Intravoxel incoherent motion diffusion-weighted imaging in the liver: comparison of mono-, bi- and tri-exponential modelling at 3.0-T.

PURPOSE: To determine whether a mono-, bi- or tri-exponential model best fits the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) signal of normal livers. MATERIALS AND METHODS: The pilot and validation studies were conducted in 38 and 36 patients with normal livers, respectively. The DWI sequence was performed using single-shot echoplanar imaging with 11 (pilot study) and 16 (validation study) b values. In each study, data from all patients were used to model the IVIM signal of normal liver. Diffusion coefficients (Di ± standard deviations) and their fractions (fi ± standard deviations) were determined from each model. The models were compared using the extra sum-of-squares test and information criteria. RESULTS: The tri-exponential model provided a better fit than both the bi- and mono-exponential models. The tri-exponential IVIM model determined three diffusion compartments: a slow (D1 = 1.35 ± 0.03 × 10(-3) mm(2)/s; f1 = 72.7 ± 0.9 %), a fast (D2 = 26.50 ± 2.49 × 10(-3) mm(2)/s; f2 = 13.7 ± 0.6 %) and a very fast (D3 = 404.00 ± 43.7 × 10(-3) mm(2)/s; f3 = 13.5 ± 0.8 %) diffusion compartment [results from the validation study]. The very fast compartment contributed to the IVIM signal only for b values ≤15 s/mm(2) CONCLUSION: The tri-exponential model provided the best fit for IVIM signal decay in the liver over the 0-800 s/mm(2) range. In IVIM analysis of normal liver, a third very fast (pseudo)diffusion component might be relevant. KEY POINTS: ? For normal liver, tri-exponential IVIM model might be superior to bi-exponential ? A very fast compartment (D = 404.00 ± 43.7 × 10 (-3)  mm (2) /s; f = 13.5 ± 0.8 %) is determined from the tri-exponential model ? The compartment contributes to the IVIM signal only for b ≤ 15 s/mm (2.)

Análisis de logs con soluciones Big Data e integración con BI corporativo

En este trabajo se hace una evaluación de la solución Big Data Hadoop como alternativa de almacenamiento y procesado de elevados volúmenes de datos en comparación con modelos relacionales tradicionales en un Enterprise Data Warehouse (EDW) corporativo, y de cómo ésta es capaz de integrarse con las herramientas de visualización típicas de las suites Business Intelligence.

From caging to rouse dynamics in polymer melts with intramolecular barriers: a critical test of the mode coupling theory

By means of computer simulations and solution of the equations of the mode coupling theory (MCT),we investigate the role of the intramolecular barriers on several dynamic aspects of nonentangled polymers. The investigated dynamic range extends from the caging regime characteristic of glass-formers to the relaxation of the chain Rouse modes. We review our recent work on this question,provide new results, and critically discuss the limitations of the theory. Solutions of the MCT for the structural relaxation reproduce qualitative trends of simulations for weak and moderate barriers. However, a progressive discrepancy is revealed as the limit of stiff chains is approached. This dis-agreement does not seem related with dynamic heterogeneities, which indeed are not enhanced by increasing barrier strength. It is not connected either with the breakdown of the convolution approximation for three-point static correlations, which retains its validity for stiff chains. These findings suggest the need of an improvement of the MCT equations for polymer melts. Concerning the relaxation of the chain degrees of freedom, MCT provides a microscopic basis for time scales from chain reorientation down to the caging regime. It rationalizes, from first principles, the observed deviations from the Rouse model on increasing the barrier strength. These include anomalous scaling of relaxation times, long-time plateaux, and nonmonotonous wavelength dependence of the mode correlators.

The role of intramolecular barriers on the glass transition of polymers: computer simulations versus mode coupling theory

We present computer simulations of a simple bead-spring model for polymer melts with intramolecular barriers. By systematically tuning the strength of the barriers, we investigate their role on the glass transition. Dynamic observables are analyzed within the framework of the mode coupling theory (MCT). Critical nonergodicity parameters, critical temperatures, and dynamic exponents are obtained from consistent fits of simulation data to MCT asymptotic laws. The so-obtained MCT λ-exponent increases from standard values for fully flexible chains to values close to the upper limit for stiff chains. In analogy with systems exhibiting higher-order MCT transitions, we suggest that the observed large λ-values arise form the interplay between two distinct mechanisms for dynamic arrest: general packing effects and polymer-specific intramolecular barriers. We compare simulation results with numerical solutions of the MCT equations for polymer systems, within the polymer reference interaction site model (PRISM) for static correlations. We verify that the approximations introduced by the PRISM are fulfilled by simulations, with the same quality for all the range of investigated barrier strength. The numerical solutions reproduce the qualitative trends of simulations for the dependence of the nonergodicity parameters and critical temperatures on the barrier strength. In particular, the increase in the barrier strength at fixed density increases the localization length and the critical temperature. However the qualitative agreement between theory and simulation breaks in the limit of stiff chains. We discuss the possible origin of this feature.

Directional dominance on stature and cognition in diverse human populations.

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Classificação BI-RADS™: categorização de 4.968 mamografias

Seguindo o modelo adotado pelo Colégio Americano de Radiologia, utilizamos o método BI-RADS™ (Breast Imaging Reporting and Data System) numa análise regional retrospectiva de 4.968 mamogramas, para categorizar e avaliar a freqüência dos achados mamográficos, distribuindo-os nos diferentes grupos desta classificação. Das 4.968 mamografias foram laudadas 44,4% (n = 2.208) como negativas, 46,3% (n = 2.305) como achados mamográficos benignos, 7,5% (n = 374) como achados mamográficos provavelmente benignos, 0,98% (n = 49) como achados mamográficos suspeitos e 0,72% (n = 36) como achados mamográficos altamente suspeitos. O estudo também demonstra a importância da uniformização do laudo mamográfico, através da aplicação da classificação BI-RADS™, sobretudo como preditor de malignidade, bem como na avaliação da conduta a ser seguida.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

Cooperative motion of intrinsic and actuated semiflexible swimmers

We examine the phenomenon of hydrodynamic-induced cooperativity for pairs of flagellated micro-organism swimmers, of which spermatozoa cells are an example. We consider semiflexible swimmers, where inextensible filaments are driven by an internal intrinsic force and torque-free mechanism (intrinsic swimmers). The velocity gain for swimming cooperatively, which depends on both the geometry and the driving, develops as a result of the near-field coupling of bending and hydrodynamic stresses. We identify the regimes where hydrodynamic cooperativity is advantageous and quantify the change in efficiency. When the filaments' axes are parallel, hydrodynamic interaction induces a directional instability that causes semiflexible swimmers that profit from swimming together to move apart from each other. Biologically, this implies that flagella need to select different synchronized collective states and to compensate for directional instabilities (e.g., by binding) in order to profit from swimming together. By analyzing the cooperative motion of pairs of externally actuated filaments, we assess the impact that stress distribution along the filaments has on their collective displacements.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

Submissão às recomendações do BI-RADS™ por médicos e pacientes: análise preliminar de 3.000 exames realizados em uma clínica particular

O Breast Imaging Reporting and Data System (BI-RADS™) do American College of Radiology é um sistema que objetiva padronizar o laudo mamográfico, reduzir os fatores de confusão na descrição e interpretação das imagens e facilitar a emissão do resultado final do exame. OBJETIVO: Buscar identificar o grau de submissão das mulheres e médicos às recomendações do BI-RADS em Goiânia, GO. MATERIAIS E MÉTODOS: Foram avaliadas, prospectivamente, 3.000 mulheres submetidas à mamografia em um serviço radiológico particular em Goiânia (janeiro a dezembro de 2002). Os laudos foram emitidos de acordo com o BI-RADS. As mulheres classificadas nas categorias 0, 3, 4 e 5 foram acompanhadas por contato telefônico. RESULTADOS: Mulheres que se recusaram a seguir orientação: categorias 0 (11,5%), 3 (13,8%), 4 (28%) e 5 (0%). Não houve orientação médica para seguir recomendação: categorias 0 (18,2%), 3 (17%), 4 (20%). Mulheres que se submeteram à recomendação: categorias 0 (1,8%), 3 (5,7%), 4 (40%), 5 (100%). Perdidas no seguimento: categorias 0 (68,5%), 3 (39%) e 4 (12%). CONCLUSÃO: É baixa a submissão às recomendações do BI-RADS nas categorias 0 e 3, e moderada na categoria 4. Aproximadamente 30% das mulheres classificadas na categoria 0 não se submeteram à avaliação adicional por imagem, por recusa própria ou por falta de orientação médica.

