Delimitation of geomorphological units by applying techniques of digital image processing and GIS : non-irrigated area: Lavalle, Mendoza

El objetivo de este trabajo consiste en la delimitación, a escala 1:100.000, de las principales unidades morfogenéticas y, a un mayor el nivel de detalle, de las geoformas dominantes del área no irrigada, departamento de Lavalle. Esto se realiza a partir del análisis geoespacial, que incluye el procesamiento digital de imágenes satelitales y la utilización de Sistemas de Información geográfica. En constante interacción con las técnicas de geoprocesamiento, se trabaja con información de campo obtenida en el área de estudio. A partir de la aplicación del método de relevamiento integral del paisaje se generan bases de datos temáticas y espaciales que permiten validar los resultados obtenidos en laboratorio para delimitar las formas del relieve. Se definieron las principales unidades morfoestructurales y las geoformas de acuerdo a su morfogénesis. Se toma como base el mapa geomorfológico de Mendoza (Abraham, 2000), ajustado espacialmente y ampliado temáticamente sobre las fuentes cartográficas y temáticas generadas por LaDyOT-IADIZA (2004-2009). El trabajo constituye una contribución metodológica a métodos de procesamiento telemétrico y digital a partir de trabajos de campo y análisis interpretativo de carácter analógico, en tanto los productos obtenidos permiten lograr información geoespacial estructurada en el ámbito de los SIG para diversos fines.The aim of this work was the definition, scale 1:100000, of the major morphogenetic units, and increased the level of detail, the dominant landforms of the area not irrigated Lavalle Department. This has been based on geospatial analysis, which includes the digital processing of satellite images and the use of Geographic Information Systems. In constant interaction with the application of geo-processing techniques, we worked with the information obtained from field analysis in the study area. Since the method of survey of the landscape were generated thematic databases and space to validate the laboratory results when defining the geoforms. Thus, the main units were defined morphostructural units and landforms according to their morphogenesis. It was derived from the geomorphologic map of the province of Mendoza (Abraham, 2000). The same was adjusted spatially and thematically expanded on the basis of cartographic and thematic sources generated LaDyOT-IADIZA (2004-2009). The work is a methodological contribution to processing methods and digital telemetry from fieldwork and interpretive analysis of a similar nature. While the products obtained can achieve structured geospatial information in the field of GIS for various purposes.Fil: Rubio, Cecilia. Instituto Argentino de Investigaciones de las Zonas Áridas Fil: Soria, Darío. Instituto Argentino de Investigaciones de las Zonas Áridas Fil: Salomón, Mario. Instituto Argentino de Investigaciones de las Zonas Áridas Fil: Abraham, Elena M.. Instituto Argentino de Investigaciones de las Zonas Áridas <IADIZA

Quantifying the motor efficiency via information theory

En este trabajo se propone un método para cuantificar la eficiencia motriz, basado en métricas específicas de la teoría de la información. Así, una medida de información es obtenida a partir de registros electromiográficos (EMG) y características cinemáticas de la actividad motora. Las señales de EMG fueron obtenidas del músculo deltoides medio durante contracciones dinámicas evocadas por elevaciones laterales (movimientos de abducción y aducción del brazo) en el plano escapular. Esta actividad motora fue realizada a diferentes velocidades y bajo diferentes condiciones de carga. La eficiencia de la actividad motora fue evaluada para cada situación. El método propuesto resultó adecuado para situaciones en el cual la actividad motora es realizada bajo condiciones no estacionarias (contracciones dinámicas).A method based on Information Theory for quantify the movement efficiency was proposed. The measurement of information provides a quantitative metric of motor efficiency. This measure is obtained from electromyographic (EMG) recordings and the kinematic of motor activity. Here, the EMG signals from middle right deltoid were recorded during dynamic contraction. These contractions were evoked by abduction-adduction arm movements at scapular plane. The arm movements were realized at different speeds and under different loading conditions. The efficiency of motor activity was then evaluated for each situation. The proposed method is suitable for situations in which motor activity is performed under non-stationary conditions (dynamic contractions).Fil: Soria, Verónica D.. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; ArgentinaFil: Navarro, Cecilia M.. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; ArgentinaFil: Pizá, Alvaro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; ArgentinaFil: Lucianna, Facundo Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Ruiz, Gabriel Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; ArgentinaFil: Farfan, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; Argentin

