Training and Generalization of Complex Auditory-Visual Conditional Discriminations in Individuals With Autism: New Procedures Using Dynamic Stimuli

Individuals with autism and other developmental disabilities often have difficulty learning auditory-visual conditional discriminations that are important for early communication and generalization may be restricted. Programs for teaching these individuals often involve the fading (gradual change) of stimuli in small steps across trials. Failure to establish desired discriminations occurs when the fading does not direct attention to the relevant critical aspects of the stimuli. The research described here illustrates new attention-shaping procedures for teaching complex auditory-visual discriminations and assessing generalization. The major purpose was to begin evaluation of the dual-modality transfer procedures with abstract stimulus sets that would rule out pre-experimental learning as an explanation of cross-modal (i.e., visual-to-auditory) transfer of stimulus control. In one procedure, auditory samples (pairs of same and different tones) were added to visual stimuli (pairs of same and different forms that participants matched already) presented as samples and comparisons. Across-trial contrast fading then gradually ‘vanished’ the visual samples, in order to establish conditional control of comparison selections by the pairs of same and different tones. Generalization then was assessed using new frequencies of the tones. Another procedure introduced a novel dynamic fading method. The visual cues that already controlled responding were erased actively within trials (like apparent movement) and cumulatively across trials. After fading, conditional control was demonstrated by the auditory samples only. Generalization was tested using tones with frequencies different from the training stimuli. Presented at the 38th Annual Convention of the Association for Behavior Analysis International

ESTABLISHMENT AND REORGANIZATION OF DERIVED ARBITRARY RELATIONS FOLLOWING IDENTITY MATCHING-TO-SAMPLE TRAINING WITH SPECIFIC CONSEQUENCES

No Experimento 1, seis participantes foram treinados em um procedimento MTS de identidade (IDMTS) para estabelecer relações estímulo-estímulo A1A1, A2A2, A3A3; B1B1, B2B2, B3B3; e C1C1, C2C2, C3C3. Respostas corretas resultavam na apresentação de consequências específicas, Sr1, Sr2 e Sr3. Uma resposta de consumação às consequências específicas foi requerida para que os participantes pudessem coletar os pontos nas tentativas de treino. O procedimento MTS arbitrário foi utilizado para documentar a formação de três classes de equivalência A1B1C1Sr1, A2B2C2Sr2 e A3B3C3Sr3. Em uma fase subsequente, o IDMTS com consequências específicas foi empregado para treinar as relações D1D1, D2D2 e D3D3. Os estímulos D eram fotografias de faces humanas expressando alegria (D1), tristeza (D2) e neutralidade (D3). Por último, avaliações por meio do diferencial semântico atestaram a ocorrência da transferência das funções (i.e., “significados”) dos estímulos D para os estímulos C e para Sr1 e Sr3. Estes resultados sugeriram que as classes ABCSr se expandiram para incluir os estímulos significativos D (i.e., A1B1C1D1Sr1, A2B2C2D2Sr2 e A3B3C3D3Sr3). No Experimento 2 verificou-se que, para cinco participantes, o procedimento de reversão das consequências específicas Sr1 e Sr2 em relação aos estímulos C1, C2 e D1 e D2 deu origem a duas classes de equivalência reorganizadas (A1B1C2D2Sr2 e A2B2C1D1Sr1). Paralelamente, os dados do diferencial semântico documentaram a reversão dos significados atribuídos previamente aos estímulos D1 e D2. Estes achados sugerem que o procedimento de reversão reorganizou as classes de estímulos bem como seus significados. Porém, resultados análogos não foram reportados para as consequências específicas.Palavras-chave: Matching-to-sample de identidade, consequências específicas, classes de equivalência, reorganização de classes de equivalência, transferência de função, universitáriosIn Experiment 1, six participants were given identity matching to sample (IDMTS) training that established the stimulus- stimulus relations A1A1, A2A2, A3A3; B1B1, B2B2, B3B3; and C1C1, C2C2, C3C3. Correct responses resulted in presentations of class-specific consequences, Sr1, Sr2, and Sr3. Consummatory responses to the class-specific consequences were required to collect points on training trials. Subsequent tests used arbitrary matching to sample to confirm the formation of three equivalence classes, A1B1C1Sr1, A2B2C2Sr2, and A3B3C3Sr3. Next, IDMTS, with the specific consequences, was used to train D1D1, D2D2 and D3D3 relations. These D stimuli were pictures of human faces portraying happiness (D1), sadness (D2), and neutrality (D3). Finally, tests used semantic differential ratings to document transfer of functions (i.e., “meanings”) of the D stimuli to the C stimuli and to the Sr1 and Sr3 stimuli, in accord with class membership. These results suggest expansion of the ABCSr classes to include the meaningful D stimuli (i.e., A1B1C1D1Sr1, A2B2C2D2Sr2, and A3B3C3D3Sr3). Experiment 2 verified that, for five participants, reversals of the class-specific consequences Sr1 and Sr2 with respect to stimuli C1, and C2, and D1 and D2, gave rise to the two reorganized equivalence classes A1B1C2D2Sr2 and A2B2C1D1Sr1. Semantic differential ratings then documented reversals of the meanings given to stimuli C1 and C2. Also, semantic differential ratings documented the reversals of the meanings of C stimuli in accordance with their reorganized class-memberships with D stimuli. However, analogous reversals of function transfer were not observed for the class-specific consequences. Key words: Identity matching-to-sample, class-specific consequences, equivalence classes, reorganization of equivalence classes, transfer of functions, undergraduates

Exploring short gamma-ray bursts as gravitational-wave standard sirens

Recent observations support the hypothesis that a large fraction of "short-hard" gamma-ray bursts (SHBs) are associated with compact binary inspiral. Since gravitational-wave (GW) measurements of well-localized inspiraling binaries can measure absolute source distances, simultaneous observation of a binary's GWs and SHB would allow us to independently determine both its luminosity distance and redshift. