The effects of lead time and visual aids in TTO valuation: a study of the EQ-VT framework

__Abstract__ __Background__ The effect of lead time in time trade-off (TTO) valuation is not well understood. The purpose of this study was to investigate the effects on health-state valuation of the length of lead time and the way the lead-time TTO task is displayed visually. __Methods__ Using two general population samples, we compared three lead-time TTO variants: 10 years of lead time in full health preceding 5 years of unhealthy time (standard); 5 years of lead time preceding 5 years of unhealthy time (experimental); and 10 years of lead time and 5 years of unhealthy time, presented with a visual aid to highlight the point where the lead time ends (experimental). Participants were randomized to receive one of the lead-time variants, as administered by a computer software program. __Results__ Health-state values generated by TTO valuation tasks using a longer lead time were slightly lower than those generated by tasks using a shorter lead time. When lead time and unhealthy time were presented with visual aids highlighting the difference between the lead time and unhealthy time, respondents spent more time considering health states with a value close to 0. __Conclusions__ Different lead-time time trade-off variants should be carefully studied in order to achieve the best measurement of health-state values using this new method

Gamma-rays from millisecond pulsars in Globular Clusters

Globular clusters (GCs) with their ages of the order of several billion years contain many final products of evolution of stars such as: neutron stars, white dwarfs and probably also black holes. These compact objects can be at present responsible for the acceleration of particles to relativistic energies. Therefore, gamma-ray emission is expected from GCs as a result of radiation processes occurring either in the inner magnetosperes of millisecond pulsars or in the vicinity of accreting neutron stars and white dwarfs or as a result of interaction of particles leaving the compact objects with the strong radiation field within the GC. Recently, GeV gamma-ray emission has been detected from several GCs by the new satellite observatory Fermi. Also Cherenkov telescopes reported interesting upper limits at the TeV energies which start to constrain the content of GCs. We review the results of these gamma-ray observations in the context of recent scenarios for their origin.Comment: 20 pages, 9 figures, will be published in Astrophysics and Space Science Series (Springer), eds. N. Rea and D.F. Torre

Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease

Pedigree, linkage and association studies are consistent with heritable variation for complex disease due to the segregation of genetic factors in families and in the population. In contrast, de novo mutations make only minor contributions to heritability estimates for complex traits. Nonetheless, some de novo variants are known to be important in disease etiology. The identification of risk-conferring de novo variants will contribute to the discovery of etiologically relevant genes and pathways and may help in genetic counseling. There is considerable interest in the role of such mutations in complex neuropsychiatric disease, largely driven by new genotyping and sequencing technologies. An important role for large de novo copy number variations has been established. Recently, whole-exome sequencing has been used to extend the investigation of de novo variation to point mutations in protein-coding regions. Here, we consider several challenges for the interpretation of such mutations in the context of their role in neuropsychiatric disease

Biview learning for human posture segmentation from 3D points cloud

Posture segmentation plays an essential role in human motion analysis. The state-of-the-art method extracts sufficiently high-dimensional features from 3D depth images for each 3D point and learns an efficient body part classifier. However, high-dimensional features are memory-consuming and difficult to handle on large-scale training dataset. In this paper, we propose an efficient two-stage dimension reduction scheme, termed biview learning, to encode two independent views which are depth-difference features (DDF) and relative position features (RPF). Biview learning explores the complementary property of DDF and RPF, and uses two stages to learn a compact yet comprehensive low-dimensional feature space for posture segmentation. In the first stage, discriminative locality alignment (DLA) is applied to the high-dimensional DDF to learn a discriminative low-dimensional representation. In the second stage, canonical correlation analysis (CCA) is used to explore the complementary property of RPF and the dimensionality reduced DDF. Finally, we train a support vector machine (SVM) over the output of CCA. We carefully validate the effectiveness of DLA and CCA utilized in the two-stage scheme on our 3D human points cloud dataset. Experimental results show that the proposed biview learning scheme significantly outperforms the state-of-the-art method for human posture segmentation. © 2014 Qiao et al

Hagfish and lamprey Hox genes reveal conservation of temporal colinearity in vertebrates

