A Credibility Assessment Plan for an In Silico Model that Predicts the Dose–Response Relationship of New Tuberculosis Treatments

Tuberculosis is one of the leading causes of death in several developing countries and a public health emergency of international concern. In Silico Trials can be used to support innovation in the context of drug development reducing the duration and the cost of the clinical experimentations, a particularly desirable goal for diseases such as tuberculosis. The agent-based Universal Immune System Simulator was used to develop an In Silico Trials environment that can predict the dose–response of new therapeutic vaccines against pulmonary tuberculosis, supporting the optimal design of clinical trials. But before such in silico methodology can be used in the evaluation of new treatments, it is mandatory to assess the credibility of this predictive model. This study presents a risk-informed credibility assessment plan inspired by the ASME V&V 40‐2018 technical standard. Based on the selected context of use and regulatory impact of the technology, a detailed risk analysis is described together with the definition of all the verification and validation activities and related acceptability criteria. The work provides an example of the first steps required for the regulatory evaluation of an agent-based model used in the context of drug development

Genetic hypervariability of a Northeastern Atlantic venomous rockfish

Background: Understanding the interplay between climate and current and historical factors shaping genetic diversity is pivotal to infer changes in marine species range and communities’ composition. A hylogeographical break between the Atlantic and the Mediterranean has been documented for several marine organisms, translating into limited dispersal between the two basins. Methods: In this study, we screened the intraspecific diversity of 150 individuals of the Madeira rockfish (Scorpaena maderensis) across its distributional range (seven sampling locations in the Atlantic and Mediterranean basins) using the mitochondrial control region and the nuclear S7 first intron. Results: The present work is the most comprehensive study done for this species, yielding no genetic structure across sampled locations and no detectable Atlantic-Mediterranean break in connectivity. Our results reveal deep and hyper-diverse bush-like genealogies with large numbers of singletons and very few shared haplotypes. The genetic hyper-diversity found for the Madeira rockfish is relatively uncommon in rocky coastal species, whose dispersal capability is limited by local oceanographic patterns. The effect of climate warming on the distribution of the species is discussed.MARE/UIDB/MAR/04292/2020info:eu-repo/semantics/publishedVersio

Características geoquímicas de las cuñas de hielo en Puerto Deseado (Santa Cruz, Argentina): implicancias paleoambientales y cronológicas

Ground wedge structures of cryogenic origin are common in the Quaternary sediments along the coast of the Patagonia, and their formation is related to climatic cold events experienced by this area in the Late Quaternary. The infilling sediments of two wedges generations were analyzed in the area of Puerto Deseado. Bulk chemistry (major elements), X-ray diffraction (XRD), morphoscopic observations with Scanning Electronic Microscope (SEM) and chemical analyses of volcanic glass shards were undertaken to provide indications about infilling sediment provenience, along with chronological constraint for wedge formation. Bulk chemistry and XRD patterns indicate a significant SiO2- enriched composition of the sediment infilling compared to the most of the loess deposits of the North Argentina and the present day dust originated in Patagonia. This was interpreted as due to the nature of the bedrock present over the Deseado Massif. SEM morphoscopic characteristics of glass shards evidence typical aeolian reworking features, with impact structures and indented edges of the volcanic fragments. Chemical analyses of the glass shards indicate that they were probably generated by the H0 eruption (17,300-17,400 cal yr BP) of the Hudson volcano. Volcanological data indicate that H0 eruption dispersed toward NE, but volcanic glasses were available for reworking due to a WNW component in the western wind direction. Over the Deseado Massif structural high the glass shards mixed with sediments enriched in SiO2, and were eventually deflated further to SE reaching the present coastal area and infilling the frost cracks. The age of the glass shards (17,300-17,400 cal yr BP) and that of the sandy layer affected by cryogenic structures (14,670±750 yr BP) well constrain to the Late Glacial both wedge generations.Las cuñas de hielo son estructuras comunes en sedimentos cuaternarios a lo largo de la costa patagónica, y su formación está relacionada con eventos climáticos fríos experimentados en esta área en el Cuaternario Tardío. Se analizaron sedimentos que rellenan dos generaciones de cuñas de hielo en la zona de Puerto Deseado. Análisis químicos de elementos mayores, difractometría de rayos X (DRX), observaciones con microscopio electrónico de barrido (SEM) y análisis químico de fragmentos de vidrio volcánico contenidos en el sedimento que rellena las cuñas proporcionaron información sobre la precedencia del relleno, además de inferir antecedentes cronológicos sobre su formación. La composición química del sedimento y la difracción de rayos X indican una composición enriquecida en SiO2 en comparación con la mayoría de los depósitos de loess del norte de Argentina y el polvo actual originado en la Patagonia. Esto fue interpretado como producto de la influencia de las rocas que constituyen el macizo del Deseado. Las características morfológicas de los fragmentos de vidrio evidencian rasgos típicos de retrabajo eólico, con presencia de estructuras de impacto y bordes dentados. Los análisis químicos de los fragmentos de vidrio son compatibles con un origen en la erupción H0 (17.300-17.400 cal yr BP) del volcán Hudson. Datos volcanológicos indican que la erupción H0 originó una pluma de dispersión hacia el NE. El material volcánico dispersado por esta erupción quedó disponible para ser retrabajado por una componente WNW de los vientos del W dominantes en la zona. Sobre el macizo del Deseado, los fragmentos de vidrio se mezclaron con sedimentos ricos en SiO2 y fueron adicionalmente, enriquecidos en este elemento hasta alcanzar el área de costa actual, rellenando las cuñas de hielo. La edad de los fragmentos de vidrio (17.300-17.400 cal yr BP) y de la capa arenosa afectada por las estructuras criogénicas (14.670±750 años BP) limitan al glacial tardío la formación de ambas generaciones de cuñas.Centro de Estudios Integrales de la Dinámica Exógen

Niveles altos del mar durante el Último Máximo Interglacial deducidos mediante muescas de abrasión y márgenes internos de terrazas marinas en Puerto Deseado, Provincia de Santa Cruz, Argentina

A detailed geomorphological survey was undertaken in the area of Puerto Deseado (Santa Cruz Province, Argentina) to reconstruct the Relative Sea-level (RSL) position during the Last Interglacial highstand. The presence of active and well-preserved abrasive notches and inner margins of terraces related to the MIS5e and to the Holocene, measured with DGPS, allowed to accurately estimate the RSL change from the present to the MIS5e highstand at ca. 21 m. The geomorphological and geochronological analyses support the notion of the presence of a significant regional tectonic uplift in the Atlantic Patagonia, which can be locally estimated at ca. 0.12 mm/yr.Se realizó un estudio geomorfológico detallado en la zona de Puerto Deseado (provincia de Santa Cruz, Argentina) para reconstruir la posición relativa del nivel (RNM) del mar durante el Último Máximo Interglacial. La presencia de muescas de abrasión activas y bien conservadas, y la posición de los márgenes internos de las terrazas relacionadas con el MIS5e y el Holoceno, medido con GPS diferencial, permitió estimar con precisión el cambio RNM desde el presente hasta la transgresión MIS5e en aproximadamente 21 m. Los análisis geomorfológicos y geocronológicos sustentan la noción de la presencia de un significativo levantamiento tectónico regional en la Patagonia Atlántica, que puede estimarse localmente en alrededor de 0,12 mm/año.Facultad de Ciencias Naturales y Muse

Mid-Holocene relative sea-level changes along Atlantic Patagonia: new data from Camarones, Chubut, Argentina

This paper concerns the relative sea-level changes associated with the Atlantic Patagonian coast derived from sea-level index points whose elevation was determined by a differential global position system (DGPS). Bio encrustations from outcrops located near Camarones, Chubut, Argentina, consist of autochthonous deposits characterized by Austromegabalanus psittacus (Molina, 1782), encrusting acer vulinid foraminifera, coralline red algae and bryozoans. The association of the different organisms is interpreted as being associated with an intertidal environment, and they have been used as index points to establish the relative sea-level position. The main conclusion is that the relative sea-level between c. 7000 and 5300 cal. yr BP was in the range ofc. 2?4 m a.s.l., with a mean value of c. 3.5 m a.s.l. Our data seem to support the existence of different rates of relative sea-level fall in different sectors of Atlantic Patagonia during the Holocene and highlight the importance of a more precise and accurate relative sea-level estimation by producing new data and revisiting the indicative meaning of most of the indicators so far used in the area.Facultad de Ciencias Naturales y Muse

Suppression Mental Questionnaire App: a mobile web service-based application for automated real-time evaluation of adolescent and adult suppression

The Suppression Mental Questionnaire System (mobile App, Web-Services, Cloud...) acts as a bridge among dynamic psychology, the cognitive studies, and modern information and telecommunication technologies (ICT). The adoption of digital tools speeds clinical investigations on defense mechanisms and makes clinical trials easier by reducing needed effort for manual scoring. It also enables faster and deeper research practices, also more appropriate to the times by enabling the real-time transfer of the results to digital archives  for statistical and psychometrical purposes. Reliability of the scale was evaluated by using Cronbach's alpha; this numerical coefficient of reliability was calculated for the three factors and for the two psychodiagnostic tools. The digital tool melts together scalability and availability provided by the mobile application, power and flexibility provided by Web 2.0 portal. The statistical analysis show a good reliability of the scale and of different factors. Differences related to the factors are considered possible on the basis of the current literature.Mobile Operating Systems, Internet, Web 2.0, and the considerable computing capabilities provided by Clouds are powerful combinations of tools able to provide real-time Open Data/Results to scientists and users, and to spread up the use of the questionnaire all over the world

Correction to: Human migration: the big data perspective

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