Magnetic domains in SrFe12O19/Co hard/soft bilayers

ESRF (The european Synchrotron) User Meeting 2022, 7 - 9 February, 2022 . -- online meeting . -- https://www.esrf.fr/fr/home/events/conferences/2022/user-meeting-2022.html .-- Youtube access: https://www.youtube.com/playlist?list=PLsWatK2_NAmyYnkC-bXhvT70wsYaTmojqThe nature of the magnetic coupling between a SrFe12O19 particle (hard phase) and a Co layer grown on top (soft phase) has been studied by means of photoemission electron microscopy (PEEM) and spatially-resolved x-ray absorption (XAS) and magnetic circular dichroism (XMCD) at CIRCE, ALBA synchrotron (Spain). Our study reveals the soft metallic overlayer presents an in-plane magnetization despite the strong out-of-plane magnetocrystalline anisotropy of the hard platelet. Thus, the two phases show completely uncorrelated magnetic domain patterns. Micromagnetic simulations seem to indicate the degree of exchange-coupling is low or null, although the conditions for rigid coupling are a priori well met

Fasciolosis Seroprevalence in Children from Fiambalá Valley, Tinogasta. Argentina

Fasciolosis is an alimentary zoonotic caused by Fasciola hepatica (unca or uncaca), a parasite that causes hepatobiliary disease with relative absence of gastrointestinal symptoms. Humans can get sick by eating plants or contaminated water. It is difficult to diagnose in the invasive stage becausethere are not eggs in feces. The need for count on diagnostic techniques with greater sensitivity and specificity is needed both for the clinic to determine endemic areas. Serological methods are useful in acute cases or as a screening test. Although fasciolosis is acquired at all ages, those most affected are children and lower of 19 ages groups have the highest rates of infection. The aim of this study was to determine the seroprevalence of fasciolosis in children and adolescents from Fiambalá Valley. There were collected serum samples from 77 children during the month of December 2009, in the town of Taton. They all agreed with their parents´written consent for evaluation. Thirty three serums were male and 44 female. Serum samples from children tested by ELISA for the detection of circulating IgG antibodies, revealed 44/77 (51,94 %) were positive. Twenty were females and 20 males. There was no significant difference by sex. The results show that the presence of fasciolosis should be considered as a disease of public health importance. Early detection should be a priority in control programs. The percentage of Fasciola hepatica infection found shows that Fiambalá valley is an endemic area for the different pathologies and requires strong educational intervention for prevention.La fasciolosis es una zoonosis alimentaria producida por Fasciola hepatica (unca o uncaca), parásito que causa patología hepatobiliar con relativa ausencia de síntomas gastrointestinales. Los seres humanos pueden enfermar al consumir vegetales o agua contaminada. Es de difícil diagnóstico en la fase invasiva porque no se encuentran huevos en heces. La necesidad de contar con técnicas de diagnóstico de mayor sensibilidad y especificidad es necesaria tanto para la clínica como para determinar zonas endémicas. Los métodos serológicos son útiles en casos agudos o como prueba de tamizaje. Aunque fasciolosis se adquiere en todas las edades, los más afectados son los niños y los grupos menores de 19 años presentan las mayores tasas de infección. El objetivo del presente estudio fue determinar la seroprevalencia de fasciolosis en niños y adolecentes del valle de Fiambalá. Se colectó 77 muestras de suero de niños, durante el mes de diciembre de 2009, en la localidad de Tatón. Todos accedieron con consentimiento escrito de sus padres para ser evaluados. Treinta y tres sueros fueron de sexo masculino y 44 del femenino. Las muestras de suero provenientes de niños analizados por la prueba de ELISA, para la detección de anticuerpos IgG circulantes, revelaron 44/ (51,94 %) positivos. Veinte fueron de sexo femenino y 20 varones. No se observó diferencia significativa por sexo. Los resultados permiten concluir que la presencia de fasciolosis debe considerarse como enfermedad de importancia en salud pública. La detección temprana debería ser una prioridad en los programas de control. El porcentaje de infección por Fasciola hepatica encontrado demuestra que el valle de Fiambalá es un área endémica para la patología estudiada y requiere fuerte intervención educativa para su prevención.Fil: Malandrini, Jorge Bruno. Universidad Nacional de Catamarca; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Carnevale, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Catamarca; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Soria, Claudia Cecilia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Universidad Nacional de Catamarca; ArgentinaFil: Velásquez, Jorge Néstor. Universidad Nacional de Catamarca; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Paladino, C. M.. Universidad Nacional de Catamarca; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentin

Fasciolosis Seroprevalence in Children from Fiambalá Valley, Tinogasta. Argentina

Fasciolosis is an alimentary zoonotic caused by Fasciola hepatica (unca or uncaca), a parasite that causes hepatobiliary disease with relative absence of gastrointestinal symptoms. Humans can get sick by eating plants or contaminated water. It is difficult to diagnose in the invasive stage becausethere are not eggs in feces. The need for count on diagnostic techniques with greater sensitivity and specificity is needed both for the clinic to determine endemic areas. Serological methods are useful in acute cases or as a screening test. Although fasciolosis is acquired at all ages, those most affected are children and lower of 19 ages groups have the highest rates of infection. The aim of this study was to determine the seroprevalence of fasciolosis in children and adolescents from Fiambalá Valley. There were collected serum samples from 77 children during the month of December 2009, in the town of Taton. They all agreed with their parents´written consent for evaluation. Thirty three serums were male and 44 female. Serum samples from children tested by ELISA for the detection of circulating IgG antibodies, revealed 44/77 (51,94 %) were positive. Twenty were females and 20 males. There was no significant difference by sex. The results show that the presence of fasciolosis should be considered as a disease of public health importance. Early detection should be a priority in control programs. The percentage of Fasciola hepatica infection found shows that Fiambalá valley is an endemic area for the different pathologies and requires strong educational intervention for prevention.La fasciolosis es una zoonosis alimentaria producida por Fasciola hepatica (unca o uncaca), parásito que causa patología hepatobiliar con relativa ausencia de síntomas gastrointestinales. Los seres humanos pueden enfermar al consumir vegetales o agua contaminada. Es de difícil diagnóstico en la fase invasiva porque no se encuentran huevos en heces. La necesidad de contar con técnicas de diagnóstico de mayor sensibilidad y especificidad es necesaria tanto para la clínica como para determinar zonas endémicas. Los métodos serológicos son útiles en casos agudos o como prueba de tamizaje. Aunque fasciolosis se adquiere en todas las edades, los más afectados son los niños y los grupos menores de 19 años presentan las mayores tasas de infección. El objetivo del presente estudio fue determinar la seroprevalencia de fasciolosis en niños y adolecentes del valle de Fiambalá. Se colectó 77 muestras de suero de niños, durante el mes de diciembre de 2009, en la localidad de Tatón. Todos accedieron con consentimiento escrito de sus padres para ser evaluados. Treinta y tres sueros fueron de sexo masculino y 44 del femenino. Las muestras de suero provenientes de niños analizados por la prueba de ELISA, para la detección de anticuerpos IgG circulantes, revelaron 44/ (51,94 %) positivos. Veinte fueron de sexo femenino y 20 varones. No se observó diferencia significativa por sexo. Los resultados permiten concluir que la presencia de fasciolosis debe considerarse como enfermedad de importancia en salud pública. La detección temprana debería ser una prioridad en los programas de control. El porcentaje de infección por Fasciola hepatica encontrado demuestra que el valle de Fiambalá es un área endémica para la patología estudiada y requiere fuerte intervención educativa para su prevención.Fil: Malandrini, Jorge Bruno. Universidad Nacional de Catamarca; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Carnevale, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Catamarca; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Soria, Claudia Cecilia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Universidad Nacional de Catamarca; ArgentinaFil: Velásquez, Jorge Néstor. Universidad Nacional de Catamarca; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Paladino, C. M.. Universidad Nacional de Catamarca; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentin

Real space observation of the magnetic coupling between a Co film and a barium hexaferrite film

