Hypoxic glioblastoma-cell-derived extracellular vesicles impair cGAS-STING activity in macrophages.

BACKGROUND: Solid tumors such as glioblastoma (GBM) exhibit hypoxic zones that are associated with poor prognosis and immunosuppression through multiple cell intrinsic mechanisms. However, release of extracellular vesicles (EVs) has the potential to transmit molecular cargos between cells. If hypoxic cancer cells use EVs to suppress functions of macrophages under adequate oxygenation, this could be an important underlying mechanism contributing to the immunosuppressive and immunologically cold tumor microenvironment of tumors such as GBM. METHODS: EVs were isolated by differential ultracentrifugation from GBM cell culture supernatant. EVs were thoroughly characterized by transmission and cryo-electron microscopy, nanoparticle tracking analysis (NTA), and EV marker expression by Western blot and fluorescent NTA. EV uptake by macrophage cells was observed using confocal microscopy. The transfer of miR-25/93 as an EV cargo to macrophages was confirmed by miRNA real-time qPCR. The impact of miR-25/93 on the polarization of recipient macrophages was shown by transcriptional analysis, cytokine secretion and functional assays using co-cultured T cells. RESULTS: We show that indirect effects of hypoxia can have immunosuppressive consequences through an EV and microRNA dependent mechanism active in both murine and human tumor and immune cells. Hypoxia enhanced EV release from GBM cells and upregulated expression of miR-25/93 both in cells and in EV cargos. Hypoxic GBM-derived EVs were taken up by macrophages and the miR-25/93 cargo was transferred, leading to impaired cGAS-STING pathway activation revealed by reduced type I IFN expression and secretion by macrophages. The EV-treated macrophages downregulated expression of M1 polarization-associated genes Cxcl9, Cxcl10 and Il12b, and had reduced capacity to attract activated T cells and to reactivate them to release IFN-γ, key components of an efficacious anti-tumor immune response. CONCLUSIONS: Our findings suggest a mechanism by which immunosuppressive consequences of hypoxia mediated via miRNA-25/93 can be exported from hypoxic GBM cells to normoxic macrophages via EVs, thereby contributing to more widespread T-cell mediated immunosuppression in the tumor microenvironment.

Radio-chemotherapy of glioblastoma cells promotes phagocytosis by macrophages in vitro.

BACKGROUND AND PURPOSE: Immunotherapy is actively explored in glioblastoma (GBM) to improve patient prognosis. Tumor-associated macrophages (TAMs) are abundant in GBM and harnessing their function for anti-tumor immunity is of interest. They are plastic cells that are influenced by the tumor microenvironment, by radio-chemotherapy and by their own phagocytic activity. Indeed, the engulfment of necrotic cells promotes pro-inflammatory (and anti-tumoral) functions while the engulfment of apoptotic cells promotes anti-inflammatory (and pro-tumoral) functions through efferocytosis. MATERIALS AND METHODS: To model the effect of radio-chemotherapy on the GBM microenvironment, we exposed human macrophages to supernatant of treated GBM cells in vitro. Macrophages were derived from human monocytes and GBM cells from patient-resected tumors. GBM cells were exposed to therapeutically relevant doses of irradiation and chemotherapy. Apoptosis and phagocytic activity were assessed by flow cytometry. RESULTS: The phagocytic activity of macrophages was increased, and it was correlated with the proportion of apoptotic GBM cells producing the supernatant. Whether uptake of apoptotic tumor cells could occur would depend upon the expression of efferocytosis-associated receptors. Indeed, we showed that efferocytosis-associated receptors, such as AXL, were upregulated. CONCLUSIONS AND PERSPECTIVES: We showed that macrophage phagocytic activity increased when exposed to supernatant from GBM cells treated by radio-chemotherapy. However, as efferocytosis-associated receptors were up-regulated, this effect could be deleterious for the anti-GBM immune response. We speculate that by inducing GBM cell apoptosis in parallel to an increase in efferocytosis receptor expression, the impact of radio-chemotherapy on phagocytic activity could promote anti-inflammatory and pro-tumoral TAM functions.

Co-Formulation of Recombinant Porcine IL-18 Enhances the Onset of Immune Response in a New Lawsonia intracellularis Vaccine.

Pig is one of the most consumed meats worldwide. One of the main conditions for pig production is Porcine Enteropathy caused by Lawsonia intracellularis. Among the effects of this disease is chronic mild diarrhea, which affects the weight gain of pigs, generating economic losses. Vaccines available to prevent this condition do not have the desired effect, but this limitation can be overcome using adjuvants. Pro-inflammatory cytokines, such as interleukin 18 (IL-18), can improve an immune response, reducing the immune window of protection. In this study, recombinant porcine IL-18 was produced and expressed in Escherichia coli and Pichia pastoris. The protein's biological activity was assessed in vitro and in vivo, and we determined that the P. pastoris protein had better immunostimulatory activity. A vaccine candidate against L. intracellularis, formulated with and without IL-18, was used to determine the pigs' cellular and humoral immune responses. Animals injected with the candidate vaccine co-formulated with IL-18 showed a significant increase of Th1 immune response markers and an earlier increase of antibodies than those vaccinated without the cytokine. This suggests that IL-18 acts as an immunostimulant and vaccine adjuvant to boost the immune response against the antigens, reducing the therapeutic window of recombinant protein-based vaccines.

Relación entre actividad física, rendimiento académico y funciones ejecutivas en adolescentes: una revisión sistemática / Relationship between physical activity, academic performance and executive functions in adolescents: a systematic review / Relação entre atividade física, Rendimento acadêmico e funções executivas em adolescentes: uma revisão sistemática

El objetivo de este estudió fue analizar la producción científica actual sobre el nivel de actividad física, rendimiento académico y funciones ejecutivas, con el fin de relacionar los beneficios del ejercicio con los procesos cognitivos de escolares. Metodología: Para la revisión y selección de artículos, se siguió la metodología de revisión sistemática basada en las declaraciones internacionales PRISMA. Las principales bases de datos utilizadas son; Dimensions, LILAC, PubMed, Scielo, Scopus y Dialnet. Búsqueda de artículos de intervención y de revisión publicados entre 2013 y 2020, con un rango etario de 10 a 18 años y escritos en idioma español. Los resultados indican que los estudios centran sus objetivos en analizar y comparar las relaciones entre las variables AF, RE y FE. Se concluye que existe una influencia positiva de la actividad física sobre las variables de rendimiento académico y funciones ejecutivas, lo que se traduce principalmente en una mejora en matemáticas y/o lectura, en la memoria y la atención.

The objective of this study was to analyze the current scientific production on the level of physical activity, academic performance, and executive functions, in order to relate the benefits of exercise to the cognitive processes of schoolchildren. Methodology: For the review and selection of articles, we followed the systematic review methodology based on the PRISMA international declarations. The main databases used are: Dimensions, LILAC, PubMed, Scielo, Scopus, and Dialnet. The search focused on intervention and review articles published between 2013 and 2020, with an age range of 10 to 18 years old and written in Spanish. The results indicate that the studies focus their objectives on analyzing and comparing the relationships between the FA, AP, and EF variables. It is concluded that there is a positive influence of physical activity on the variables of academic performance and executive functions, which mainly translates into an improvement in mathematics and/or reading, as well as in memory and attention.

O objetivo deste estudo foi analisar a produção científica atual sobre o nível de atividade física, rendimento acadêmico e funções executivas, a fim de relacionar os benefícios do exercício físico com os processos cognitivos de escolares. Metodologia: para a revisão e seleção dos artigos, seguiu-se a metodologia de revisão sistemática baseada nas declarações internacionais PRISMA. As principais bases de dados utilizadas são: Dimensões, LILAC, PubMed, Scielo, Scopus e Dialnet. Pesquisa de artigos de intervenção e revisão publicados entre 2013 e 2020, com faixa etária de 10 a 18 anos e escritos em espanhol. Os resultados indicam que os estudos focam seus objetivos em analisar e comparar as relações entre as variáveis AF, RE e FE. Conclui-se que existe uma influência positiva da atividade física nas variáveis de desempenho acadêmico e funções executivas, o que se traduz principalmente em melhora em matemática e/ou leitura, em memória e atenção.

Treating ICB-resistant glioma with anti-CD40 and mitotic spindle checkpoint controller BAL101553 (lisavanbulin).

Glioblastoma is a highly malignant brain tumor with no curative treatment options, and immune checkpoint blockade has not yet shown major impact. We hypothesized that drugs targeting mitosis might affect the tumor microenvironment and sensitize cancer cells to immunotherapy. We used 2 glioblastoma mouse models with different immunogenicity profiles, GL261 and SB28, to test the efficacy of antineoplastic and immunotherapy combinations. The spindle assembly checkpoint activator BAL101553 (lisavanbulin), agonistic anti-CD40 antibody, and double immune checkpoint blockade (anti-programmed cell death 1 and anti-cytotoxic T lymphocyte-associated protein 4; anti-PD-1 and anti-CTLA-4) were evaluated individually or in combination for treating orthotopic GL261 and SB28 tumors. Genomic and immunological analyses were used to predict and interpret therapy responsiveness. BAL101553 monotherapy increased survival in immune checkpoint blockade-resistant SB28 glioblastoma tumors and synergized with anti-CD40 antibody, in a T cell-independent manner. In contrast, the more immunogenic and highly mutated GL261 model responded best to anti-PD-1 and anti-CTLA-4 therapy and more modestly to BAL101553 and anti-CD40 combination. Our results show that BAL101553 is a promising therapeutic agent for glioblastoma and could synergize with innate immune stimulation. Overall, these data strongly support immune profiling of glioblastoma patients and preclinical testing of combination therapies with appropriate models for particular patient groups.

Evaluation of the Pediatric Neuro-Oncology Resources Available in Chile.

PURPOSE: Pediatric neuro-oncology resources are mostly unknown in Chile. We report the human and material resources available in Chilean hospitals providing pediatric neuro-oncology services. METHODS: A cross-sectional survey was distributed to 17 hospitals providing pediatric neuro-oncology services (Programa Infantil Nacional de Drogas Antineoplásicas [PINDA] hospitals, 11; private, 6). RESULTS: Response rate was 71% (PINDA, 8; private, 4). Pediatric neuro-oncology services were mainly provided within general hospitals (67%). Registries for pediatric CNS tumors and chemotherapy-related toxicities were available in 100% and 67% of hospitals, respectively. CNS tumors were treated by pediatric oncologists in 92% of hospitals; none were formally trained in neuro-oncology. The most used treatment protocols were the national PINDA protocols. All WHO essential medicines for childhood cancer were available in more than 80% of the hospitals except for gemcitabine, oxaliplatin, paclitaxel, and procarbazine. The median number of pediatric neurosurgeons per hospital was two (range, 2-6). General neuroradiologists were available in 83% of the centers. Pathology specimens were sent to neuropathologists (58%), adult pathologists (25%), and pediatric pathologists (17%). Intensity-modulated radiotherapy, conformal radiotherapy, and cobalt radiotherapy were used by 67%, 58%, and 42% of hospitals, respectively. Only one private hospital performed autologous hematopoietic cell transplant for children with CNS tumors. CONCLUSION: A wide range of up-to-date treatment modalities are available for children with CNS tumors. Our survey highlights future directions to improve the pediatric neuro-oncology services available in Chile such as the expansion of multidisciplinary clinics, palliative care services, long-term cancer survivorship programs, dedicated clinical research support teams, establishing standardized mechanism for sending pathologic specimen for second opinion to international specialized centers, and establishing specialized neuro-oncology training program.

A Heterologous Viral Protein Scaffold for Chimeric Antigen Design: An Example PCV2 Virus Vaccine Candidate.

Recombinant vaccines have low-cost manufacturing, regulatory requirements, and reduced side effects compared to attenuated or inactivated vaccines. In the porcine industry, post-weaning multisystemic disease syndrome generates economic losses, characterized by progressive weight loss and weakness in piglets, and it is caused by porcine circovirus type 2 (PCV2). We designed a chimeric antigen (Qm1) to assemble the main exposed epitopes of the Cap-PCV2 protein on the capsid protein of the tobacco necrosis virus (TNV). This design was based on the Cap-N-terminal of an isolated PCV2 virus obtained in Chile. The virus was characterized, and the sequence was clustered within the PCV2 genotype b clade. This chimeric protein was expressed as inclusion bodies in both monomeric and multimeric forms, suggesting a high-molecular-weight aggregate formation. Pigs immunized with Qm1 elicited a strong and specific antibody response, which reduced the viral loads after the PCV2 challenge. In conclusion, the implemented design allowed for the generation of an effective vaccine candidate. Our proposal could be used to express the domains or fragments of antigenic proteins, whose structural complexity does not allow for low-cost production in Escherichia coli. Hence, other antigen domains could be integrated into the TNV backbone for suitable antigenicity and immunogenicity. This work represents new biotechnological strategies, with a reduction in the costs associated with vaccine development.

Defining Global Benchmarks in Bariatric Surgery: A Retrospective Multicenter Analysis of Minimally Invasive Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

OBJECTIVE: To define "best possible" outcomes for bariatric surgery (BS)(Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]). BACKGROUND: Reference values for optimal surgical outcomes in well-defined low-risk bariatric patients have not been established so far. Consequently, outcome comparison across centers and over time is impeded by heterogeneity in case-mix. METHODS: Out of 39,424 elective BS performed in 19 high-volume academic centers from 3 continents between June 2012 and May 2017, we identified 4120 RYGB and 1457 SG low-risk cases defined by absence of previous abdominal surgery, concomitant procedures, diabetes mellitus, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, anticoagulation, BMI>50 kg/m and age>65 years. We chose clinically relevant endpoints covering the intra- and postoperative course. Complications were graded by severity using the comprehensive complication index. Benchmark values were defined as the 75th percentile of the participating centers' median values for respective quality indicators. RESULTS: Patients were mainly females (78%), aged 38±11 years, with a baseline BMI 40.8 ±â€Š5.8 kg/m. Over 90 days, 7.2% of RYGB and 6.2% of SG patients presented at least 1 complication and no patients died (mortality in nonbenchmark cases: 0.06%). The most frequent reasons for readmission after 90-days following both procedures were symptomatic cholelithiasis and abdominal pain of unknown origin. Benchmark values for both RYGB and SG at 90-days postoperatively were 5.5% Clavien-Dindo grade ≥IIIa complication rate, 5.5% readmission rate, and comprehensive complication index ≤33.73 in the subgroup of patients presenting at least 1 grade ≥II complication. CONCLUSION: Benchmark cutoffs targeting perioperative outcomes in BS offer a new tool in surgical quality-metrics and may be implemented in quality-improvement cycle.ClinicalTrials.gov Identifier NCT03440138.

Dos décadas de Acta Colombiana de Psicología: un análisis bibliométrico / Duas décadas de Acta Colombiana de Psicología: uma análise bibliométrica / Two decades of Acta Colombiana de Psicología: a bibliometric analysis

Resumen El objetivo del presente estudio fue realizar un análisis bibliométrico de la revista Acta Colombiana de Psicología, debido a sus dos décadas de trabajo ininterrumpido (1998-2017). Inicialmente, se describen elementos históricos en la trayectoria de la revista y se releva su evolución cronológica a partir de una base de datos que consideró 388 artículos científicos en su muestra final; posteriormente, se realizaron los análisis de los índices de productividad (Lotka) y de las temáticas y metodologías utilizadas. Asimismo, se desarrolló un análisis de los indicadores de colaboración y de las relaciones entre los autores con respecto a los países firmantes. En los resultados se destaca la gran cantidad de trabajos provenientes de instituciones mexicanas, se visualiza un alza sostenida en la colaboración -lo que se evidencia en los índices de Lawani y Subramanyam-, y se encuentra que la mayor cantidad de trabajos se enfocó en las áreas de psicología clínica y de la salud. El análisis realizado permite exhibir lo realizado por la revista a lo largo de dos décadas de trabajo científico en las que se aportó de manera fundamental al desarrollo de la psicología en Hispanoamérica.

Resumo O objetivo do presente estudo foi realizar uma análise bibliométrica da revista Acta Colombiana de Psicología, devido a suas duas décadas de trabalho ininterrupto (1998-2017). Inicialmente, descrevem-se elementos históricos na trajetória da revista e revela-se sua evolução cronológica a partir de uma base de dados que considerou 388 artigos científicos em sua amostra final. Posteriormente, foram realizadas as análises dos índices de produtividade (Lotka) e das temáticas e metodologias utilizadas. Além disso, foi desenvolvida uma análise dos indicadores de colaboração e das relações entre os autores com respeito aos países signatários. Nos resultados, destaca-se a grande quantidade de trabalhos provenientes de instituições mexicanas, visualiza-se uma alta prolongada na colaboração - o que se evidencia nos índices de Lawani e Subramanyam -, e nota-se que a maior quantidade de trabalhos concentrou-se nas áreas de psicologia clínica e da saúde. A análise realizada permite exibir o feito da revista ao longo de duas décadas de trabalho científico nas quais colaborou de maneira fundamental para o desenvolvimento da psicologia na América espanhola.

Abstract The aim of the present study was to conduct a bibliometric analysis of the journal Acta Colombiana de Psicología, by virtue of its two decades of uninterrupted work (1998-2017). Initially, historical elements are described in the trajectory of the journal and its chronological evolution is revealed from a database that in its final sample took into account 388 scientific articles. Subsequently, the appraisal of the productivity indices (Lotka) as well as of the topics and methodologies used was carried out. Likewise, an appraisal of the collaboration indicators and the relationships between the authors with respect to the signatory countries was performed. The results highlight the large number of papers from Mexican institutions, a sustained increase in collaboration is visualized -which is evident in the Lawani and Subramanyam indices-, and it is found that the largest amount of papers focused on the areas of clinical and health psychology. The analysis undertaken allows showing what the journal has achieved throughout two decades of scientific work during which it contributed fundamentally to the development of psychology in Latin America.

Results of Therapy for Wilms Tumor and Other Malignant Kidney Tumors: A Report From the Chilean Pediatric National Cancer Program (PINDA).

OBJECTIVE: The aim of this study was to analyze the survival of children with Wilms tumor and other malignant renal tumors treated with the TWPINDA-99 protocol. MATERIALS AND METHODS: Between January 1999 and December 2013, 226 patients were registered on this trial, based on National Wilms Tumor Study-5. Patient characteristics and survival were evaluated. RESULTS: Two hundred seven patients were diagnosed with Wilms tumor, which represented 91.6% of renal tumors. The male to female ratio was 0.7:1. The median age at diagnosis was 3.3 years. Stage III was the most frequent (39.2%). Metastatic disease was present in 16.7% of the cases. Synchronous bilateral disease was observed in 9.3% of the cases. Favorable histology was diagnosed in 93.6% and anaplastic histology in 6.4% of the patients. Median follow-up was 7.5 years. Ten-year event-free survival and overall survival (OS) for assessable patients with Wilms tumor (n=192) were 82.0% and 89.9%, respectively. OS for patients with stage I was 100% (n=36), stage II: 97.1% (n=35), stage III: 88.6% (n=71), stage IV: 77.9% (n=32), and stage V: 80.8% (n=18). OS for favorable histology (n=180) and anaplastic histology tumors (n=12) were 91.0% and 72.9%, respectively. Other malignant renal tumors had a poorer survival. CONCLUSION: Prognosis for patients with Wilms tumor treated on TWPINDA-99 seems to be better than previous national trials and is similar to developed countries.

Using the standard deviation of a region of interest in an image to estimate camera to emitter distance.

In this study, a camera to infrared diode (IRED) distance estimation problem was analyzed. The main objective was to define an alternative to measures depth only using the information extracted from pixel grey levels of the IRED image to estimate the distance between the camera and the IRED. In this paper, the standard deviation of the pixel grey level in the region of interest containing the IRED image is proposed as an empirical parameter to define a model for estimating camera to emitter distance. This model includes the camera exposure time, IRED radiant intensity and the distance between the camera and the IRED. An expression for the standard deviation model related to these magnitudes was also derived and calibrated using different images taken under different conditions. From this analysis, we determined the optimum parameters to ensure the best accuracy provided by this alternative. Once the model calibration had been carried out, a differential method to estimate the distance between the camera and the IRED was defined and applied, considering that the camera was aligned with the IRED. The results indicate that this method represents a useful alternative for determining the depth information.

Tratamiento del Pectus excavatum con cirugía minimamente invasiva con la técnica de Donald Nuss / Treatment of pectus excavatum with minimally invasive surgery by Donald Nuss technique

El Pectus excavatum, es una malformación congénita de la pared anterior del tórax, caracterizada por una depresión del esternón. Objetivo: Evaluar los resultados del tratamiento quirúrgico en pacientes con pectus excavatum, utilizando la técnica de Nuss. Material y métodos: Diez pacientes con Pectus excavatum, de 6 a 22 años, operados, fueron incluidos. El seguimiento fue de 2 a 14 meses. Resultados: La edad promedio fue 11,5 años, ocho fueron varones, seis tuvieron pectus excavatum simétrico, el Índice de Haller promedio fue 5,1. La indicación de cirugía fue sintomatología broncopulmonar en 4, cuatro cardiológica, uno psicológico y otro recidiva de pectus Post-Ravitch. En todos los pacientes se implantó una barra metálica con dos estabilizadores, el tiempo operatorio fue entre 2 y 4 horas y la estancia hospitalaria, 7 días. Tres pacientes presentaron complicaciones postoperatorias: neumotórax en dos y en uno fijación inadecuada; en el seguimiento los pacientes no fueron asintomáticas y todos mostraron satisfacción con el tratamiento. Conclusiones: La técnica de Donald Nuss es un procedimiento que corrige el Pectus Excavatum, reduce el tiempo operatorio y estancia hospitalaria, con presentación de complicaciones menores y resultados clínico-psicológicos satisfactorios.(Rev Med Hered 2011;22:108-114).