Predição de malignidade em pacientes das categorias 4 e 5 BI-RADS™

Foi realizado estudo retrospectivo, de agosto de 1999 a junho de 2002, que selecionou 6.999 laudos mamográficos consecutivos que seguiram a padronização Breast Imaging Reporting and Data System (BI-RADS™). Neste estudo objetivamos uma análise regional de achados mamográficos categorias 4 e 5 BI-RADS, que foram recomendados a estudo histopatológico, avaliando a sensibilidade do método nessas categorias como indicador de malignidade. Foram laudados 43,65% (n = 3.055) como negativos, 47,36% (n = 3.315) como achados mamográficos benignos, 7,47% (n = 523) como achados mamográficos provavelmente benignos, 0,87% (n = 61) como achados mamográficos suspeitos e 0,64% (n = 45) como achados mamográficos altamente suspeitos. Das pacientes das categorias 4 (61 pacientes) e 5 (45 pacientes), todas encaminhadas à biópsia, foram obtidos resultados histopatológicos de 27 da categoria 4 (44,26%) e de 27 da categoria 5 (60%). Das pacientes da categoria 4, obteve-se 55,55% (n = 15) de lesões malignas, e das pacientes da categoria 5, obteve-se 96,29% (n = 26) de lesões malignas. O estudo mostra o alto valor preditivo positivo de malignidade da categoria 5 BI-RADS e a necessidade real de prosseguimento da investigação das mamografias categoria 4 BI-RADS.

Testing reciprocity in social interactions: A comparison between the Directional consistency and Skew symmetry statistics

In the present work we focus on two indices that quantify directionality and skew-symmetrical patterns in social interactions as measures of social reciprocity: the Directional consistency (DC) and Skew symmetry indices. Although both indices enable researchers to describe social groups, most studies require statistical inferential tests. The main aims of the present study are: firstly, to propose an overall statistical technique for testing null hypotheses regarding social reciprocity in behavioral studies, using the DC and Skew symmetry statistics (Φ) at group level; and secondly, to compare both statistics in order to allow researchers to choose the optimal measure depending on the conditions. In order to allow researchers to make statistical decisions, statistical significance for both statistics has been estimated by means of a Monte Carlo simulation. Furthermore, this study will enable researchers to choose the optimal observational conditions for carrying out their research, as the power of the statistical tests has been estimated.

Breast imaging reporting and data system (BI-RADS™): como tem sido utilizado?

O Breast Imaging Reporting and Data System (BI-RADS™), do American College of hRadiology, foi concebido para padronizar o laudo mamográfico e reduzir os fatores de confusão na descrição e interpretação das imagens, além de facilitar o monitoramento do resultado final. OBJETIVO: Identificar a maneira como vem sendo utilizado o BI-RADS™, gerando informações que possam auxiliar o Colégio Brasileiro de Radiologia a desenvolver estratégias para aperfeiçoar o seu uso. MATERIAIS E MÉTODOS: Os dados foram coletados na cidade de Goiânia, GO. Foram solicitados os exames de mamografia anteriores a todas as mulheres que se dirigiram ao serviço para realização de mamografia entre janeiro/2003 e junho/2003. Foram incluídos na análise exames anteriores, realizados entre 1/7/2001 e 30/6/2003. RESULTADOS: Foram coletados 104 laudos anteriores, emitidos por 40 radiologistas de 33 diferentes serviços. Dos 104 laudos, 77% (n = 80) utilizavam o BI-RADS™. Destes, apenas 15% (n = 12) eram concisos, nenhum utilizava a estrutura e organização recomendadas pelo sistema, 98,75% (n = 79) não respeitavam o léxico e 65% (n = 51) não faziam recomendação de conduta. CONCLUSÃO: O BI-RADS™, apesar de bastante utilizado, não foi reconhecido como sistema para padronização dos laudos. Foi usado quase exclusivamente como forma de classificação final dos exames.