El problema de Behrens-Fisher en la investigación biomédica. Análisis crítico de un estudio clínico mediante simulación

En el artículo se hace una revisión del problema de Behrens-Fisher, discutiendo los fundamentos inferenciales asociados a la dificultad de su resolución y exponiendo las soluciones prácticas más comunes, juntamente con una nueva solución basada en conceptos de geometría diferencial. A continuación, se realiza un estudio crítico de una investigación biomédica en donde las verdaderas probabilidades de error son distintas de las supuestas debido a que se ignoran probables diferencias entre las varianzas. En dicha investigación se rechazó la hipótesis nula de igualdad de medias (p < 0.01 ), si bien, la verdadera probabilidad de error de tipo I para valores próximos a los muestrales parece ser otra. Con este fin, se realiza un estudio de Monte Cario para obtener estas estimaciones según se utilice el test t de Student de comparación de medias o diferentes soluciones más apropiadas para el problema de Behrens-Fisher. En este estudio de simulación se usa una técnica de reducción de la varianza específica para variables de respuesta dicotómica tales como contrastes de hipótesis (aceptar, no aceptar la hipótesis nula). Se presenta brevemente esta técnica y se ilustra como se diseña la simulación de acuerdo con la mismaPeer Reviewe

Cenozoic deformation of Iberia: a model for intraplate mountain building and basin development based on analogue modelling

Inferences from analogue models support lithospheric folding as the primary response to large-scale shortening manifested in the present day topography of Iberia. This process was active from the late Oligocene-early Miocene during the Alpine orogeny and was probably enhanced by reactivation of inherited Variscan faults. The modeling results confirm the dependence of fold wavelength on convergence rate and hence the strength of the layers of the lithosphere such that fold wavelength is longest for fast convergence rates favoring whole lithosphere folding. Folding is associated with the formation of dominantly pop-up type mountain ranges in the brittle crust and thickening of the ductile layers in the synforms of the buckle folds by flow. The mountain ranges are represented by upper crustal pop-ups forming the main topographic relief. The wavelengths of the topographic uplifts, both, in model and nature suggest mechanical decoupling between crust and mantle. Moreover, our modeling results suggest that buckling in Iberia took place under rheological conditions where the lithospheric mantle is stronger than the lower crust. The presence of an indenter, inducing oblique shortening in response to the opening of the King's Trough in the north western corner of the Atlantic Iberian margin controls the spacing and obliquity of structures. This leads to the transfer of the deformation from the moving walls towards the inner part of the model, creating oblique structures in both brittle and ductile layers. The effect of the indenter, together with an increase on the convergence rate produced more complex brittle structures. These results show close similarities to observations on the general shape and distribution of mountain ranges and basins in Iberia, including the Spanish Central System and Toledo Mountains.Peer reviewe

Inventory of Geological Sites of Interest in the Canary Islands

En el marco de proyecto de investigación LIGCANARIAS (2018-2021) se ha realizado el Inventario de Lugares de Interés Geológico de las Islas Canarias, que forma parte del Inventario Español de Lugares de Interés Geológico (IELIG) para el dominio de este archipiélago. El inventario ha empleado la metodología del IELIG adaptada a un dominio geológico eminentemente volcánico, partiendo de los contextos geológicos regionales. Consta de 300 LIG: 53 en Gran Canaria, 47 en Tenerife, 54 en Lanzarote y Archipiélago Chinijo, 40 en Fuerteventura, 29 en La Palma, 23 en La Gomera y 21 en El Hierro. La principal novedad con respecto a los inventarios en otros dominios geológicos es la identificación de 33 LIG submarinos.Within the framework of the LIGCANARIAS research project (2018-2021), the Inventory of Geological Sites of Interest of the Canary Islands has been carried out, which is part of the Spanish Inventory of Places of Geological Interest (IELIG) for the domain of this archipelago. The inventory has used the IELIG methodology adapted to an eminently volcanic geological domain, based on regional geological frameworks. It consists of 300 geosites: 53 in Gran Canaria, 47 in Tenerife, 54 in Lanzarote and Chinijo Archipelago, 40 in Fuerteventura, 29 in La Palma, 23 in La Gomera and 21 in El Hierro. The main novelty with respect to the inventories in other geological domains is the identification of 33 submarine geosites.Depto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEAgencia Canaria de Investigación, Innovación y Sociedad de la Informaciónpu

IVRIPARC project: a method for assessing the impact of global change on geoheritage of the Canary Islands national parks (Spain)

