672 research outputs found
Mathematical modelling of clonal stem cell dynamics
No full textStudying cell fate dynamics is complicated by the fact that direct in vivo observation of individual cell fate outcomes is usually not possible and only multicellular data of cell clones can be obtained. In this situation, experimental data alone is not sufficient to validate biological models because the hypotheses and the data cannot be directly compared and thus standard statistical tests cannot be leveraged. On the other hand, mathematical modelling can bridge the scales between a hypothesis and measured data via quantitative predictions from a mathematical model. Here, we describe how to implement the rules behind a hypothesis (cell fate outcomes) one-to-one as a stochastic model, how to evaluate such a rule-based model mathematically via analytical calculation or stochastic simulations of the model's Master equation, and to predict the outcomes of clonal statistics for respective hypotheses. We also illustrate two approaches to compare these predictions directly with the clonal data to assess the models.</p
Active transport and cluster formation on 2D networks
No full textWe introduce a model for active transport on inhomogeneous networks embedded in a diffusive environment which is motivated by vesicular transport on actin filaments. In the presence of a hard- core interaction, particle clusters are observed that exhibit an algebraically decaying distribution in a large parameter regime, indicating the existence of clusters on all scales. The scale-free behavior can be understood by a mechanism promoting preferential attachment of particles to large clusters. The results are compared with a diffusion-limited aggregation model and active transport on a regular network. For both models we observe aggregation of particles to clusters which are characterized by a finite size scale if the relevant time scales and particle densities are considered
Skeletal age assessment in black African children in Kenya: Applicability of the Greulich and Pyle method
No full textBackground: One of the most popular methods used for skeletal age assessment is Greulich and Pyle method which was based on a study done in the 1940s on growth and development in Caucasian North American children.
Objective: This study aimed to determine the applicability of Greulich and Pyle standards in assessment of skeletal age in black African children living in Kenya.
Materials and Methods: 110 participants referred for hand and wrist radiographs for evaluation of trauma at Kenyatta National Hospital from January 2017 to December 2017 study period, were included in the study. Chronological age was calculated using the participants’ date of birth. Skeletal age was determined according to the Greulich and Pyle method by three independent investigators who were blinded to the chronological age. Statistical analyses were performed to determine mean differences between chronological age and skeletal age in boys and girls and inter-rater variability.
Results: No statistically significant difference was found between skeletal ages estimated by the 3 observers. (p =0.409) Overall in girls, skeletal age was underestimated compared to chronological age with differences from 2 to 16 months (mean difference =12months) found between estimated skeletal age and chronological age. In boys, skeletal age was underestimated by 4 to 14 months (mean difference =11months) overall compared to chronological age.
Conclusion: The results suggest black African children may have different skeletal development compared to American children from who the Greulich and Pyle atlas was derived and thus it should be used cautiously in age assessment in black African children
Homeostatic regulation of renewing tissue cell populations via crowding control: stability, robustness and quasi-dedifferentiation
No full textTo maintain renewing epithelial tissues in a healthy, homeostatic state, cell divisions and differentiation need to be tightly regulated. Mechanisms of homeostatic regulation often rely on crowding feedback control: cells are able to sense the cell density in their environment, via various molecular and mechanosensing pathways, and respond by adjusting division, differentiation, and cell state transitions appropriately. Here, we determine, via a mathematically rigorous framework, which general conditions for the crowding feedback regulation (i) must be minimally met, and (ii) are sufficient, to allow the maintenance of homeostasis in renewing tissues. We show that those conditions naturally allow for a degree of robustness toward disruption of regulation. Furthermore, intrinsic to this feedback regulation is that stem cell identity is established collectively by the cell population, not by individual cells, which implies the possibility of ‘quasi-dedifferentiation’, in which cells committed to differentiation may reacquire stem cell properties upon depletion of the stem cell pool. These findings can guide future experimental campaigns to identify specific crowding feedback mechanisms.</p
Universality of clonal dynamics poses fundamental limits to identify stem cell self-renewal strategies
No full textHow adult stem cells maintain self-renewing tissues is in vivo commonly assessed by analysing clonal data from cell lineage tracing assays. To identify strategies of stem cell self-renewal requires that different models of stem cell fate choice predict sufficiently different clonal statistics. Here we show that models of cell fate choice can, in homeostatic tissues, be categorized by exactly two ‘universality classes’, whereby models of the same class predict, under asymptotic conditions, the same clonal statistics. Those classes relate to generalizations of the canonical asymmetric vs. symmetric stem cell self-renewal strategies and are distinguished by a conservation law. This poses both challenges and opportunities to identify stem cell self-renewal strategies: while under asymptotic conditions, self-renewal models of the same universality class cannot be distinguished by clonal data only, models of different classes can be distinguished by simple means.</p
Is the Greulich and Pyle atlas still valid for Dutch Caucasian children today?
No full textIn our Paediatric Radiology Department, the Greulich and Pyle technique is used to assess skeletal age. Several authors have raised questions with regard to the applicability of this technique in a contemporary paediatric and adolescent population. To compare skeletal age and calendar age in a healthy Dutch Caucasian population in order to test the applicability in this specific population. For this study we enrolled 278 Dutch Caucasian boys (age range 5.0-19.5 years, mean 12.6 years) and 294 Dutch Caucasian girls (age range 5.2-19.9 years, mean 12.2 years). Radiographs of the left hand were scored according to the Greulich and Pyle atlas by two investigators. Intra-observer coefficient of variation of duplicate assessment of skeletal age for investigator 1 (resident) was 2.4 % and for investigator 2 (radiologist) was 1.5 %. We found no significant systematic differences between the two observers regarding variability and levels of measurement, and the agreement was good. There was a strongly significant correlation between skeletal and calendar age rgirls = 0.974 and rboys = 0.979 (P < 0.001). On average, calendar age preceded skeletal age by a small amount (1.7 months in girls and 3.3 months in boys, both P < 0.001). The reliability of the Greulich and Pyle atlas in our study corresponds well with previously reported studies. Based on our data, we conclude that the Greulich and Pyle atlas is still applicable in Dutch Caucasian children and adolescent
De Greulich&Pyle-atlas voor het bepalen van de skeletleeftijd nog steeds bruikbaar in een hedendaagse Nederlandse blanke populatie
No full textObjective. To validate the use of the Greulich&Pyle atlas for determining skeletal age in a healthy contemporary Dutch white population. Design. Diagnostic evaluation study. Methods. In 278 Dutch white boys (mean age: 12.6 years; range: 5.0-19.5), and 294 Dutch white girls (mean age: 12.2 years; range: 5.2-19.9) radiographs of the left hand were scored by two investigators according to the Greulich&Pyle atlas. Participants and their parents or guardians gave informed consent. Results. The intra-observer coefficient of variation of duplicate assessment of skeletal age for the investigators was 2.4% and 1.5% respectively. There were no significant systematic differences between both observers with respect to variability and the agreement between the two was good. There was a strong significant correlation between skeletal and calendar age: rgirls = 0.974 and rboys = 0-979 (both p < 0.001). On average calendar age slightly preceded skeletal age by 1.7 months in girls and 3.3 months in boys (both p < 0.001). Conclusion. The Greulich&Pyle atlas still appears to be applicable in a contemporary Dutch white population
The Neural basis of free language choice in bilingual speakers: disentangling language choice and language execution
No full textFor everyday communication, bilingual speakers need to face the complex task of rapidly choosing the most appropriate language given the context, maintaining this choice over the current communicative act, and shielding lexical selection from competing alternatives from non-target languages. Yet, speech production of bilinguals is typically flawless and fluent. Most of the studies available to date constrain speakers' language choice by cueing the target language and conflate language choice with language use. This left largely unexplored the neural mechanisms underlying free language choice, i.e., the voluntary situation of choosing the language to speak. In this study, we used fMRI and Multivariate Pattern Analysis to identify brain regions encoding the target language when bilinguals are free to choose in which language to name pictures. We found that the medial prefrontal cortex encoded the chosen language prior to speaking. By contrast, during language use, language control recruited a wider brain network including the left inferior frontal lobe, the basal ganglia, and the angular and inferior parietal gyrus bilaterally. None of these regions were involved in language choice. We argue that the control processes involved in language choice are different from those involved in language use. Furthermore, our findings confirm that the medial prefrontal cortex is a domain-general region critical for free choice and that bilingual language choice relies on domain general processes.CR and SSA were supported by the PRIN grant 2010RP5RNM_001 from the Italian Ministry of University; AC was supported by two grants from the Spanish Government, PSI2011-23033, PSI2014-52181-P, a grant from the Catalan government (AGAUR SGR 268), and a grant from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007–2013 Cooperation grant agreement nº 613465 - AThEME)
