Accurate calling of KIAA1549-BRAF fusions from DNA of human brain tumours using methylation array-based copy number and gene panel sequencing data.

AIMS: KIAA1549-BRAF fusions occur in certain brain tumours and provide druggable targets due to a constitutive activation of the MAP-kinase pathway. We introduce workflows for calling the KIAA1549-BRAF fusion from DNA methylation array-derived copy number as well as DNA panel sequencing data. METHODS: Copy number profiles were analysed by automated screening and visual verification of a tandem duplication on chromosome 7q34, indicative of the KIAA1549-BRAF fusion. Pilocytic astrocytomas of the ICGC cohort with known fusion status were used for validation. KIAA1549-BRAF fusions were called from DNA panel sequencing data using the fusion callers Manta, Arriba with modified filtering criteria and deFuse. We screened DNA methylation and panel sequencing data of 7790 specimens from brain tumour and sarcoma entities. RESULTS: We identified the fusion in 337 brain tumours with both DNA methylation and panel sequencing data. Among these, we detected the fusion from copy number data in 84% and from DNA panel sequencing data in more than 90% using Arriba with modified filters. While in 74% the KIAA1549-BRAF fusion was detected from both methylation array-derived copy number and panel sequencing data, in 9% it was detected from copy number data only and in 16% from panel data only. The fusion was almost exclusively found in pilocytic astrocytomas, diffuse leptomeningeal glioneuronal tumours and high-grade astrocytomas with piloid features. CONCLUSIONS: The KIAA1549-BRAF fusion can be reliably detected from either DNA methylation array or DNA panel data. The use of both methods is recommended for the most sensitive detection of this diagnostically and therapeutically important marker.

Relative influence of environmental factors and fishing on coral reef fish assemblages.

Understanding whether assemblages of species respond more strongly to bottom-up (availability of trophic resources or habitats) or top-down (predation pressure) processes is important for effective management of resources and ecosystems. We determined the relative influence of environmental factors and predation by humans in shaping the density, biomass, and species richness of 4 medium-bodied (10-40 cm total length [TL]) coral reef fish groups targeted by fishers (mesopredators, planktivores, grazer and detritivores, and scrapers) and the density of 2 groups not targeted by fishers (invertivores, small fish ≤10 cm TL) in the central Philippines. Boosted regression trees were used to model the response of each fish group to 21 predictor variables: 13 habitat variables, 5 island variables, and 3 fishing variables (no-take marine reserve [NTMR] presence or absence, NTMR size, and NTMR age). Targeted and nontargeted fish groups responded most strongly to habitat variables, then island variables. Fishing (NTMR) variables generally had less influence on fish groups. Of the habitat variables, live hard coral cover, structural complexity or habitat complexity index, and depth had the greatest effects on density, biomass, and species richness of targeted fish groups and on the density of nontargeted fishes. Of the island variables, proximity to the nearest river and island elevation had the most influence on fish groups. The NTMRs affected only fishes targeted by fishers; NTMR size positively correlated with density, biomass, and species richness of targeted fishes, particularly mesopredatory, and grazing and detritivorous fishes. Importantly, NTMRs as small as 15 ha positively affected medium-bodied fishes. This finding provides reassurance for regions that have invested in small-scale community-managed NTMRs. However, management strategies that integrate sound coastal land-use practices to conserve adjacent reef fish habitat, strategic NTMR placement, and establishment of larger NTMRs will be crucial for maintaining biodiversity and fisheries.

Influencia Relativa de los Factores Ambientales y la Pesca sobre el Ensamblaje de Peces en los Arrecifes de Coral Resumen Es importante entender si el ensamblaje de especies responde con mayor fuerza al proceso de abajo-arriba (disponibilidad de recursos tróficos o hábitats) o al de arriba-abajo (presión de depredadores) para el manejo efectivo de los recursos y los ecosistemas. Determinamos la influencia relativa de los factores ambientales y la depredación humana en la configuración de la densidad, la biomasa y la riqueza de especies de cuatro peces de arrecife de coral con un tamaño corporal mediano (10-40 cm de longitud total [LT]) que son preferidos por los pescadores (mesodepredadores, planctívoros, forrajeros y detritívoros, y raspadores) y también determinamos la densidad de dos grupos que no son blanco de los pescadores (invertívoros y peces de talla pequeña ≤10 cm LT) en la región central de las Filipinas. Usamos árboles de regresión amplificados para modelar la respuesta de cada grupo de peces a 21 variables de predicción: trece variables de hábitat, cinco variables de isla y tres variables de pesca (ausencia o presencia de una reserva marina vedada [RMV], tamaño y antigüedad de la NTMR). Los grupos de peces preferidos y no preferidos por los pescadores respondieron con mayor fuerza a las variables de hábitat que a las variables de isla. Las variables de pesca (RMV) en general tuvieron una menor influencia sobre los grupos de peces. De las variables de hábitat, la cobertura de coral duro vivo, la complejidad estructural o el índice de complejidad del hábitat y la profundidad tuvieron el mayor efecto sobre la densidad, la biomasa y la riqueza de especies de los peces preferidos por los pescadores y sobre la densidad de los peces no preferidos por los pescadores. De las variables de isla, la proximidad al río más cercano y la elevación de la isla tuvieron la mayor influencia sobre los grupos de peces. Las RMVs afectaron sólo a los peces preferidos por los pescadores; el tamaño de la NTMR tuvo una correlación positiva con la densidad, la biomasa y la riqueza de especies de los peces preferidos por los pescadores, particularmente los peces mesodepredadores, forrajeros y detritívoros. De manera importante, las RMVs con un tamaño mínimo de 15 ha afectaron positivamente a los peces de talla mediana. Este hallazgo proporciona seguridad para las regiones que han invertido en RMVs de pequeña escala y manejadas por la comunidad. Sin embargo, las estrategias de manejo que integran prácticas firmes de uso de suelo costero para conservar el hábitat adyacente de peces, la ubicación estratégica de RMV y el establecimiento de RMVs más grandes serán cruciales para el mantenimiento de la biodiversidad y las pesquerías.

Effect of the growing area on the fat content and the fatty acid composition of Ecuadorian cocoa beans.

Cocoa presents a high fat content and a unique fatty acid profile defining its technological and nutritional properties. This study evaluated the fat content and fatty acid composition of Nacional cocoas, a worldwide recognised "fine" variety, collected in 85 Ecuadorian farms while taking into account 3 geographical levels (region, province, and canton). The total fat content varied from 45.61 ± 1.27 to 52.13 ± 0.58 g/100 g DW and was higher in the provinces and cantons from the Amazonian region than in those from the Pacific Coast region. A remarkable effect of the region and the province was shown on the content of individual fatty acids of Nacional cocoa beans. Total amounts of saturated and unsaturated fatty acids also depended on the growing area. Multivariate analysis provided a comprehensive assessment of the cocoa fat composition according to the origin, which may be useful for the selection of cocoas with specific technological and nutritional characteristics.

Differentiation of Ecuadorian National and CCN-51 cocoa beans and their mixtures by computer vision.

BACKGROUND: Ecuador exports two major types of cocoa beans, the highly regarded and lucrative National, known for its fine aroma, and the CCN-51 clone type, used in bulk for mass chocolate products. In order to discourage exportation of National cocoa adulterated with CCN-51, a fast and objective methodology for distinguishing between the two types of cocoa beans is needed. RESULTS: This study reports a methodology based on computer vision, which makes it possible to recognize these beans and determine the percentage of their mixture. The methodology was challenged with 336 samples of National cocoa and 127 of CCN-51. By excluding the samples with a low fermentation level and white beans, the model discriminated with a precision higher than 98%. The model was also able to identify and quantify adulterations in 75 export batches of National cocoa and separate out poorly fermented beans. CONCLUSION: A scientifically reliable methodology able to discriminate between Ecuadorian National and CCN-51 cocoa beans and their mixtures was successfully developed. © 2017 Society of Chemical Industry.

Impact of conservation areas on trophic interactions between apex predators and herbivores on coral reefs.

Apex predators are declining at alarming rates due to exploitation by humans, but we have yet to fully discern the impacts of apex predator loss on ecosystem function. In a management context, it is critically important to clarify the role apex predators play in structuring populations of lower trophic levels. Thus, we examined the top-down influence of reef sharks (an apex predator on coral reefs) and mesopredators on large-bodied herbivores. We measured the abundance, size structure, and biomass of apex predators, mesopredators, and herbivores across fished, no-take, and no-entry management zones in the Great Barrier Reef Marine Park, Australia. Shark abundance and mesopredator size and biomass were higher in no-entry zones than in fished and no-take zones, which indicates the viability of strictly enforced human exclusion areas as tools for the conservation of predator communities. Changes in predator populations due to protection in no-entry zones did not have a discernible influence on the density, size, or biomass of different functional groups of herbivorous fishes. The lack of a relationship between predators and herbivores suggests that top-down forces may not play a strong role in regulating large-bodied herbivorous coral reef fish populations. Given this inconsistency with traditional ecological theories of trophic cascades, trophic structures on coral reefs may need to be reassessed to enable the establishment of appropriate and effective management regimes.

Patients' perspectives on a patient-oriented electronic decision support tool to reduce overuse of proton pump inhibitors (arriba-PPI): a qualitative study in primary care.

BACKGROUND: To evaluate patients' perspectives and their experiences with a consultation involving a computer-assisted and patient-centered discontinuation strategy (arriba-PPI tool) as part of a German multicenter study on reducing the prescription of proton pump inhibitors (PPIs). METHODS: Qualitative in-depth telephone interviews on proton pump inhibitors with patients who had received an arriba-PPI tool-based counseling by their general practitioner (GP). A random sample of 30 patients was taken from study participants. Interviews were conducted in 2020 and analyzed using a thematic qualitative text analysis. RESULTS: Although this was meant to be the key to shared decision making with regard to PPI reduction, study participants mostly did not recall the visual features of the tool. However, a few patients remembered them very clearly. Above all, patients appreciated a trustful relationship with the GP as well as comprehensive, individualized counseling. CONCLUSION: Application of the arriba-PPI tool can support the decision process but can also hinder the consultation process if the tool is not properly embedded in the consultation. GPs using the arriba-PPI tool to support the shared decision-making process should consider the patients' and their own expectations on the benefit of the visual representation of the tool.

Abiotic Factors from Different Ecuadorian Regions and Their Contribution to Antioxidant, Metabolomic and Organoleptic Quality of Theobroma cacao L. Beans, Variety "Arriba Nacional".

Fine flavor cocoa is a unique category of cocoa that produces almonds with high aromatic potential and several sensory benefits that make it different from the basic or ordinary cocoas. Ecuador is the world's leader in the production and export of fine flavor cocoa, responsible for 63% of the world's total production due to the commercialization of the Arriba Nacional variety, known to possess an intense aroma that is unique in the cocoa world market. Besides its organoleptic specificity, this variety represents a source of important bioactive compounds associated with both sensory and health properties. This study evaluates the influence of an abiotic factor, nutritional soil status, on the phytochemical composition (methylxantines and phenolic compounds), and antioxidant and sensory properties of Arriba variety cocoa beans originating from three different geographical regions of Ecuador. We used the Diagnosis and Recommendation Integrated System (DRIS), Folin-Ciocalteau, high-performance liquid chromatography (HPLC), ABTS free-radical-scavenging activity, the α, α-diphenyl-ß-picrylhydrazyl free-radical-scavenging method (DPPH), and Ferric reducing antioxidant power (FRAP) analysis to reveal a significant correlation between Mn ions and total phenolic content, a positive implication of N in methylxanthine composition and antioxidant properties, and the importance of Ca, Mg, and K ions in increasing the flavonoid and anthocyanin content of raw cocoa beans. We showed that these nutritional elements can interfere with the nutraceutical and sensory properties of cocoa beans, as Cu, Mg, and K are correlated with anthocyaninic content, while Fe, Ca, P and Zn influenced the flavonoid content. We underline that the Arriba variety is suitable not only for the production of high-quality chocolate, but also for the increasing worldwide nutraceutical market, generating qualitative and competitive products.

In Vitro CRISPR-Cpf1 Assay for Differentiation of Fine and Bulk Cocoa (Theobroma cacao L.).

Cocoa cultivation is dominated by the clone "Colleción Castro Naranjal 51" (CCN-51). In contrast, CCN-51 is the expensive and aromatic fine cocoa "Arriba Nacional" from Ecuador. The differences in the overall quality of the beans and in the prices show that it is necessary to develop a rapid and accurate method to distinguish these varieties and prevent food fraud. To this end, we used a CRISPR-Cpf1 assay suitable for AT-rich targets such as the chloroplast genome (cpGenome). SNPs in cocoa plastid genomes were selected to replace the canonical PAM sequence of Cpf1 (5'-TTTV-3'). We developed two assay systems to digest both Arriba and CCN-51. The results were tested qualitatively by agarose gel electrophoresis and quantitatively by capillary gel electrophoresis. Using the assay described here, we were able to reliably detect admixtures of 5% CCN-51 (P < 0.01) and 10% Arriba (P < 0.05). The application to processed cocoa products was also successful.

Somatic experiencing - effectiveness and key factors of a body-oriented trauma therapy: a scoping literature review.

Background: The body-oriented therapeutic approach Somatic Experiencing® (SE) treats post-traumatic symptoms by changing the interoceptive and proprioceptive sensations associated with the traumatic experience. Filling a gap in the landscape of trauma treatments, SE has attracted growing interest in research and therapeutic practice, recently. Objective: To date, there is no literature review of the effectiveness and key factors of SE. This review aims to summarize initial findings on the effectiveness of SE and to outline method-specific key factors of SE. Method: To gain a first overview of the literature, we conducted a scoping review including studies until 13 August 2020. We identified 83 articles of which 16 fit inclusion criteria and were systematically analysed. Results: Findings provide preliminary evidence for positive effects of SE on PTSD-related symptoms. Moreover, initial evidence suggests that SE has a positive impact on affective and somatic symptoms and measures of well-being in both traumatized and non-traumatized samples. Practitioners and clients identified resource-orientation and use of touch as method-specific key factors of SE. Yet, an overall studies quality assessment as well as a Cochrane analysis of risk of bias indicate that the overall study quality is mixed. Conclusions: The results concerning effectiveness and method-specific key factors of SE are promising; yet, require more support from unbiased RCT-research. Future research should focus on filling this gap.

Antecedentes: Somatic Experiencing® (SE), abordaje terapéutico enfocado en el cuerpo, trata los síntomas postraumáticos mediante al modificación de las sensaciones interoceptivas y propioceptivas asociadas a la experiencia traumática. Al subsanar una brecha en el repertorio de tratamientos para el trauma, la ES ha atraído recientemente un creciente interés en investigación y en la práctica terapéutica.Objetivo: A la fecha, no existe una revisión de la literatura sobre la efectividad y los factores clave de la ES. Esta revisión tiene por objetivo el resumir los hallazgos iniciales sobre la efectividad de la ES y describir los factores claves específicos del método aplicado en la ES.Métodos: Para obtener un primer panorama general de la literatura, realizamos una revisión del alcance de la literatura incluyendo estudios publicados hasta el 13 de agosto del 2020. Identificamos 83 artículos, de los cuales 16 cumplían con los criterios de inclusión y fueron analizados de manera sistemática.Resultados: Los hallazgos brindan evidencia preliminar sobre efectos positivos de la ES en síntomas relacionados al trastorno de estrés postraumático (TEPT). Asimismo, la evidencia inicial sugiere que la ES tiene un impacto positivo sobre síntomas afectivos y somáticos, y sobre indicadores de bienestar tanto en muestras de personas traumatizadas como en no traumatizadas. Los facultativos y los clientes identificaron recursos de orientación y el uso del tacto como los factores clave específicos del método aplicado en la ES. Sin embargo, tanto una evaluación general de la calidad de los estudios como un análisis Cochrane para el riesgo de sesgo mostraron que la calidad general del estudio es mixta.Conclusiones: Los resultados relacionados a la efectividad y a los factores clave específicos del método aplicado en la ES son prometedores; no obstante, se requiere mayor sustento proveniente de ensayos clínicos aleatorizados sin sesgo. Las investigaciones futuras deberían enfocarse en subsanar esta brecha.

The Optimizing-Risk-Communication (OptRisk) randomized trial - impact of decision-aid-based consultation on adherence and perception of cardiovascular risk.

BACKGROUND: Shared decision-making is a well-established approach to increasing patient participation in medical decisions. Increasingly, using lifetime-risk or time-to-event (TTE) formats has been suggested, as these might have advantages in comparison with a 10-year risk prognosis, particularly for younger patients, whose lifetime risk for some events may be considerably greater than their 10-year risk. In this study, a randomized trial, the most popular 10-year risk illustration in the decision-aid software Arriba (emoticons), is compared with a newly developed TTE illustration, which is based on a Markov model. The study compares the effect of these two methods of presenting cardiovascular risk to patients on their subsequent adherence to intervention. METHODS: A total of 294 patients were interviewed 3 months after they had had a consultation with their GP on cardiovascular risk prevention. Adherence to behavioral change or medication intervention was measured as the primary outcome. The latter was expressed as a generated score. Furthermore, different secondary outcomes were measured, ie, patient perception of risk and self-rated importance of avoiding a cardiovascular event, as well as patient numeracy, which was used as a proxy for patient health literacy. RESULTS: Overall, no significant difference in patient adherence was found depending on risk representation. In the emoticon group, the number of interventions had a significant impact on the adherence score (P=0.025). Perception of risk was significantly higher in patients counseled with the TTE risk display, whereas the importance of avoiding a cardiovascular event was rated equally highly in both groups and actually increased over time. CONCLUSION: The TTE format is an appropriate means for counseling patients. Adherence is a very complex construct, which cannot be fully explained by our findings. The study results support our call for considering TTE illustrations as a valuable alternative to current decision-support tools covering cardiovascular prevention. Nevertheless, further research is needed to shed light on patient motivation and adherence with regard to cardiovascular risk prevention. TRIAL REGISTRATION: The study was registered at the German Clinical Trials Register and at the WHO International Clinical Trials Register Platform (ICTRP, ID DRKS00004933); registered February 2, 2016 (retrospectively registered).

DNA-based differentiation of the Ecuadorian cocoa types CCN-51 and Arriba based on sequence differences in the chloroplast genome.

Two cocoa types, Arriba and CCN-51, are being cultivated in Ecuador. With regard to the unique aroma, Arriba is considered a fine cocoa type, while CCN-51 is a bulk cocoa because of its weaker aroma. Because it is being assumed that Arriba is mixed with CCN-51, there is an interest in the analytical differentiation of the two types. Two methods to identify CCN-51 adulterations in Arriba cocoa were developed on the basis of differences in the chloroplast DNA. On the one hand, a different repeat of the sequence TAAAG in the inverted repeat region results in a different length of amplicons for the two cocoa types, which can be detected by agarose gel electrophoresis, capillary gel electrophoresis, and denaturing high-performance liquid chromatography. On the other hand, single nucleotide polymorphisms (SNPs) between the CCN-51 and Arriba sequences represent restriction sites, which can be used for restriction fragment length polymorphism analysis. A semi-quantitative analysis based on these SNPs is feasible. A method for an exact quantitation based on these results is not realizable. These sequence variations were confirmed for a comprehensive cultivar collection of Arriba and CCN-51, for both bean and leaf samples.

La gobernabilidad migratoria en Sudamérica: la difusión de abajo hacia arriba (ascendente) del Acuerdo de Residencia del Mercosur / Migration governance in south america: the bottom-up diffusion of the residence agreement of mercosur / A governança migratória na américa do sul: a difusão de baixo para cima (bottom-up) do acordo de residência do mercosul

Abstract This article offers a complementary explanation to the diffusion theory that focuses on the process of governance emergence from a top-down perspective. This complementary explanation analyzes the bottom-up processes of diffusion and tested them by studying the policy formulation process in the Mercosur Residence Agreement (RA) signed in 2002. Based on interviews with key actors, documents, and academic literature, this article concludes that the RA was mainly the result of Brazilian and Argentinian negotiations. Brazil needed to boost regional cooperation after the Mercosur crisis, and considered that a joint migration amnesty could have a positive impact on the trading bloc's image. However, the Argentinian experience in migration issues allowed for a more coherent policy on the matter. Therefore, I maintain that the mode of interaction in the Residence Agreement negotiations was a bottom up diffusion process that allowed the regionalization of domestic policies.