RIVA ONLINE 2021 – IBERIAN VACUUM ONLINE MEETING. The Iberian Vacuum Conference, (Reunión Ibérica de Vacío, RIVA) is a joint meeting of the Portuguese Vacuum Society (SOPORVAC) and the Spanish Vacuum Society (ASEVA), 2021 RIVA will take place ON-LINE from 4-6th October 2021. .-https://aseva.es/conferences/riva-online/Barium ferrite (BaFe12O19, BFO) is a hexagonal ferrite with applications as permanent magnet in many different devices due to its high magnetocrystalline anisotropy, high coercive field and low cost. However, the moderate saturation magnetization of BFO means that the energy product is orders of magnitude smaller than the one that rare-earth-based magnetic materials offer. To overcome this limitation, a commonly proposed strategy to enhance the energy product is exchange-coupling the magnetically hard component (BFO) with a soft phase in order to improve the combined remanent magnetization without a high loss in coercivity. Nonetheless, the results obtained in other hard/soft systems (SFO/Co bilayers) have pointed out the difficulty to take advantage of this rigid coupling magnetic regime1. In this research, we focus on two steps to investigate the Co/BFO coupling in a bilayer system: first, we sought to obtain BFO films with an in- plane magnetic easy axis to avoid shape anisotropy competition, and second, we deposit Co on top of such a BFO film while monitoring both the BFO and Co magnetic domains

Insights onto the magnetic coupling at hexaferrite-based hard/soft bilayer systems

IBERTRIVA 2019 X Iberian Conference on Tribology – IBERTRIB, XI Iberian Vacuum Conference - RIVA, Seville, Spain,June 26-28Magnets are used in a variety of applications, such as generators, magnetic recording media, components in RF and microwave devices. However, many of these magnets contain s rare earths, critical elements whose extraction is environmentally harmful and that present price volatility risks. Their replacement by cheaper and more environmentally friendly materials is therefore sought. In our case, we have focused on magnetically hard strontium hexaferrite (SrFe 12O19, SFO) as the base for alternative permanent magnets (Figure 1a). The atomic arrangement of this ferrite results in a high magnetocrystalline anisotropy and a coercive field, however, its magnetization is moderate (1). It is well known that the coupling between a magnetically hard and soft material improved magnetization while avoiding a high cost in coercitivity loss (2). However, results have been disappointing so far as structural and geometrical limitations make it extremely challenging to fabricate. In this work, we aim at further understanding the magnetic coupling at hard -soft interfaces involving ferrites, for which we have deposited soft iron and cobalt metals on top of SrFe12O19 thin films with controlled easy-axis of magnetization. SFO thin films have been obtained by RF magnetron sputtering at 260W followed by a subsequent annealing in air of 850ºC. Their structure and composition was characterized by Raman spectroscospy (Figure 1b), Mössbauer spectroscopy, X-ray photoemission spectroscopy and low-energy electron microscopy (LEEM). We have grown the magnetically soft layer by molecular-beam epitaxy and we have analyzed the resulting bilayer system through photoemission electron microscopy, LEEM and vibrating-sample magnetometry. References [1] R.C. Pullar, Hexagonal ferrites: a review of the synthesis, properties and applications of hexaferrite ceramics, Progress in Materials Science 57 (2012), pp 1191¿1334. [2] Eric E. Fullerton, J. S. Jiang, M. Grimsditch, C. H. Sowers, and S. D. Bader, Exchange-spring behavior in epitaxial hard/soft magnetic bilayers, Phys. Rev. B 58 (1998) 1219

Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

Snakebite envenoming is a global neglected disease with an incidence of up to 2.7 million new cases every year. Although antivenoms are so-far the most effective treatment to reverse the acute systemic effects induced by snakebite envenoming, they have a limited therapeutic potential, being unable to completely neutralize the local venom effects. Local damage, such as dermonecrosis and myonecrosis, can lead to permanent sequelae with physical, social, and psychological implications. The strong inflammatory process induced by snake venoms is associated with poor tissue regeneration, in particular the lack of or reduced skeletal muscle regeneration. Mesenchymal stromal cells (MSCs)-based therapies have shown both anti-inflammatory and pro-regenerative properties. We postulate that using allogeneic MSCs or their cell-free products can induce skeletal muscle regeneration in snakebite victims, improving all the three steps of the skeletal muscle regeneration process, mainly by anti-inflammatory activity, paracrine effects, neovascularization induction, and inhibition of tissue damage, instrumental for microenvironment remodeling and regeneration. Since snakebite envenoming occurs mainly in areas with poor healthcare, we enlist the principles and potential of MSCs-based therapies and discuss regulatory issues, good manufacturing practices, transportation, storage, and related-procedures that could allow the administration of these therapies, looking forward to a safe and cost-effective treatment for a so far unsolved and neglected health problem.The authors are supported by the University Pablo de Olavide (Sevilla), the University Miguel Hernández (Elche, Alicante), National University Toribio Rodriguez de Mendoza (Chachapoyas, Peru) Grants: Contrato N° 09-2019-FONDECYT-BM-INC.INV to JRT, JDRF 2-SRA-2019-837-S-B and AVI-GVA COVID-19-68 to BS, Fundación Andaluza de I+D and Al-Andalus Biopharma Project (FAID-2018-1). The authors CC-O, CG-D, and TCSA were supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq) (Process: 406163/2018-9), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil - CAPES (Program COFECUB Process: 88881.191812/2018-01) and by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG)

Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease

Graft versus host disease (GvHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). Here we report studies of a patient with chronic GvHD (cGvHD) carrying persistent CD4(+) T cell clonal expansion harboring somatic mTOR, NFKB2, and TLR2 mutations. In the screening cohort (n=134), we detect the mTOR P2229R kinase domain mutation in two additional cGvHD patients, but not in healthy or HSCT patients without cGvHD. Functional analyses of the mTOR mutation indicate a gain-of-function alteration and activation of both mTORC1 and mTORC2 signaling pathways, leading to increased cell proliferation and decreased apoptosis. Single-cell RNA sequencing and real-time impedance measurements support increased cytotoxicity of mutated CD4(+) T cells. High throughput drug-sensitivity testing suggests that mutations induce resistance to mTOR inhibitors, but increase sensitivity for HSP90 inhibitors. Our findings imply that somatic mutations may contribute to aberrant T cell proliferations and persistent immune activation in cGvHD, thereby paving the way for targeted therapies. Chronic graft versus host disease (cGvHD) is a major cause of morbidity and mortality in allogeneic bone marrow transplantation. Here the authors identify a recurrent activating mTOR mutation in expanded donor T-cell clones of 3 cGvHD patients, which suggests somatic mutations may contribute to GvHD pathogenesis and opens avenues to targeted therapies.Peer reviewe

European youth care sites serve different populations of adolescents with cannabis use disorder. Baseline and referral data from the INCANT trial

Background: MDFT (Multidimensional Family Therapy) is a family based outpatient treatment programme for adolescent problem behaviour. MDFT has been found effective in the USA in adolescent samples differing in severity and treatment delivery settings. On request of five governments (Belgium, France, Germany, the Netherlands, and Switzerland), MDFT has now been tested in the joint INCANT trial (International Cannabis Need of Treatment) for applicability in Western Europe. In each of the five countries, study participants were recruited from the local population of youth seeking or guided to treatment for, among other things, cannabis use disorder. There is little information in the literature if these populations are comparable between sites/countries or not. Therefore, we examined if the study samples enrolled in the five countries differed in baseline characteristics regarding demographics, clinical profile, and treatment delivery setting.Methods: INCANT was a multicentre phase III(b) randomized controlled trial with an open-label, parallel group design. It compared MDFT with treatment as usual (TAU) at and across sites in Berlin, Brussels, Geneva, The Hague and Paris.Participants of INCANT were adolescents of either sex, from 13 through 18 years of age, with a cannabis use disorder (dependence or abuse), and at least one parent willing to take part in the treatment. In total, 450 cases/families were randomized (concealed) into INCANT.Results: We collected data about adolescent and family demographics (age, gender, family composition, school, work, friends, and leisure time). In addition, we gathered data about problem behaviour (substance use, alcohol and cannabis use disorders, delinquency, psychiatric co-morbidity).There were no major differences on any of these measures between the treatment conditions (MDFT and TAU) for any of the sites. However, there were cross-site differences on many variables. Most of these could be explained by variations in treatment culture, as reflected by referral policy, i.e., participants' referral source. We distinguished 'self-determined' referral (common in Brussels and Paris) and referral with some authority-related 'external' coercion (common in Geneva and The Hague). The two referral types were more equally divided in Berlin. Many cross-site baseline differences disappeared when we took referral source into account, but not all.Conclusions: A multisite trial has the advantage of being efficient, but it also carries risks, the most important one being lack of equivalence between local study populations. Our site populations differed in many respects. This is not a problem for analyses and interpretations if the differences somehow can be accounted for. To a major extent, this appeared possible in INCANT. The most important factor underlying the cross-site variations in baseline characteristics was referral source. Correcting for referral source made most differences disappear. Therefore, we will use referral source as a covariate accounting for site differences in future INCANT outcome analyses