Comparação entre métodos de estimativa da idade óssea: Greulich & Pyle, Eklöf & Ringertz e atlas digital de Gilsanz & Ratib
No full textThe current research aimed at evaluating the skeletal age, by means of hand and wrist radiographies, using the methods Greulich & Pyle (G&P) (1959), Eklöf & Ringertz (E&R) (1967) and the Gilsanz & Ratib digital atlas (G&R) (2005). The ages obtained from the three methods were compared, and the degree of concordance among them was determined. In order to accomplish these goals, a sample of 80 children was analyzed, 40 of the masculine gender and 40 of the feminine gender, varying from 7 to 15 years-old. All the radiographies of the individuals in the sample were digitized. Concerning the Greulich & Pyle method, an inspection evaluation of the images in the sample was carried out, comparing those images with the radiographies found at the standard atlas (“Radiographic atlas of skeletal development of the hand and wrist”), following the authors' instructions. For Eklöf & Ringertz method, the linear measures were carried out through the program Image Tool and, subsequently, the results were compared with the rates supposed by the authors. Referring to Gilsanz & Ratib method, the digitized images were compared with the images of the authors' digital atlas. Throughout the results, it was possible to realize that there was no expressive difference for the results between the methods Greulich & Pyle and Eklöf & Ringertz, not even for those between the methods Greulich & Pyle and Gilsanz & Ratib. Otherwise, when the rates obtained between the methods Eklöf & Ringertz and Gilsanz & Ratib were compared, statistically expressive differences were observed. In the genre comparison, important differences between the methods used were not noticed. Comparing the three methods concerning valuation of the bone age, Eklöf & Ringertz method presented the highest compatibility with the chronological age of the sample analyzed and Gilsanz & Ratib method presented the lowest one.A presente pesquisa teve como objetivo avaliar a idade esquelética, por meio de radiografias de mão e punho, utilizando os métodos de Greulich & Pyle (G&P) (1959), Eklöf & Ringertz (E&R) (1967) e o atlas digital de Gilsanz & Ratib (G&R) (2005). Foram feitas comparações das idades obtidas pelos três métodos, e determinado o grau de concordância entre eles. Para isto, analisou-se uma amostra de 80 crianças, 40 do gênero masculino e 40 do gênero feminino, com idades entre 7 e 15 anos. Todas as radiografias dos indivíduos da amostra foram digitalizadas. Para o método de Greulich & Pyle foi realizada uma avaliação inspecional das imagens da amostra, comparando-as com as radiografias encontradas no atlas padrão (“Radiographic atlas of skeletal development of the hand and wrist”), conforme o preconizado pelos autores. Para o método de Eklöf & Ringertz as medidas lineares foram feitas através do programa Image Tool e, posteriormente, seus resultados foram comparados com os valores preconizados pelos autores. Para o método de Gilsanz & Ratib as imagens digitalizadas foram comparadas com as imagens contidas no atlas digital dos respectivos autores. Através dos resultados, verificou-se que não existiu diferença significativa para os escores entre os métodos Greulich & Pyle e Eklöf & Ringertz, nem entre os métodos Greulich & Pyle e Gilsanz & Ratib. Já, quando foram comparados os valores obtidos entre os métodos Eklöf & Ringertz e Gilsanz & Ratib, observaram-se diferenças estatisticamente significantes. Na comparação entre os gêneros não foram encontradas diferenças relevantes entre os métodos utilizados. Na comparação dos três métodos para a estimativa da idade óssea, o que apresentou a maior compatibilidade com a idade cronológica da amostra estudada foi o de Eklöf & Ringertz, e a menor foi para o método de Gilsanz & Ratib
Statistical Properties of Disordered Driven Lattice Gases with Open Boundaries
No full textWe investigate driven lattice gases with open boundary conditions in presence of randomly distributed defect sites with reduced hopping rate 1. These systems can be used as models for intracellular transport systems impurified by immobile blocking molecules. In contrast to equilibrium, even macroscopic quantities in disordered non-equilibrium systems depend sensitively on the defect sample. We show that the leading behaviour in the disordered system is determined by the longest stretch of consecutive defect sites. Using results from extreme value statistics 2 this single-bottleneck approximation gives accurate results for the expectation values of the maximum current at small defect densities. Corrections from bottleneck interactions can be taken into account systematically by a perturbative expansion
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