Models based on ordinary differential equations (ODE) are widespread tools for describing dynamical systems. In biomedical sciences, data from each subject can be sparse making difficult to precisely estimate individual parameters by standard non-linear regression but information can often be gained from between-subjects variability. This makes natural the use of mixed-effects models to estimate population parameters. Although the maximum likelihood approach is a valuable option, identifiability issues favour Bayesian approaches which can incorporate prior knowledge in a flexible way. However, the combination of difficulties coming from the ODE system and from the presence of random effects raises a major numerical challenge. Computations can be simplified by making a normal approximation of the posterior to find the maximum of the posterior distribution (MAP). Here we present the NIMROD program (normal approximation inference in models with random effects based on ordinary differential equations) devoted to the MAP estimation in ODE models. We describe the specific implemented features such as convergence criteria and an approximation of the leave-one-out cross-validation to assess the model quality of fit. In pharmacokinetics models, first, we evaluate the properties of this algorithm and compare it with FOCE and MCMC algorithms in simulations. Then, we illustrate NIMROD use on Amprenavir pharmacokinetics data from the PUZZLE clinical trial in HIV infected patients.

• MeSH
• Algorithms MeSH
• Bayes Theorem MeSH
• HIV Infections drug therapy   MeSH
• Carbamates pharmacokinetics   MeSH
• Clinical Trials as Topic MeSH
• Anti-HIV Agents pharmacokinetics   MeSH
• Humans MeSH
• Drug Monitoring instrumentation   methods   MeSH
• Likelihood Functions MeSH
• Reproducibility of Results MeSH
• Software * MeSH
• Models, Statistical MeSH
• Sulfonamides pharmacokinetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Sparse, incomplete and inappropriate historical records of invasive species often hamper invasive species management interventions. Population genetic analyses of invaders might provide a suitable context for the identification of their source populations and possible introduction routes. Here, we describe the population genetics of Heracleum persicum Desf. ex Fisch and trace its route of introduction into Europe. Microsatellite markers revealed a significantly higher genetic diversity of H. persicum in its native range, and the loss of diversity in the introduced range may be attributed to a recent genetic bottleneck. Bayesian cluster analysis on regional levels identified three and two genetic clusters in the native and the introduced ranges, respectively. A global structure analysis revealed two worldwide distinct genetic groups: one primarily in Iran and Denmark, the other primarily in Norway. There were also varying degrees of admixture in England, Sweden, Finland and Latvia. Approximate Bayesian computation indicated two independent introductions of H. persicum from Iran to Europe: the first one in Denmark and the second one in England. Finland was subsequently colonized by English populations. In contrast to the contemporary hypothesis of English origin of Norwegian populations, we found Finland to be a more likely source for Norwegian populations, a scenario supported by higher estimated historical migration from Finland to Norway. Genetic diversity per se is not a primary determinant of invasiveness in H. persicum. Our results indicate that, due to either pre-adaptations or rapid local adaptations, introduced populations may have acquired invasiveness after subsequent introductions, once a suitable environment was encountered.

• MeSH
• Bayes Theorem MeSH
• Heracleum genetics   MeSH
• DNA, Plant genetics   MeSH
• Genetic Variation * MeSH
• Genotype MeSH
• Microsatellite Repeats MeSH
• Genetics, Population * MeSH
• Sequence Analysis, DNA MeSH
• Cluster Analysis MeSH
• Linkage Disequilibrium MeSH
• Introduced Species * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

The crucial steps in biological invasions, related to the shaping of genetic architecture and the current evolution of adaptations to a novel environment, usually occur in small populations during the phases of introduction and establishment. However, these processes are difficult to track in nature due to invasion lag, large geographic and temporal scales compared with human observation capabilities, the frequent depletion of genetic variance, admixture and other phenomena. In this study, we compared genetic and historical evidence related to the invasion of the West European hedgehog to New Zealand to infer details about the introduction and establishment. Historical information indicates that the species was initially established on the South Island. A molecular assay of populations from Great Britain and New Zealand using mitochondrial sequences and nuclear microsatellite loci was performed based on a set of analyses including approximate Bayesian computation, a powerful approach for disentangling complex population demographies. According to these analyses, the population of the North Island was most similar to that of the native area and showed greatest reduction in genetic variation caused by founder demography and/or drift. This evidence indicated the location of the establishment phase. The hypothesis was corroborated by data on climate and urbanization. We discuss the contrasting results obtained by the molecular and historical approaches in the light of their different explanatory power and the possible biases influencing the description of particular aspects of invasions, and we advocate the integration of the two types of approaches in invasion biology.

• MeSH
• Bayes Theorem MeSH
• Population Density MeSH
• Hedgehogs genetics   physiology   MeSH
• Humans MeSH
• Microsatellite Repeats genetics   MeSH
• DNA, Mitochondrial genetics   MeSH
• Molecular Sequence Data MeSH
• Genetics, Population * MeSH
• Introduced Species MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• New Zealand MeSH

Oceanic islands have been a test ground for evolutionary theory, but here, we focus on the possibilities for evolutionary study created by offshore islands. These can be colonized through various means and by a wide range of species, including those with low dispersal capabilities. We use morphology, modern and ancient sequences of cytochrome b (cytb) and microsatellite genotypes to examine colonization history and evolutionary change associated with occupation of the Orkney archipelago by the common vole (Microtus arvalis), a species found in continental Europe but not in Britain. Among possible colonization scenarios, our results are most consistent with human introduction at least 5100 bp (confirmed by radiocarbon dating). We used approximate Bayesian computation of population history to infer the coast of Belgium as the possible source and estimated the evolutionary timescale using a Bayesian coalescent approach. We showed substantial morphological divergence of the island populations, including a size increase presumably driven by selection and reduced microsatellite variation likely reflecting founder events and genetic drift. More surprisingly, our results suggest that a recent and widespread cytb replacement event in the continental source area purged cytb variation there, whereas the ancestral diversity is largely retained in the colonized islands as a genetic 'ark'. The replacement event in the continental M. arvalis was probably triggered by anthropogenic causes (land-use change). Our studies illustrate that small offshore islands can act as field laboratories for studying various evolutionary processes over relatively short timescales, informing about the mainland source area as well as the island.

• MeSH
• Arvicolinae anatomy & histology   genetics   MeSH
• Bayes Theorem MeSH
• Biological Evolution * MeSH
• Cytochromes b genetics   MeSH
• Phylogeny MeSH
• Microsatellite Repeats MeSH
• DNA, Mitochondrial genetics   MeSH
• Molecular Sequence Data MeSH
• Islands * MeSH
• Genetics, Population * MeSH
• Animal Distribution MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Belgium MeSH
• Islands * MeSH
• United Kingdom MeSH

Lecanosticta acicola is a heterothallic ascomycete that causes brown spot needle blight on native and nonnative Pinus spp. in many regions of the world. In this study we investigated the origin of European L. acicola populations and estimated the level of random mating of the pathogen in affected areas. Part of the elongation factor 1-α gene was sequenced, 11 microsatellite regions were screened, and the mating type idiomorphs were determined for 201 isolates of L. acicola collected from three continents and 17 host species. The isolates from Mexico and Guatemala were unique, highly diverse and could represent cryptic species of Lecanosticta. The isolates from East Asia formed a uniform and discrete group. Two distinct populations were identified in both North America and Europe. Approximate Bayesian computation analyses strongly suggest independent introductions of two populations from North America into Europe. Microsatellite data and mating type distributions indicated random recombination in the populations of North America and Europe. Its intercontinental introduction can most likely be explained as a consequence of the movement of infected plant material. In contrast, the spread of L. acicola within Europe appears to be primarily due to conidial dispersion and probably also ascospore dissemination.

• MeSH
• Ascomycota genetics   isolation & purification   physiology   MeSH
• Bayes Theorem MeSH
• Pinus microbiology   MeSH
• Genes, Mating Type, Fungal genetics   MeSH
• Phylogeny MeSH
• Genetic Variation MeSH
• Plant Leaves microbiology   MeSH
• Microsatellite Repeats genetics   MeSH
• Plant Diseases microbiology   MeSH
• Genetics, Population MeSH
• Geography MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH
• Guatemala MeSH
• Mexico MeSH
• North America MeSH

The book was written as a necessity to gather knowledge from different domains of Medical Informatics. Nakladatelská anotace. Kráceno

• MeSH
• Medical Informatics MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• lékařská informatika

Current species distributions at high latitudes are the product of expansion from glacial refugia into previously uninhabitable areas at the end of the last glaciation. The traditional view of postglacial colonization is that southern populations expanded their ranges into unoccupied northern territories. Recent findings on mitochondrial DNA (mtDNA) of British small mammals have challenged this simple colonization scenario by demonstrating a more complex genetic turnover in Britain during the Pleistocene-Holocene transition where one mtDNA clade of each species was replaced by another mtDNA clade of the same species. Here, we provide evidence from one of those small mammals, the bank vole (Clethrionomys glareolus), that the replacement was genome-wide. Using more than 10 000 autosomal SNPs we found that similar to mtDNA, bank vole genomes in Britain form two (north and south) clusters which admix. Therefore, the genome of the original postglacial colonists (the northern cluster) was probably replaced by another wave of migration from a different continental European population (the southern cluster), and we gained support for this by modelling with approximate Bayesian computation. This finding emphasizes the importance of analysis of genome-wide diversity within species under changing climate in creating opportunities for sophisticated testing of population history scenarios.

• MeSH
• Arvicolinae genetics   physiology   MeSH
• Phylogeny MeSH
• Genome * MeSH
• Polymorphism, Single Nucleotide * MeSH
• Animal Migration * MeSH
• Animal Distribution * MeSH
• Sequence Analysis, DNA MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• England MeSH
• Scotland MeSH
• Wales MeSH

• MeSH
• Information Systems MeSH
• Medical Informatics MeSH
• Medicine MeSH
• Publication type
• Congress MeSH
• Collected Work MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• lékařská informatika