remains unclear. Later, after its positioning, thecable contracts driving the tissue towards the gap and reducing the wound area. Finally, cell migrationtowards the interior of the wound ends up sealing the tissue. In this work, we make use of a mechanicalcontinuum model for the first two stages in order to developed and 2D finite element simulations within amonolithically fully implicit implementation. The model for the actomyosin cable formation involves thecoupling of transient calcium ions transport, with actin fibers and myosin motors recruitment and non-linearmechanical response of the tissue. The contraction stage, the active deformation of the previously formedactomyosin cable is taken into account. The relative motion of the myosin motors over the actin filaments ismodeled so there exists an active tissue contraction in the direction of those fibers. Upon implementation,the model is capable of performing a wide range of biophysical situations reported experimentally, as wedemonstrate in our numerical results. We have been able to rationalize through computational mechanicsthe firing of calcium in the wound right after damage infliction as well as the consequent formation of actinring, reproducing nicely what has been reported in biological literature. Thereafter, the numerical modelof acto-myosin contraction, fully integrated with the non-linear mechanics of the problem, correlates withthe mechanics of wound closure at the actin-ring contraction stage. More importantly, the approach is thefirst of its kind in the modeling of epithelial and embryonic cell layers, where a wide number of complexmechanics has been integrated and solved though computational methods in engineering. We believe thatthe simulations will help to unravel new insights in open questions of developmental biology.Peer ReviewedPostprint (author's final draft

Views from the Argentinian coast: The fishing community before metropolitan planning

En este artículo se abordan las problemáticas derivadas de los efectos de la desarticulación entre los procesos productivos locales y el emplazamiento de un conjunto de ensamblajes, que buscan rearticular los territorios con economías de flujos extractivos. El objetivo es analizar las miradas que, sobre un mismo sitio: la costa argentina, tienen actores de diversas escalas, y cómo ello interviene en la reconversión y redefinición urbana, metropolitana y territorial de ese espacio. En la metodología se combinan una aproximación histórica, con base en materiales documentales y periodísticos, y un trabajo etnográfico con entrevistas en profundidad en una comunidad pesquera del Remanso Valerio. El trabajo está dividido en cuatro miradas, con las que se reconstruyen los siguientes aspectos: la historia de ocupación del barrio; la relación de la población con el territorio y las actividades pesqueras; los impactos de la Hidrovía Paraná-Paraguay y el puente Rosario-Victoria; y la relación de la planificación estratégica metropolitana con la comunidad. Se concluye que los conflictos entre las perspectivas de la comunidad pesquera y la de quienes llevan a cabo la planificación metropolitana dependen de las asimetrías entre los actores y las escalas que intervienen en la organización de las miradas sobre la costa.In this article issues are addressed that are derived from the effects of the disarticulation of local productive processes and the emplacement of a collection of assemblages that seek to rearticulate territories through economies of extractive flows. The objective is to analyze views of a single site on the Argentinian coast with actors operating at multiple scales and how those actors influence the urban, metropolitan, and territorial reconversion and redefinition of that space. In the methodology, a historical approach is combined with documentary and journalistic materials and ethnographic work, with in-depth interviews in the fishing community of Remanso Valerio. The study is divided into four views, with which to reconstruct the following: The history of the occupancy of the neighborhood; the relation of the population with the territory and fishing activities; the impacts of the Paraná-Paraguay waterway and of the Rosario-Victoria bridge; and the relationship between the metropolitan strategic planning and the community. It is concluded that the conflicts between the perspective of the fishing community and that of the people carrying out metropolitan planning come from the asymmetries between actors and scales that shape views of the coast.Fil: Roldan, Diego Pablo. Universidad Nacional de Rosario. Facultad de Humanidades y Artes. Instituto de Estudios Críticos en Humanidades. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Estudios Críticos en Humanidades; ArgentinaFil: Arelovich, Lisandro. Universidad Nacional de Rosario. Facultad de Ciencias Políticas y Relaciones Internacionales. Instituto de Investigaciones; Argentin

The coastal-fluvial territoriality of the Paraná River in the province of Santa Fe (Argentina): An analysis of its actors, uses and appropriations in the context of the extraordinary downspout (2019-2023)

Este trabajo aborda la problemática de la territorialidad costero-fluvial en el delta medio del río Paraná. A partir de las afectaciones y las problemáticas derivadas de la situación de la bajante extraordinaria, producida entre 2019 y 2023, se reconstruye el sentido vertical de producción de los territorios. Asimismo, se utilizan las nociones de territorios hegemónicos, residuales, emergentes y alternativos para analizar la trama interactoral que se genera alrededor de las territorialidades costero-fluviales en el marco de la bajante extraordinaria. Para desarrollar esta aproximación analítica conformamos un corpus de documentos oficiales y publicaciones en diversos medios digitales para observar el recorrido y las tramitaciones de las diferentes afectaciones y problemáticas entre los actores involucrados. También, realizamos algunas entrevistas con informantes calificados para completar y triangular datos con especial relación a las problemáticas de los territorios de islas y los pescadores artesanales. El trabajo concluye que las formas que adopta la territorialidad costero-fluvial es el efecto de un complejo juego de fuerzas desplegado por los actores alrededor de las afectaciones y los modos de tramitar y resolver los distintos conflictos, suscitados por la fricción que las diversas concepciones del territorio fluvial generan normalmente y que se agudizan durante la bajante extraordinaria.Aquest treball aborda la problemàtica de la territorialitat costaner-fluvial en el delta mitjà del riu Paraná. A partir de les afectacions i les problemàtiques derivades de la situació de la baixant extraordinària, produïda entre 2019 i 2023, es reconstrueix el sentit vertical de producció dels territoris. Així mateix, s’utilitzen les nocions de territoris hegemònics, residuals, emergents i alternatius per a analitzar la trama interactoral que es genera al voltant de les territorialitats fluvials en el marc de la baixant extraordinària. Per a desenvolupar aquesta aproximació analítica conformem un corpus de documents oficials i publicacions en diversos mitjans digitals per a observar el recorregut i les tramitacions de les diferents afectacions i problemàtiques entre els actors involucrats. També, realitzem algunes entrevistes amb informants qualificats per a completar i triangular dades amb especial relació a les problemàtiques dels territoris d’illes i els pescadors artesanals. El treball conclou que les formes que adopta la territorialitat costaner-fluvial és l’efecte d’un complex joc de forces desplegat pels actors al voltant de les afectacions i els modes de tramitar i resoldre els diferents conflictes, suscitats per la fricció que les diverses concepcions del territori fluvial generen normalment i que s’aguditzen durant la baixant extraordinària.Fil: Arelovich, Lisandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Humanidades y Artes; ArgentinaFil: Urcola, Marcos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Humanidades y Artes; ArgentinaFil: Roldan, Diego Pablo. Universidad Nacional de Rosario. Facultad de Humanidades y Artes. Instituto de Estudios Críticos en Humanidades. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Estudios Críticos en Humanidades; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Políticas y Relaciones Internacionales. Escuela de Relaciones Internacionales; Argentin

Computational modeling of epithelial wound healing: Short and long term chemo-mechanical mechanisms

During the lifetime of all living multicellular organisms, wounds in their tissues are frequently observed. Thecapability of closing those gaps is fundamental for a healthy development. If done deficiently, many diseasesmay occur from simple inflammation to tumor formation. The wound healing process in epithelial tissueoccurs in three different stages. The first one is the assembly of a supra-cellular actomyosin cable and itsmigration towards the wound edge, triggered by biochemical processes in which calcium plays a distinctiverole. How this process is orchestrated following damage remains unclear. Later, after its positioning, thecable contracts driving the tissue towards the gap and reducing the wound area. Finally, cell migrationtowards the interior of the wound ends up sealing the tissue. In this work, we make use of a mechanicalcontinuum model for the first two stages in order to developed and 2D finite element simulations within amonolithically fully implicit implementation. The model for the actomyosin cable formation involves thecoupling of transient calcium ions transport, with actin fibers and myosin motors recruitment and non-linearmechanical response of the tissue. The contraction stage, the active deformation of the previously formedactomyosin cable is taken into account. The relative motion of the myosin motors over the actin filaments ismodeled so there exists an active tissue contraction in the direction of those fibers. Upon implementation,the model is capable of performing a wide range of biophysical situations reported experimentally, as wedemonstrate in our numerical results. We have been able to rationalize through computational mechanicsthe firing of calcium in the wound right after damage infliction as well as the consequent formation of actinring, reproducing nicely what has been reported in biological literature. Thereafter, the numerical modelof acto-myosin contraction, fully integrated with the non-linear mechanics of the problem, correlates withthe mechanics of wound closure at the actin-ring contraction stage. More importantly, the approach is thefirst of its kind in the modeling of epithelial and embryonic cell layers, where a wide number of complexmechanics has been integrated and solved though computational methods in engineering. We believe thatthe simulations will help to unravel new insights in open questions of developmental biology.Peer Reviewe

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2-6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society