Hox genes exert fundamental roles for proper regional specification along the main rostro-caudal axis of animal embryos. They are generally expressed in restricted spatial domains according to their position in the cluster (spatial colinearity)—a feature that is conserved across bilaterians. In jawed vertebrates (gnathostomes), the position in the cluster also determines the onset of expression of Hox genes (a feature known as whole-cluster temporal colinearity (WTC)), while in invertebrates this phenomenon is displayed as a subcluster-level temporal colinearity. However, little is known about the expression profile of Hox genes in jawless vertebrates (cyclostomes); therefore, the evolutionary origin of WTC, as seen in gnathostomes, remains a mystery. Here, we show that Hox genes in cyclostomes are expressed according to WTC during development. We investigated the Hox repertoire and Hox gene expression profiles in three different species—a hagfish, a lamprey and a shark—encompassing the two major groups of vertebrates, and found that these are expressed following a whole-cluster, temporally staggered pattern, indicating that WTC has been conserved during the past 500 million years despite drastically different genome evolution and morphological outputs between jawless and jawed vertebrates

The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella

Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.Comment: 49 pages, 2 figures, 2 tables, 10 supplementary figures, 13 supplementary table

Statistical support for the hypothesis of developmental constraint in marsupial skull evolution.

Background: In contrast to placental neonates, in which all cranial bones are ossified, marsupial young have only the bones of the oral region and the exoccipital ossified at birth, in order to facilitate suckling at an early stage of development. In this study, we investigated whether this heterochronic shift in the timing of cranial ossification constrains cranial disparity in marsupials relative to placentals. Methods: We collected three-dimensional (3D) landmark data about the crania of a wide range of extant placentals and marsupials, and from six fossil metatherians (the clade including extant marsupials and their stem relatives), using a laser scanner and a 3D digitizer. Principal components analysis and delta variance tests were used to investigate the distribution and disparity of cranial morphology between different landmark sets (optimizing either number of landmarks or number of taxa) of the whole skull and of individual developmental or functional regions (neurocranium, viscerocranium, oral region) for extant placentals and marsupials. Marsupial and placental data was also compared based on shared ecological aspects including diet, habitat, and time of peak activity. Results: We found that the extant marsupial taxa investigated here occupy a much smaller area of morphospace than the placental taxa, with a significantly (P<0.01) smaller overall variance. Inclusion of fossil taxa did not significantly increase the variance of metatherian cranial shape. Fossil forms generally plotted close to or within the realm of their extant marsupial relatives. When the disparities of cranial regions were investigated separately, significant differences between placentals and marsupials were seen for the viscerocranial and oral regions, but not for the neurocranial region. Conclusion: These results support the hypothesis of developmental constraint limiting the evolution of the marsupial skull, and further suggest that the marsupial viscerocranium as a whole, rather than just the early-ossifying oral region, is developmentally constrained

Sex-Biased Expression of MicroRNAs in Schistosoma mansoni

Schistosomiasis is an important neglected tropical disease caused by digenean helminth parasites of the genus Schistosoma. Schistosomes are unusual in that they are dioecious and the adult worms live in the blood system. MicroRNAs play crucial roles during gene regulation and are likely to be important in sex differentiation in dioecious species. Here we characterize 112 microRNAs from adult Schistosoma mansoni individuals, including 84 novel microRNA families, and investigate the expression pattern in different sexes. By deep sequencing, we measured the relative expression levels of conserved and newly identified microRNAs between male and female samples. We observed that 13 microRNAs exhibited sex-biased expression, 10 of which are more abundant in females than in males. Sex chromosomes showed a paucity of female-biased genes, as predicted by theoretical evolutionary models. We propose that the recent emergence of separate sexes in Schistosoma had an effect on the chromosomal distribution and evolution of microRNAs, and that microRNAs are likely to participate in the sex differentiation/maintenance process

A study of the Z production cross-section in pp collisions at √s = 7 using tau final states

A measurement of the inclusive Z → ττ cross-section in pp collisions at √s =7 is presented based on a dataset of 1.0 fb[superscript −1] collected by the LHCb detector. Candidates for Z → τ τ decays are identified through reconstructed final states with two muons, a muon and an electron, a muon and a hadron, or an electron and a hadron. The production cross-section for Z bosons, with invariant mass between 60 and 120 GeV/c[superscript 2], which decay to τ leptons with transverse momenta greater than 20 GeV/c and pseudorapidities between 2.0 and 4.5, is measured to be σ[subscript pp]→Z→ττ = 71.4 ± 3.5 ± 2.8 ± 2.5 pb; the first uncertainty is statistical, the second is systematic, and the third is due to the uncertainty on the integrated luminosity. The ratio of the cross-sections for Z → τ τ to Z → μμ is determined to be 0.93 ± 0.09, where the uncertainty is the combination of statistical, systematic, and luminosity uncertainties of the two measurements.National Science Foundation (U.S.