metasim 1.0: an individual‐based environment for simulating population genetics of complex population dynamics

metasim provides a flexible environment in which to perform individual‐based population genetic simulations. A wide range of landscape‐level dynamics, population structures, and within‐population demographies can be represented using the framework implemented in this software. In addition, temporal variation in all demographic characteristics can be simulated, both deterministically and stochastically. Such simulations can be used to produce null distributions of genotypes under realistic conditions. These genotypic data can then be used by a variety of analytical programs to develop null expectations of any population genetic statistic estimated from genotypic data.     

Facial skeletal changes following hypertelorbitism correction

This is a retrospective study of skeletal changes in 19 patients with corrected hypertelorism. A favorable outcome, defined as relapse less than 5 mm, occurred in patients with an average interorbital distance of 32 mm, whereas patients with an average interorbital distance of 40 mm tended to relapse over 5 mm. Neither age, interorbital configuration, nor diagnosis affected the stability of orbital translocation. At last evaluation (mean 6.7 years postoperatively), the mean interorbital distance was 22.4 mm in the favorable outcome group and 28.3 mm in the unfavorable category. This study suggested that the standard hypertelorism operation may interfere with anterior facial growth. Unless psychosocial factors predominate in a child with mild deformity, repair should be postponed until late adolescence. In a young child with gross telorbitism, nasoethmoidal resection and transmaxillary osteotomies or facial bipartition is justified. Another long-term skeletal problem was resorption of the reconstructed nasal complex. Technical and biological explanations for this are given. The correction of hypertelorism is surgery of the nose and of the midface.     

Secukinumab provides sustained PASDAS-defined remission in psoriatic arthritis and improves health-related quality of life in patients achieving remission: 2-year results from the phase III FUTURE 2 study

Background

Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2?years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2?years among patients with PsA in the FUTURE 2 study.

Methods

PASDAS (cut-off scores: remission ≤?1.9; LDA >?1.9 and?<?3.2; Moderate Disease Activity ≥?3.2 and?<?5.4; and high disease activity [HDA]?≥?5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150?mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures.

Results

In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300?mg and in 15.2% and 19.2%, respectively, in the secukinumab 150?mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission?+?LDA at week 16 with secukinumab 300 and 150?mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2?years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2?years.

Conclusions

Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2?years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA.

Trial registration

ClinicalTrials.gov, NCT01752634. Registered on December 19, 2012.EUDRACT, 2012-004439-22. Registered on December 12, 2012.

     

Biological Expression of Antigenic Determinants of Murine Leukemia Virus Proteins gp69/71 and p30

Antisera to purified structural proteins of Rauscher murine leukemia virus, the major envelope glycoprotein, gp69/71, and the major internal protein, p30, were studied by immunofluorescence of viable and fixed virus-infected cells and by virus neutralization. Group-specific and type-specific determinants of gp69/71 were demonstrated by immunofluorescence and virus neutralization tests, indicating that these determinants are located in the cytoplasm and probably on the cell surface as well as on virus envelope. Antisera against p30 showed anti-group and anti-interspecies activities by immunofluorescence with no virus-neutralizing activity. Both antigenic determinants of gp69/71 were sensitive to guanidine-hydrochloride and to a lesser degree to ether treatment, whereas the group-specific determinants of p30 were relatively stable to these treatments.     

A first report on coexistence and hybridization of <Emphasis Type="Italic">Mytilus trossulus</Emphasis> and <Emphasis Type="Italic">M. edulis</Emphasis> mussels in Greenland

Semi-sessile Mytilus mussels are used as indicators of climate changes, but their geographic distribution is not sufficiently known in the Arctic. The aim of this study was to investigate the taxonomic status and genetic differentiation of Mytilus populations in a Northwest Greenlandic fjord at Maarmorilik, impacted by contaminations from a former mine. In this study, mussels were collected at three sites differing in exposure to environmental factors. A total of 54 polymorphic SNPs found in the Mytilus EST and DNA sequences analyzed were successfully applied to 256 individuals. The results provided the first evidence for the existence of M. trossulus in Greenland. The mussel from M. trossulus and M. edulis taxa are shown to coexist and hybridize in the fjord. The three studied sites were found to differ significantly in the distribution of taxa with a higher prevalence of M. trossulus in the inner fjord. The identified M. edulis × M. trossulus hybrids mostly had a hybrid index score of about 0.5, indicating a similar number of alleles characteristic for M. trossulus and M. edulis. There was a low number of backcrosses between ‘pure’ taxa and hybrids. This newly discovered hybrid zone between the two taxa is unique in comparison with the Canadian populations. As Mytilus mussels in Greenland hitherto have been regarded as the one taxon M. edulis, the results have importance for biogeography and future monitoring and environmental studies.