“
“One of the central problems in mathematical genetics is the inference of evolutionary parameters of a population (such as the mutation rate) based on the observed genetic types in a finite DNA sample. If the population model under consideration is in the GDC-0973 purchase domain of attraction of the classical Fleming-Viot process, such as the Wright-Fisher- or the Moran model, then the standard means to describe its genealogy is Kingman’s coalescent. For this coalescent process, powerful inference methods are well-established. An important feature of the above class of

models is, roughly speaking, that the number of offspring of each individual is small when compared to the total population size, and hence all ancestral collisions are binary only. Recently, more general population models have been studied, in particular in the domain of attraction of so-called generalised Lambda-Fleming-Viot processes, as well as their (dual) genealogies, given by the so-called Lambda-coalescents, which allow multiple collisions. Moreover, Eldon and Wakeley (Genetics 172:2621-2633, 2006) provide evidence that such more general coalescents might actually be more adequate to describe real populations with extreme reproductive behaviour,

in particular many marine species. In this paper, we extend methods of Ethier and Griffiths (Ann Probab 15(2):515-545, 1987) and Griffiths and Tavare (Theor Pop Biol 46:131-159, 1994a, Stat Sci 9:307-319, 1994b, Philos Trans Roy Soc Lond Ser B 344:403-410, selleck chemicals llc 1994c, Math Biosci 12:77-98, 1995) to obtain a likelihood based inference method for general Lambda-coalescents. In particular, we obtain a method to compute (approximate) likelihood surfaces for the observed type probabilities of a given sample. We argue that within the selleck products (vast) family of Lambda-coalescents, the parametrisable sub-family of Beta(2-alpha, alpha)-coalescents, where alpha is an element

of (1, 2], are of particular relevance. We illustrate our method using simulated datasets, thus obtaining maximum-likelihood estimators of mutation and demographic parameters.”
“Background: We aimed to assess the impact of TDF/FTC +LPV/r-based HAART on the quality of immune reconstitution and on microbial translocation (MT) in HIV-infected antiretroviral-naive late presenting patients.\n\nMethods: 40 HIV+ antiretroviral-naive patients starting a first TDF/FTC+LPV/r HAART with CD4+<= 350 cell/mu L (20 “severe immune depression” patients -SID CD4+<= 100/mu L; 20 “moderate immune depression” patients -MID, CD4+ 200-350/mu L) were followed for 12 months (T12). CD38+CD8+, CD45R0+CD38+CD8+, CD95+CD4+/CD8+, CD127+CD4+/CD8+, pStat5 signalling (flow cytometry), plasma IL-7, sCD14 (ELISA), LPS (LAL) were tested at T0 and T12.\n\nResults: By T12, both study groups displayed significant CD4+ increase and HIV-RNA reduction (p<.01).