Probit models for capture-recapture data subject to imperfect detection, individual heterogeneity and misidentification

As noninvasive sampling techniques for animal populations have become more popular, there has been increasing interest in the development of capture-recapture models that can accommodate both imperfect detection and misidentification of individuals (e.g., due to genotyping error). However, current methods do not allow for individual variation in parameters, such as detection or survival probability. Here we develop misidentification models for capture-recapture data that can simultaneously account for temporal variation, behavioral effects and individual heterogeneity in parameters. To facilitate Bayesian inference using our approach, we extend standard probit regression techniques to latent multinomial models where the dimension and zeros of the response cannot be observed. We also present a novel Metropolis-Hastings within Gibbs algorithm for fitting these models using Markov chain Monte Carlo. Using closed population abundance models for illustration, we re-visit a DNA capture-recapture population study of black bears in Michigan, USA and find evidence of misidentification due to genotyping error, as well as temporal, behavioral and individual variation in detection probability. We also estimate a salamander population of known size from laboratory experiments evaluating the effectiveness of a marking technique commonly used for amphibians and fish. Our model was able to reliably estimate the size of this population and provided evidence of individual heterogeneity in misidentification probability that is attributable to variable mark quality. Our approach is more computationally demanding than previously proposed methods, but it provides the flexibility necessary for a much broader suite of models to be explored while properly accounting for uncertainty introduced by misidentification and imperfect detection. In the absence of misidentification, our probit formulation also provides a convenient and efficient Gibbs sampler for Bayesian analysis of traditional closed population capture-recapture data.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS783 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Expression profiling of snoRNAs in normal hematopoiesis and AML

Key Points A subset of snoRNAs is expressed in a developmental- and lineage-specific manner during human hematopoiesis. Neither host gene expression nor alternative splicing accounted for the observed differential expression of snoRNAs in a subset of AML.</jats:p

Morphogenesis of the anterior segment in the zebrafish eye

BACKGROUND: The ocular anterior segment is critical for focusing incoming light onto the neural retina and for regulating intraocular pressure. It is comprised of the cornea, lens, iris, ciliary body, and highly specialized tissue at the iridocorneal angle. During development, cells from diverse embryonic lineages interact to form the anterior segment. Abnormal migration, proliferation, differentiation, or survival of these cells contribute to diseases of the anterior segment such as corneal dystrophy, lens cataract, and glaucoma. Zebrafish represent a powerful model organism for investigating the genetics and cell biology of development and disease. To lay the foundation for genetic studies of anterior segment development, we have described the morphogenesis of this structure in zebrafish. RESULTS: As in other vertebrates, the zebrafish anterior segment derives from diverse origins including surface ectoderm, periocular mesenchyme, and neuroepithelium. Similarly, the relative timing of tissue differentiation in the anterior segment is also conserved with other vertebrates. However, several morphogenic features of the zebrafish anterior segment differ with those of higher vertebrates. These include lens delamination as opposed to invagination, lack of iris muscles and ciliary folds, and altered organization in the iridocorneal angle. In addition, substantial dorsal-ventral differences exist within the zebrafish anterior segment. CONCLUSION: Cumulatively, our anatomical findings provide a reference point to utilize zebrafish for genetic studies into the mechanisms of development and maintenance of the anterior segment

The impact of histopathology and NAB2-STAT6 fusion subtype in classification and grading of meningeal solitary fibrous tumor/hemangiopericytoma.

Meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a rare tumor with propensity for recurrence and metastasis. Although multiple classification schemes have been proposed, optimal risk stratification remains unclear, and the prognostic impact of fusion status is uncertain. We compared the 2016 WHO CNS tumor grading scheme (CNS-G), a three-tier system based on histopathologic phenotype and mitotic count, to the 2013 WHO soft-tissue counterpart (ST-G), a two-tier system based on mitotic count alone, in a cohort of 133 patients [59 female, 74 male; mean age 54&nbsp;years (range 20-87)] with meningeal SFT/HPC. Tumors were pathologically confirmed through review of the first tumor resection (n = 97), local recurrence (n = 35), or distant metastasis (n = 1). A STAT6 immunostain showed nuclear expression in 132 cases. NAB2-STAT6 fusion was detected in 99 of 111 successfully tested tumors (89%) including the single STAT6 immunonegative tumor. Tumors were classified by CNS-G as grade 1 (n = 43), 2 (n = 41), or 3 (n = 49), and by ST-G as SFT (n = 84) or malignant SFT (n = 49). Necrosis was present in 16 cases (12%). On follow-up, 42 patients had at least one subsequent recurrence or metastasis (7 metastasis only, 33 recurrence only, 2 patients had both). Twenty-nine patients died. On univariate analysis, necrosis (p = 0.002), CNS-G (p = 0.01), and ST-G (p = 0.004) were associated with recurrence-free (RFS) but not overall survival (OS). NAB2-STAT6 fusion type was not significantly associated with RFS or OS, but was associated with phenotype. A modified ST-G incorporating necrosis showed higher correlation with RFS (p = 0.0006) and remained significant (p = 0.02) when considering only the primary tumors. From our data, mitotic rate and necrosis appear to stratify this family of tumors most accurately and could be incorporated in a future grading scheme

The disarrayed mutation results in cell cycle and neurogenesis defects during retinal development in zebrafish

BACKGROUND: The vertebrate retina is derived from proliferative neuroepithelial cells of the optic cup. During retinal development, cell proliferation and the processes of cell cycle exit and neurogenesis are coordinated in neuroepithelial progenitor cells. Previous studies have demonstrated reciprocal influences between the cell cycle and neurogenesis. However the specific mechanisms and exact relationships of cell cycle regulation and neurogenesis in the vertebrate retina remain largely unknown. RESULTS: We have isolated and characterized a zebrafish mutant, disarrayed (dry(a64)), which exhibits retinal defects in cell cycle regulation and neurogenesis. By 42 hours post fertilization, disarrayed mutants show small eyes and a reduced forebrain. Other aspects of development appear normal. Although retinogenesis is delayed, mutant retinal cells eventually differentiate to all major cell types. Examination of the disarrayed mitotic cycle using BrdU and direct imaging techniques revealed that retinal neuroepithelial cells have an extended cell cycle period and reduced rate of cell cycle exit and neurogenesis, despite the fact that neurogenesis initiates at the appropriate time of development. Genetic mosaic analyses indicate that the cell cycle phenotype of disarrayed is cell-non-autonomous. CONCLUSION: The disarrayed mutant shows defects in both cell cycle regulation and neurogenesis and provides insights into the coordinated regulation of these processes during retinal development

laminin alpha 1 gene is essential for normal lens development in zebrafish

BACKGROUND: Laminins represent major components of basement membranes and play various roles in embryonic and adult tissues. The functional laminin molecule consists of three chains, alpha, beta and gamma, encoded by separate genes. There are twelve different laminin genes identified in mammals to date that are highly homologous in their sequence but different in their tissue distribution. The laminin alpha -1 gene was shown to have the most restricted expression pattern with strong expression in ocular structures, particularly in the developing and mature lens. RESULTS: We identified the zebrafish lama1 gene encoding a 3075-amino acid protein (lama1) that possesses strong identity with the human LAMA1. Zebrafish lama1 transcripts were detected at all stages of embryo development with the highest levels of expression in the developing lens, somites, nervous and urogenital systems. Translation of the lama1 gene was inhibited using two non-overlapping morpholino oligomers that were complementary to sequences surrounding translation initiation. Morphant embryos exhibited an arrest in lens development and abnormalities in the body axis length and curvature. CONCLUSION: These results underline the importance of the laminin alpha 1 for normal ocular development and provide a basis for further analysis of its developmental roles

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure