Contributions from functional neuroimaging studies to the comprehension of traumatic child experiences: preliminary findings / Aportes de los estudios de neuroimagen funcional a la comprensión del trauma infantil: estudio preliminar

Abstract This study aimed to describe the cerebral activation patterns using fMRI (Functional Magnetic Resonance Imaging) technology in a sample of 15 children with Posttraumatic Stress Disorder (PTSD) and 7 with no PTSD. The study used a Quasi-experimental methodology where two experimental tasks were applied: an emotional face task and a version of an emotional Stroop task. The results point out differences in the group of PTSD on the processing of negative stimuli and changes in their frontal lobe activation. These preliminary results suggest that early traumatic experiences affect typical brain development patterns. And explicit and implicit variables involved in the traumatic experiences are discussed as a part of any intervention process.

Resumen El presente estudio tuvo como objetivo describir patrones de activación cerebral mediante una técnica de Imagen por resonancia magnética funcional -fMRI- (abreviatura en inglés de Functional Magnetic Resonance Imaging) en una muestra de niños con Trastorno de estrés postraumático (TEPT) y compararlos con un grupo de controles. Estudio cuasi-experimental en el que se tomó un grupo de 15 niños con TEPT y se comparó con un grupo de 7 niños sin TEPT. Se emplearon dos tareas experimentales: una prueba de caras y una versión del Stroop emocional. Los resultados preliminares, señalan diferencias en el procesamiento de estímulos, principalmente de carácter negativo en los niños con TEPT y cambios en los patrones de activación a nivel de estructuras frontales. Se concluye que el trauma a edad temprana afecta el curso normal del desarrollo cerebral y se evidencia la importancia de abordar los aspectos explícitos e implícitos asociados a la experiencia traumática como parte de la intervención.

Bacterial Contamination Analysis of Residential Toilet Room Environment and Delivery of Residual Bacterial Growth Prevention Efficacy on Residential Toilet Permeable Surfaces Using Toilet Air Freshener Product.

Toilet malodor is one of the most concerned malodor in residential houses, so that many technologies and products have been developed by which is aiming to remove or reduce such toilet malodor. Toilet malodour is generated from human faecal matters left inside of toilet bowl and from that deposited outside of toilet bowl such as toilet floors. In order to remove or prevent the malodor generated outside of toilet bowl, it is effective to do more frequent cleaning of toilet room surfaces or place a deodorizer which mask the malodour by perfume. We developed a toilet deodorizer which is preventing malodor generation outside of toilet bowl more effectively by delivering antibacterial efficacy on toilet room permeable surfaces. We analyzed microbiological quality of residential toilet rooms and found that toilet floor is the most contaminated location by bacteria, so that we developed a test method using materials frequently used for residential toilet floors such as vinyl cushion and using bacteria commonly found in toilet room environment. As the results, we found the product can provide bacterial growth prevention efficacy on permeable materials and prevent toilet malodor effectively.

Emotional memory processing in post-traumatic stress disorder affected Colombian youth.

Post-traumatic stress disorder (PTSD) is a neuropsychological condition caused by exposure to chronic stressors and extreme trauma. In past decades, Colombia (South America) has experienced high levels of armed conflict, which created an environment of chronic stress, resulting in an increased incidence of PTSD in children. Limited research exists on the effects of PTSD on emotional memory functioning of these Colombian youth living in chronically stressful environments. In the present study, 23 PTSD affected youth and 26 controls were asked to recall items from a memorised word list, as well as remembering details from a short emotional story. Although no significant differences were found for word list memory, deficits for emotional story content were found in the PTSD youth, particularly for facts involving negative emotional details. The latter may suggest a deficit in executive functioning for the integration of emotionally laden stimuli, perhaps induced as a by-product of their traumatic experiences.

Implicit processing of emotional words by children with Post-Traumatic Stress Disorder: An fMRI investigation / Procesamiento implícito de palabras emocionales en niños con Trastorno de Estrés Postraumático: investigación con resonancia magnética funcional

BACKGROUND/OBJECTIVE: In the last decade, socio-political violence in Colombia (South America) has created an environment of extreme/chronic stress. In this study, brain imaging technology (fMRI) and behavioral task performance were used to measure potential deficits in executive functioning for emotional processing in Colombian children. METHOD: Participants (22 Post-Traumatic Stress Disorder, PTSD and 22 neurotypical, NT) were asked to perform a word task with implicit emotional salience, which required them to report the color of the ink in which a positive, negative or neutral word was printed. RESULTS: Mixed design analysis of variance showed no group differences in accuracy for determining ink color when presented as a positive or neutral word. However, PTSD children were significantly less accurate (negative words) and notably slower (both positive and negative words) at determining ink color when presented in the context of an emotional word. PTSD processing of positive and negative words was associated with hypoactivation in the superior and middle frontal gyri of the right hemisphere in comparison to NT children. CONCLUSIONS: These results may reflect a deficit in executive functioning for emotionally laden stimuli, perhaps induced as a by-product of their traumatic experiences

ANTECEDENTES/OBJETIVO: En la última década, la violencia socio-política en Colombia, ha propiciado un ambiente generador de situaciones de estrés crónico/extremo. El presente estudio empleó resonancia magnética funcional, junto con tareas conductuales, para medir posibles déficits en el funcionamiento ejecutivo en una tarea de palabras con contenido emocional en una muestra de niños colombianos. MÉTODO: A los participantes (22 TEPT y 22 controles), se les pidió indicar el color de la palabra impresa, omitiendo el contenido emocional implícito positivo, neutro o negativo. RESULTADOS: El análisis de varianza de diseño mixto, no arrojó diferencias entre los grupos, en número de aciertos al determinar el color en que estaban impresas las palabras positivas o neutras. Sin embargo, los niños con TEPT tuvieron más errores con las palabras de contenido emocional negativo y fueron más lentos que los controles con palabras de valencia positiva o negativa. En cuanto a las palabras positivas y negativas, el grupo con TEPT se asoció a hipoactivación de los giros superior y medio frontal del hemisferio derecho, al compararlos con los controles. CONCLUSIONES: Estos resultados sugieren déficits en el funcionamiento ejecutivo para estímulos con contenido emocional, quizás como consecuencia de las experiencias traumáticas vividas por el grupo de TEPT

Implicit processing of emotional words by children with Post-Traumatic Stress Disorder: An fMRI investigation.

BACKGROUND/OBJECTIVE: In the last decade, socio-political violence in Colombia (South America) has created an environment of extreme/chronic stress. In this study, brain imaging technology (fMRI) and behavioral task performance were used to measure potential deficits in executive functioning for emotional processing in Colombian children. METHOD: Participants (22 Post-Traumatic Stress Disorder, PTSD and 22 neurotypical, NT) were asked to perform a word task with implicit emotional salience, which required them to report the color of the ink in which a positive, negative or neutral word was printed. RESULTS: Mixed design analysis of variance showed no group differences in accuracy for determining ink color when presented as a positive or neutral word. However, PTSD children were significantly less accurate (negative words) and notably slower (both positive and negative words) at determining ink color when presented in the context of an emotional word. PTSD processing of positive and negative words was associated with hypoactivation in the superior and middle frontal gyri of the right hemisphere in comparison to NT children. CONCLUSIONS: These results may reflect a deficit in executive functioning for emotionally laden stimuli, perhaps induced as a by-product of their traumatic experiences.

ANTECEDENTES/OBJETIVO: En la última década, la violencia socio-política en Colombia, ha propiciado un ambiente generador de situaciones de estrés crónico/extremo. El presente estudio empleó resonancia magnética funcional, junto con tareas conductuales, para medir posibles déficits en el funcionamiento ejecutivo en una tarea de palabras con contenido emocional en una muestra de niños colombianos. MÉTODO: A los participantes (22 TEPT y 22 controles), se les pidió indicar el color de la palabra impresa, omitiendo el contenido emocional implícito positivo, neutro o negativo. RESULTADOS: El análisis de varianza de diseño mixto, no arrojó diferencias entre los grupos, en número de aciertos al determinar el color en que estaban impresas las palabras positivas o neutras. Sin embargo, los niños con TEPT tuvieron más errores con las palabras de contenido emocional negativo y fueron más lentos que los controles con palabras de valencia positiva o negativa. En cuanto a las palabras positivas y negativas, el grupo con TEPT se asoció a hipoactivación de los giros superior y medio frontal del hemisferio derecho, al compararlos con los controles. CONCLUSIONES: Estos resultados sugieren déficits en el funcionamiento ejecutivo para estímulos con contenido emocional, quizás como consecuencia de las experiencias traumáticas vividas por el grupo de TEPT.

Inducción de estados afectivos a través de imágenes. Segunda validación colombiana del Sistema Internacional de Imágenes Afectivas (IAPS) / Induction of Affective States with Pictures: Second Colombian Validation of the International Affective Pictures System (IAPS)

Resumen El objetivo del presente estudio es validar un segundo grupo de imágenes del Sistema Internacional de Imágenes Afectiva (IAPS) en población colombiana, con el fin de aumentar el banco de imágenes que puedan ser utilizadas en investigaciones en los campos de la emoción, la atención y la memoria, entre otros. Se validaron 240 imágenes pertenecientes a los conjuntos 15, 16, 17 y 18 del IAPS en una muestra de 1.222 personas provenientes de cinco ciudades del país (Bogotá, Medellín, Cali, Barranquilla y Bucaramanga). Para evaluar la respuesta emocional ante las imágenes en las dimensiones de valencia, arousal y dominancia se utilizó el Self-Assessment Manikin (SAM). Los resultados mostraron que las imágenes se distribuyeron de la forma esperada en el espacio afectivo bidimensional compuesto por las dimensiones de valencia y arousal. Se identificó un sesgo emocional positivo en los hombres y un sesgo emocional negativo en las mujeres. Las diferencias entre regiones y estrato socioeconómico se presentaron únicamente en arousal y dominancia, no en valencia. En conjunto, los resultados sugieren que estas imágenes pueden ser utilizadas para inducir estados afectivos en la población colombiana de forma controlada, lo que permite su uso para el estudio científico y experimental de diferentes procesos psicológicos, como la emoción, la motivación y la atención.

Abstract The aim of this study was to validate a second group of images of the International Affective Pictures System (IAPS) in Colombian population, in order to increase the bank of images that can be used in research in the fields of emotion, attention and memory, among others. 240 pictures belonging to sets 15, 16, 17 and 18 of the IAPS were validated in a sample of 1222 participants from five cities in the country (Bogotá, Medellín, Cali, Barranquilla and Bucaramanga). To assess the emotional response to images in the valence, arousal and dominance dimensions, the Self-Assessment Manikin (SAM) was used. The results showed that the pictures were distributed as expected in the two-dimensional affective space composed of the valence and arousal dimensions. A positive emotional bias was identified in men and a negative emotional bias in women. The differences between regions and socioeconomic strata were presented only in arousal and dominance, not in valence. Together, the results suggest that these images can be used to induce affective states in the Colombian population in a controlled manner, which allows their use for the scientific and experimental study of different psychological processes, such as emotion, motivation and attention.

Cognitive profiles of Post-traumatic Stress Disorder and depression in children and adolescents / Perfiles cognitivos en el trastorno del trastorno de estrés postraumático y la depresión en niños y adolescentes

Background/Objective: Several diagnostic criteria of Post-traumatic Stress Disorder (PTSD) are remarkably similar to symptoms reported by individuals with depression, particularly as they manifest as cognitive processing deficits in children. Because of this overlap in profile and the high rate of comorbidity of PTSD and depression (48% to 69%), pinpointing similarities/differences in cognitive processes related to each of these disorders is essential to accurate diagnosis. This study aims to examine cognitive performance profiles of 23 children who have been victims of PTSD and to compare their results with 23 children with depression and 24 controls. Method: Empirical study, observational and descriptive methodologies were performed using several neuropsychological tests to assess IQ, attention, memory and executive function. Statistical comparisons between groups were made using the non-parametric Kruskall-Wallis test and post-hoc analyses were conducted using a Mann Whitney U test, as well as Quade's co-variance analysis. Results: Data show different profiles of cognitive performance in those with PTSD compared to those with depression and controls. Conclusions: The findings suggests that PTSD and depressed children differ somewhat in their cognitive profiles, and the differences in IQ found between those with PTSD and those without are not necessarily a confounding variable, but may rather be a consequence of their traumatic experience (AU)

Antecedentes/Objetivo: Varios criterios diagnósticos del trastorno de estrés post-traumático (PTSD, por sus siglas en inglés) son similares a los síntomas de la depresión, particularmente relacionados con aspectos cognitivos de niños afectados por estas condiciones. Debido a esta superposición del perfil cognitivo y dada la alta comorbilidad entre PTSD y depresión (48% y 69%), identificar las características en los perfiles cognitivos de cada trastorno pudiera ser útil para hacer diagnósticos más precisos. El objetivo fue examinar el rendimiento cognitivo en 23 niños con PTSD y comparar sus resultados con 23 niños con depresión y 24 controles. Método: Estudio empírico, observacional y descriptivo mediante aplicación de una batería neuropsicológica que evaluó inteligencia, atención, memoria y función ejecutiva. Las comparaciones estadísticas se realizaron mediante la prueba no paramétrica Kruskal-Wallis. Los análisis post-hoc se realizaron utilizando U de Mann Whitney y el análisis de covarianza de Quade. Resultados: Los datos muestran diferentes perfiles cognitivos del grupo con PTSD en comparación con los grupos de depresión y controles. Conclusiones: Los hallazgos sugieren que el grupo de PTSD y el grupo de depresión difieren en sus perfiles cognitivos y que las diferencias en el nivel intelectual encontradas en los niños con PTSD pudieran no ser una variable de confusión sino una consecuencia de la experiencia traumática (AU)

Changes in Cognitive Performance in a Sample of Children and Teens with Post-Traumatic Stress Disorder Resulting from the Armed Conflict in Colombia / Alteraciones en el funcionamiento cognitivo en una muestra de niños, niñas y adolescentes con trastorno de estrés postraumático derivado del conflicto armado en colombia

Resumen El objetivo del presente estudio fue comparar el perfil de funcionamiento cognitivo de una muestra de niños, niñas y adolescentes con Trastorno de Estrés Postraumático (TEPT) derivado del conflicto armado en Colombia con un grupo de control. La muestra estuvo conformada por 50 participantes: 25 de ellos con TEPT, víctimas de situaciones asociadas a conflicto armado y 25 provenientes de la misma zona geográfica sin antecedentes de haber vivido tales situaciones. Los grupos fueron equiparados en edad, género, nivel socioeconómico y nivel académico. Las pruebas aplicadas evaluaron la atención, la memoria y el funcionamiento ejecutivo. Los resultados señalan que los niños y adolescentes con TEPT presentan un perfil neuropsicológico caracterizado por dificultades en los procesos de atención visual para material verbal y no verbal, alteraciones en la memoria lógica, con conservación de la habilidad para realizar actividades de aprendizaje verbal y marcado compromiso en el funcionamiento ejecutivo, mostrando alteraciones en pruebas que implican control inhibitorio, pocas habilidades para monitorear la conducta y dificultades en tareas que implican flexibilidad cognitiva. Con base en los resultados, se propone un perfil de funcionamiento cognitivo de los niños y adolescentes con TEPT, que coadyuve los procesos de evaluación e intervención en el marco de los procesos de reparación integral del post conflicto en Colombia.

Abstract The aim of this study was to compare the cognitive functioning profile between a sample of children and adolescences with Post-Traumatic Stress Disorder (PTSD) derived from the arm conflict in Colombia and a control group. This study compared neuropsychological test results from a group of 50 children, 25 of them victims of an associated armed conflict situation with PTSD and 25 from the same geographical zone, without a record of going through such situation. The groups were matched by age, sex, socioeconomic status and education level. A battery of tests that assessed attention, memory and executive function was conducted. The results indicate that children with PTSD evidence a neuropsychological profile characterized by difficulties in the processes of visual attention in relation to verbal and nonverbal materials, logical memory disorders, with ability to perform verbal learning activities and notorious incidence in executive functioning. Assessment indicates changes that imply inhibitory control, poor ability to monitor the behavior, and difficulties in task that involve cognitive flexibility. Based on these scores, it is proposed a profile of cognitive functioning in children and adolescents with PTSD that could be useful to conduct more accurate assessment and clinical interventions within the framework of the Colombian post conflict process.

Cognitive profiles of Post-traumatic Stress Disorder and depression in children and adolescents.

Background/Objective: Several diagnostic criteria of Post-traumatic Stress Disorder (PTSD) are remarkably similar to symptoms reported by individuals with depression, particularly as they manifest as cognitive processing deficits in children. Because of this overlap in profile and the high rate of comorbidity of PTSD and depression (48% to 69%), pinpointing similarities/differences in cognitive processes related to each of these disorders is essential to accurate diagnosis. This study aims to examine cognitive performance profiles of 23 children who have been victims of PTSD and to compare their results with 23 children with depression and 24 controls. Method: Empirical study, observational and descriptive methodologies were performed using several neuropsychological tests to assess IQ, attention, memory and executive function. Statistical comparisons between groups were made using the non-parametric Kruskall-Wallis test and post-hoc analyses were conducted using a Mann Whitney U test, as well as Quade's co-variance analysis. Results: Data show different profiles of cognitive performance in those with PTSD compared to those with depression and controls. Conclusions: The findings suggests that PTSD and depressed children differ somewhat in their cognitive profiles, and the differences in IQ found between those with PTSD and those without are not necessarily a confounding variable, but may rather be a consequence of their traumatic experience.

Antecedentes/Objetivo: Varios criterios diagnósticos del trastorno de estrés post-traumático (PTSD, por sus siglas en inglés) son similares a los síntomas de la depresión, particularmente relacionados con aspectos cognitivos de niños afectados por estas condiciones. Debido a esta superposición del perfil cognitivo y dada la alta comorbilidad entre PTSD y depresión (48% y 69%), identificar las características en los perfiles cognitivos de cada trastorno pudiera ser útil para hacer diagnósticos más precisos. El objetivo fue examinar el rendimiento cognitivo en 23 niños con PTSD y comparar sus resultados con 23 niños con depresión y 24 controles. Método: Estudio empírico, observacional y descriptivo mediante aplicación de una batería neuropsicológica que evaluó inteligencia, atención, memoria y función ejecutiva. Las comparaciones estadísticas se realizaron mediante la prueba no paramétrica Kruskal-Wallis. Los análisis post-hoc se realizaron utilizando U de Mann Whitney y el análisis de covarianza de Quade. Resultados: Los datos muestran diferentes perfiles cognitivos del grupo con PTSD en comparación con los grupos de depresión y controles. Conclusiones: Los hallazgos sugieren que el grupo de PTSD y el grupo de depresión difieren en sus perfiles cognitivos y que las diferencias en el nivel intelectual encontradas en los niños con PTSD pudieran no ser una variable de confusión sino una consecuencia de la experiencia traumática.

Perfil neuropsicológico del trastorno por estrés postraumático agudo en una muestra de personas, víctimas de un atentado con carro-bomba en Colombia: estudio descriptivo* / Neuropsychological profile of post traumatic stress disorder acute in a sample of victims from car-bomb attack in Colombia

Objetivo: describir el rendimiento cognitivo en un grupo de personas afectadas por un atentado con carro bomba. Materiales y métodos: estudio descriptivo correlacional que incluyó una muestra de 50 participantes divididos en dos grupos: uno conformado por 25 participantes que vivieron una situación traumática asociada a un atentado con carro bomba, en las instalaciones donde laboraban. El otro grupo estuvo conformado por 25 partipantes que trabajaban en la misma institución pero no han tenido antecedentes de eventos traumáticos. Los grupos fueron equiparados entre sí en las variables demográficas de sexo, edad, nivel socioeconómico y académico, y estado civil. Las pruebas aplicadas evaluaron los dominios cognitivos de atención, memoria y función ejecutiva. Resultados:al comparar el desempeño de ambos grupos, se encontraron diferencias significativas en pruebas que evaluan la integridad del lóbulo frontal. Conclusiones: se discute la necesidad de tomar en cuenta tanto la diferencia de tipo estadístico como la relevancia clínica de los resultados y se ofrecen sugerencias para incluir dentro de los aspectos de evaluación e intervención de las víctimas con estrés postraumático variables de tipo neuropsicológico que pueden afectar los procesos de reinserción laboral y académico...(AU)

Objetive: the aim of the present study is to describe the cognitive performance on group of people whom have lived trough situations involving traumas associated with car bombings at their work facilities. Material and Methods: descriptive and correlational study that included a sample of 50 patients divided in two groups: one made up of 25 participants that were affected by traumatic experience associated with car bombing. In the other group of 25, participants that worked in the same facility; but have not had, any type of traumatic events. The groups were assimilated in various demographic variables; sex, age, socioeconomic, marital, and academic status. Thetests were applied and evaluated cognitive domains of attention, memory and executive functioning. Results: comparison between both groups shows differences in the executive function tests, which may be related to alterations in the functioning of the frontal lobe. Conclusion: it is to discuss the need to take into account both the different statistics and the clinical relevance of the results, and offering the suggestion to include an assessment and intervention of the victims with post-traumatic stress variables of Neuropsychological aspects that can affect, reintegration and academic processes...(AU)

Perfil neuropsicológico del trastorno por estrés postraumático agudo en una muestra de personas, víctimas de un atentado con carro-bomba en Colombia: estudio descriptivo / Neuropsychological profile of post traumatic stress disorder acute in a sample of victims from carbomb attack in Colombia: descriptive study

Objetivo: describir el rendimiento cognitivo en un grupo de personas afectadas por un atentado con carro bomba. Materiales y métodos: estudio descriptivo correlacional que incluyó una muestra de 50 participantes divididos en dos grupos: uno conformado por 25 participantes que vivieron una situación traumática asociada a un atentado con carro bomba, en las instalaciones donde laboraban. El otro grupo estuvo conformado por 25 partipantes que trabajaban en la misma institución pero no han tenido antecedentes de eventos traumáticos. Los grupos fueron equiparados entre sí en las variables demográficas de sexo, edad, nivel socioeconómico y académico, y estado civil. Las pruebas aplicadas evaluaron los dominios cognitivos de atención, memoria y función ejecutiva. Resultados: al comparar el desempeño de ambos grupos, se encontraron diferencias significativas en pruebas que evaluan la integridad del lóbulo frontal. Conclusiones: se discute la necesidad de tomar en cuenta tanto la diferencia de tipo estadístico como la relevancia clínica de los resultados y se ofrecen sugerencias para incluir dentro de los aspectos de evaluación e intervención de las víctimas con estrés postraumático variables de tipo neuropsicológico que pueden afectar los procesos de reinserción laboral y académico.

Objetive: the aim of the present study is to describe the cognitive performance ongroup of people whom have lived trough situations involving traumas associated withcar bombings at their work facilities. Material and Methods: descriptive and correlationalstudy that included a sample of 50 patients divided in two groups: one madeup of 25 participants that were affected by traumatic experience associated with carbombing. In the other group of 25, participants that worked in the same facility; buthave not had, any type of traumatic events. The groups were assimilated in various demographic variables; sex, age, socioeconomic, marital, and academic status. The tests were applied and evaluated cognitive domains of attention, memory and executive functioning. Results: comparison between both groups shows differences in the executive function tests, which may be related to alterations in the functioning of the frontal lobe. Conclusion: it is to discuss the need to take into account both the different statistics and the clinical relevance of the results, and of fering the suggestion to include an assessment and intervention of the victims with post-traumatic stress variables of Neuropsychological aspects that can affect, reintegration and academic processes.

Hospital 360°.

There are forces that are greater than the individual performance of each hospital institution and of the health system structural of each country. The world is changing and to face up to the future in the best possible way, we need to understand how contexts and emerging trends link up and how they affect the hospital sector. The Columbian Association of Hospitals and Clinics, ACHC, has thus come up with the Hospital 360° concept which uses hospitals capable of anticipating changing contexts by means of the transition between present and future and takes on board the experience of global, socio-economic, demographic, political, environmental and technological fields as its model. Hospital 360° is an invitation to reinvent processes and institution themselves allowing them to adapt and incorporate a high degree of functional flexibility. Hospital 360° purses goals of efficiency, effectiveness and relevance, but also of impact and sustainability, and is coherent with the internal needs of hospital institutions and society for long-term benefits.

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors.

PURPOSE: This phase I study evaluated the safety, maximum tolerated dose, antitumor activity, and pharmacokinetics and pharmacodynamics of pembrolizumab in patients with advanced solid tumors. EXPERIMENTAL DESIGN: In a 3 + 3 dose escalation study, 10 patients received pembrolizumab 1, 3, or 10 mg/kg intravenously every 2 weeks until progression or intolerable toxicity. Seven additional patients received 10 mg/kg every 2 weeks. Thirteen patients participated in a 3-week intrapatient dose escalation (dose range, 0.005-10 mg/kg) followed by 2 or 10 mg/kg every 3 weeks. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: No dose-limiting toxicities were observed. Maximum administered dose was 10 mg/kg every 2 weeks. One patient with melanoma and one with Merkel cell carcinoma experienced complete responses of 57 and 56+ weeks' duration, respectively. Three patients with melanoma experienced partial responses. Fifteen patients with various malignancies experienced stable disease. One patient died of cryptococcal infection 92 days after pembrolizumab discontinuation, following prolonged corticosteroid use for grade 2 gastritis considered drug related. Pembrolizumab exhibited pharmacokinetic characteristics typical of humanized monoclonal antibodies. Maximum serum target engagement was reached with trough levels of doses greater than or equal to 1 mg/kg every 3 weeks. Mechanism-based translational models with a focus on intratumor exposure prediction suggested robust clinical activity would be observed at doses ≥2 mg/kg every 3 weeks. CONCLUSIONS: Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors. The lowest dose with full potential for antitumor activity was 2 mg/kg every 3 weeks.

Influence of Pre-Analytical Factors on Thymus- and Activation-Regulated Chemokine Quantitation in Plasma.

Thymus- and activation-regulated chemokine (TARC) in serum/plasma associates with the disease activity of atopic dermatitis (AD), and is a promising tool for assessing the response to the treatment of the disease. TARC also exists within platelets, with elevated levels detectable in AD patients. We examined the effects of pre-analytical factors on the quantitation of TARC in human EDTA plasma. TARC levels in platelet-free plasma were significantly lower than those in platelet-containing plasma. After freeze-thaw, TARC levels increased in platelet-containing plasma, but remained unchanged in platelet-free plasma, suggesting TARC was released from the platelets during the freeze-thaw process. In contrast, TARC levels were stable in serum independent of freeze-thaw. These findings underscore the importance of pre-analytical factors to TARC quantitation. Plasma TARC levels should be measured in platelet-free plasma for accurate quantitation. Pre-analytical factors influence the quantitation, interpretation, and implementation of circulating TARC as a biomarker for the development of AD therapeutics.

Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.

PURPOSE: Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60 mg on alternate days (QOD). Due to a long half-life (60-80 hours), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. EXPERIMENTAL DESIGN: Patients with advanced cancers were enrolled in a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy, and intrinsic susceptibility-weighted MRI. RESULTS: A total of 71 patients were enrolled; 38 patients had 60 mg MK-2206 QOD, whereas 33 received MK-2206 at 90, 135, 150, 200, 250, and 300 mg QW. The QW MK-2206 MTD was established at 200 mg following dose-limiting rash at 250 and 300 mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial. CONCLUSIONS: Treatment with MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200 mg QW is currently used in phase II MK-2206 monotherapy and combination studies (NCT00670488).

¿Es efectivo el entrenamiento en Neurofeedback para el tratamiento del TDAH? Resultados a partir de una revisión sistemática / Is Neurofeedback training an efficacious treatment for ADHD? Results from a systematic review

El objetivo del presente trabajo es establecer, a partir de la revisión sistemática de artículos empíricos publicados entre 2001 y 2011, la viabilidad del uso del Neurofeedback como técnica de entrenamiento para disminuir los síntomas del Trastorno por déficit de atenciónhiperactividad en población infantil y adolescente. Se identificaron 88 artículos y con base en los criterios de inclusión definidos previamente, se seleccionó un total de 11 artículos. La evaluación de eficacia se hizo con base en los criterios definidos por la Asociación de Psicofisiología Aplicada y Biofeedback (Association for Applied Psychophysiology and Biofeedback AAPB). Los resultados apuntan a un nivel de eficacia situado entre nivel dos (posible eficacia) y nivel tres (eficacia probable), por lo que se hace necesario la realización de investigaciones con un mayor nivel de control de variables y en muestras más amplias. Se discuten aspectos relacionados con su uso clínico y metodológico para futuros estudios.

Based on a systematic review of empirical articles published between 2001 and 2011, this study aims to establish the viability of using Neurofeedback training as a technique to reduce the symptoms of attention deficit hyperactivity disorder in children and teenager. 88 articles were identified and based on the defined inclusion criteria, and 11 articles were selected. Evaluation of efficacy was based on the criteria defined by the Association of Applied Psychophysiology and Biofeedback (Association for Applied Psychophysiology and Biofeedback AAPB ). The results point to a level of efficacy located between level two (potential effectiveness) and level three (probable effectiveness), therefore, it is necessary to conduct a research with a higher level of control of variables and larger samples. Related clinical uses and methodological aspects are discussed for future studies.

An ultra-sensitive clinical biomarker assay: quantitation of thymus and activation-regulated chemokine in human plasma.

BACKGROUND: Thymus and activation-regulated chemokine (TARC) is a Th2 type, pro-allergic secreted chemokine. TARC in plasma/serum has been proposed as a marker for disease activity of atopic dermatitis (AD) and as a pharmacodynamic readout in the clinical development of novel agents for the treatment of AD. RESULTS: An ultra-sensitive electrochemiluminescence assay for TARC in human plasma was developed and analytically validated. The assay demonstrated excellent performance characteristics, including precision, sensitivity, dilution linearity, accuracy and specificity. Stability and biological variability of TARC in plasma were also assessed for clinical sample analysis and data interpretation. CONCLUSION: The improved sensitivity allowed the measurement of approximately 90% TARC inhibition from baseline levels of healthy subjects and >90% TARC inhibition from baseline levels of AD patients after drug treatment. A validated TARC electrochemiluminescence assay enables pharmacodynamic assessment in the development of AD therapeutics.