Pectus excavatum is a congenital malformation of anterior wall of the chest, characterized by a depression of the sternum. Objective: To evaluate the results of surgical treatment in patients with pectus excavatum, using the technique of Nuss. Material and methods: 10 patients with Pectus excavatum, from 6 to 22 years, were included.Post surgical was follow-up 2 to 14 months. Results: Mean age was 11.5 years, eight were male, six had symmetrical pectus excavatum, the Haller index average 5.1. The indication for surgery was bronchopulmonary, symptons in four, four cardiac, one psychological and another recurrence of pectus Post-Ravitch. All patients received a metal bar with two stabilizers, operative time was between 2 y 4 hours and hospital stay was seven days. Three patients had postoperative complications: pneumothorax in two and one with inadequate fixation bar; in follow-up patients were asymptomatic and all show satisfaction with treatment. Conclusions: The Donald Nuss technique is a procedure to correct Pectus excavatum, reduces operative time and hospital stay, with presentation of minor complications and clínics and psicológics results.(Rev Med Hered 2011;22:108-114).

Fitoexperimentación pura con refrescos / Fitoexperimentación pure refreshment

La Fitoexperimentación pura es un mecanismo adecuado para conocer el efecto biológico que tiene uma substancia sobre una planta, la importancia de esto es que conociendo los síntomas que genera la sustancia en dosis cuantificable es posible la aplicación de esa sustancia para corregir los síntomas causados por la misma.

Fitoexperimentación pura con refrescos / Fitoexperimentación pure refreshment

La Fitoexperimentación pura es un mecanismo adecuado para conocer el efecto biológico que tiene uma substancia sobre una planta, la importancia de esto es que conociendo los síntomas que genera la sustancia en dosis cuantificable es posible la aplicación de esa sustancia para corregir los síntomas causados por la misma.

Efecto biológico de dinamizaciones homeopáticas de Barbasco (Discorea villosa) en Trigo (triticum aestivum) / Biological effect of homeopathic dynamic Barbasco (Discorea villosa) in wheat (Triticum aestivum)

Los processos de contaminación que afectan a la sociedad están generando múltiples problemas, sobre todo de salud, que están relacionados con el consumo de alimentos. La agudización de las enfermedades crónicas degenerativas hace que sea una necessidade el fortalecimento de alternativas que tiendan a preservar la vida humana.

Efecto biológico de dinamizaciones homeopáticas de Barbasco (Discorea villosa) en Trigo (triticum aestivum) / Biological effect of homeopathic dynamic Barbasco (Discorea villosa) in wheat (Triticum aestivum)

Los processos de contaminación que afectan a la sociedad están generando múltiples problemas, sobre todo de salud, que están relacionados con el consumo de alimentos. La agudización de las enfermedades crónicas degenerativas hace que sea una necessidade el fortalecimento de alternativas que tiendan a preservar la vida humana.

Design of aquifer remediation systems: (1) describing hydraulic structure and NAPL architecture using tracers.

Aquifer heterogeneity (structure) and NAPL distribution (architecture) are described based on tracer data. An inverse modelling approach that estimates the hydraulic structure and NAPL architecture based on a Lagrangian stochastic model where the hydraulic structure is described by one or more populations of lognormally distributed travel times and the NAPL architecture is selected from eight possible assumed distributions. Optimization of the model parameters for each tested realization is based on the minimization of the sum of the square residuals between the log of measured tracer data and model predictions for the same temporal observation. For a given NAPL architecture the error is reduced with each added population. Model selection was based on a fitness which penalized models for increasing complexity. The technique is demonstrated under a range of hydrologic and contaminant settings using data from three small field-scale tracer tests: the first implementation at an LNAPL site using a line-drive flow pattern, the second at a DNAPL site with an inverted five-spot flow pattern, and the third at the same DNAPL site using a vertical circulation flow pattern. The Lagrangian model was capable of accurately duplicating experimentally derived tracer breakthrough curves, with a correlation coefficient of 0.97 or better. Furthermore, the model estimate of the NAPL volume is similar to the estimates based on moment analysis of field data.