Resumen Este artículo ofrece una explicación complementaria a la teoría de la difusión que se centra en el proceso de emergencia de la gobernanza desde una perspectiva de arriba hacia abajo (top-down). Esta explicación complementaria analiza los procesos de abajo hacia arriba (bottom-up) de difusión y los prueba mediante el estudio de la formulación de políticas en el Acuerdo de Residencia del Mercosur, firmado en el 2002. En base a entrevistas con actores clave, documentos y literatura académica, este artículo concluye que el Acuerdo fue principalmente el resultado de las negociaciones brasileñas y argentinas. Brasil necesitaba impulsar la cooperación regional después de la crisis del Mercosur y consideró que una amnistía migratoria conjunta podría tener un impacto positivo en la imagen del bloque. Sin embargo, la experiencia argentina en temas de migración permitió una política más coherente en la materia. Por lo tanto, se sostiene que el modo de interacción en las negociaciones del Acuerdo fue un proceso de difusión de abajo hacia arriba (bottom-up) que posibilitó la regionalización de las políticas domésticas.

Resumo Este artigo oferece uma explicação complementar à teoria da difusão que explica o processo de surgimento da governança regional a partir de uma perspectiva de cima para baixo (top-down). Essa explicação complementar analisa os processos de difusão de baixo para cima (bottom-up), e os testa por meio do estudo da formulação de políticas no Acordo de Residência do Mercosul, assinado em 2002. Tomando em consideração entrevistas com atores destacados, documentos e literatura acadêmica, este artigo conclui que o Acordo foi principalmente o resultado das negociações brasileiras e argentinas. O Brasil em um primeiro momento considerou uma anistia migratória regional para melhorar a imagem do Mercosul. No entanto, a experiência argentina em questões de migração permitiu uma política mais coerente na matéria. Portanto, este trabalho conclui que o modo de interação na negociação do Acordo foi um processo de difusão de baixo para cima (bottom-up) que produziu a regionalização de políticas domésticas.

Desviación paroxística de la mirada hacia arriba: estudio de caso / Paroxysmal upgaze deviation: case report / Desvio paroxístico do olhar para cima: estudo de caso

La desviación paroxística de la mirada hacia arriba es un síndrome infantil descrito por primera vez en 1988 y desde entonces solo se registran alrededor de cincuenta reportes en el mundo. Su etiología no es clara y, aunque su pronóstico es variable, la mayoría de los informes señalan que durante el crecimiento los episodios tienden a disminuir en frecuencia y duración hasta desaparecer. El caso que se reporta corresponde a un niño de 16 meses de edad, quien desde los 11 meses presenta episodios de supraversión sostenida de la mirada conjugada de duración variable con flexión cervical compensatoria y nistagmo vertical a la fijación ocular sin alteración del estado de conciencia. Los episodios son de predominio matinal y se exacerban por situaciones de estrés como el ayuno o el insomnio; sin embargo, ceden con la conciliación del sueño. Los exámenes neurológico y oftalmológico resultan normales y a su vez las neuroimágenes y electroencefalograma no tienen hallazgos relevantes.

The paroxysmal upgaze deviation is a syndrome that described in infants for first time in 1988; there are just about 50 case reports worldwide ever since. Its etiology is unclear and though it prognosis is variable; most case reports indicate that during growth the episodes tend to decrease in frequency and duration until they disappear. It describes a 16-months old male child who since 11-months old presented many episodes of variable conjugate upward deviation of the eyes, compensatory neck flexion and down-beat saccades in attempted downgaze. These events are predominantly diurnal, and are exacerbated by stressful situations such as fasting or insomnia, however and improve with sleep. They have normal neurologic and ophthalmologic examination, and neuroimaging and EEG findings are not relevant.

O desvio paroxístico do olhar para cima é um síndrome infantil foi descrito por primeira vez no ano 1988 e desde então só se registram cerca de cinquenta reportes no mundo. Sua etiologia não é clara e, mesmo que seu prognóstico é variável, a maioria dos informes assinalam que durante o crescimento, os episódios tendem a diminuir em frequência e duração até desaparecer. O caso que é reportado corresponde a uma criança de 16 meses de idade, que desde os 11 meses, apresenta episódios de supraversão sustentada do olhar conjugado de duração variável com flexão cervical compensatória e nistagmo vertical à fixação ocular sem alteração do estado de consciência. Os episódios são de predomínio matinal e se exacerbam por situações de estresse como o jejum ou a insônia; no entanto, cedem com a conciliação do sono. Os exames neurológico e oftalmológico resultam normais e a sua vez as neuroimagens e electroencefalograma não têm resultados relevantes.