El patrimonio geológico y la geodiversidad de los parques nacionales contribuyen, junto con la biodiversidad, para que sean espacios naturales protegidos únicos en el país, pero también únicos a nivel mundial. El patrimonio geológico es de carácter no renovable, de tal forma que, si se pierden o degradan, lo hacen para siempre. Ante el escenario del cambio global, el patrimonio geológico de los parques nacionales canarios es muy vulnerable a los impactos rovocados por los cambios en la temperatura, avenidas torrenciales, tormentas extremas, sequías, desertificación y ascenso del nivel del mar, fundamentalmente, y a los impactos derivados de la actividad humana. Estos fenómenos provocan la activación de procesos geológicos que afectan directamente a su conservación, de tal forma que es necesario identificar los Lugares de Interés Geológico más amenazados, evaluar su incidencia y establecer los indicadores a escala de cada parque nacional para realizar su seguimiento. Conocer el estado de conservación actual, su vulnerabilidad y sus amenazas directas contribuirá a la gestión de los parques para el proceso de adaptación y mitigación del cambio global.The geoheritage and geodiversity of the national parks contribute, together with biodiversity, to make them protected natural areas that are unique in Spain, but also unique worldwide. Geoheritage is non-renewable and if it is lost or degraded it does so forever. Under the Global Change and Climate Change scenario, the geoheritage of the Canary national parks is highly vulnerable to the impacts caused by changes in temperature, flash floods, extreme storms, droughts, desertification, fires and sea level rise, fundamentally and to the impacts directly derived from human activity. These phenomena trigger the activation of geological processes that directly affect their conservation, in such a way that it is necessary to identify the geosites most threatened, to evaluate their impact and to establish the indicators at the scale of each national park for monitoring them. The knowledge of the current conservation status of geoheritage, its vulnerability and its direct threats will contribute to the management of the national parks for the process of adaptation and mitigation of Global Change.Depto. de Geodinámica, Estratigrafía y PaleontologíaDepto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEOrganismo Autónomo de Parques Nacionalespu

HTLV-1 infection in solid organ transplant donors and recipients in Spain

Background: HTLV-1 infection is a neglected disease, despite infecting 10–15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. Methods: All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. Results: A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. Conclusion: The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopath

Rapid subacute myelopathy following kidney transplantation from HTLV-1 donors: role of immunosuppresors and failure of antiretrovirals

Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor-recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Bounds on the density of sources of ultra-high energy cosmic rays from the Pierre Auger Observatory

We derive lower bounds on the density of sources of ultra-high energy cosmic rays from the lack of significant clustering in the arrival directions of the highest energy events detected at the Pierre Auger Observatory. The density of uniformly distributed sources of equal intrinsic intensity was found to be larger than similar to (0.06 – 5) x 10(-4) Mpc(-3) at 95% CL, depending on the magnitude of the magnetic defections. Similar bounds, in the range (0.2 – 7) x 10(-4) Mpc(-3), were obtained for sources following the local matter distribution.We are very grateful to the following agencies and organizations for financial support,: Comision Nacional de Energia Atomica, Fundacion Antorchas, Gobierno De La, Provincia de Ailendoza. Municipalidad de Malargile. INDM floldings and Valle Las Lenas, in gratitude for their continuing cooperation over land access. Argentina; the Australian Research Council; Conselho Nacional de Desenvolvimento Cientifico e 'Tecnologico (CNPq), Financiadora de Estudos e Projetos (FINEP), Fundacdo de Amparo a Pesquisa do Est ado de Rio de Janeiro (FAP HRJ), Fundacdo de Amparo Pesquisa do Estado de Sdo Paulo (FAPESP), Ministerio de Ciencia e Tecnologia (IVICT), Brazil; AVCR AVOZ10100502 and AVOZ10100522, GAAV KJB100100904, AISMT-CR LA08016, LG11044, 1VIEB111003, MSAI0021620859, LA08015, TACR TA01010517 and GA U.K. 119810, Czech Republic; Centre de Calcul I-N2P3/CNRS, Centre National de la -Recherche Scientifique ((1 NRS), Conseil Regional Ile-de-France, f)epartement, Physique Nuclealre et Corpusculaire (I N( Departement Sciences de l'Univers (SDU-INSU/CNRS), France; Bundesministerium fur Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DITG), Finanzministerium Baden-Wurttemberg, flelmholtz-Gemeinschaft Deutscher Forschungszentren Ministerium fur Wissenschaft und Forschung, Nordrhein-Westfalen, Ministerimn fur Wissenschaft, Forschung und Kunst, Baden-WUrttemberg, Germany; Istituto Nazion ale di Fisica Nucleare (INFN), Ministero dell'Istruzione, delhLniversita e della Ricerca (MIUR), Italy: Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico; Ministerie van Onden s Cultuur on NVetenschap Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO), Stichting voor Rmdamenteel Onderzoek der Materie (FOM), Netherlands; Ministry of Science and Higher Education, Grant Nos. N N202 200239 and N N202 207238, Poland; Portuguese national funds and FEDER funds within COMPETE - Programa Operacional Factores de Competitividade through Fundacao para a Ciencia e a Tecnologia, Portugal; Romanian Authority for Scientific Research ANCS, CNDI-UEFISETD1 partnership projects nr.20/2012 and nr.194/2012, project nr.1 /ASPERA2/20I2 ERA-NET and PN-IIRU-PD-2011-3-0145-17, Romania; Ministry for Higher Education, Science, and 'Technology, Slovenian Research Agency, Slovenia; Comunidad de Madrid, FEDER funds, Ministerio de Ciencia e Innovacion and Consolider-Ingenio 2010 (( PAN), X unta de Galicia Spain; Science and Technology Facilities Council, United kingdom; Department of Luergy, Contract Nos. DE-ACO2-07(11-111359, DE-FR02-04E1(41300, DE-FG02-99E1(41107, National Science Foundation, Grant No. 0450696, The Grainger Foundation U.S.A.; NAFOSTED, Vietnam; Marie Curie-IRSES/HPLANET, European Particle Physics Latin American Network, European Union 7th Frarneworlc Program. Grant No. IIRSES-2009-GA-246806; and UNESCO.Peer reviewe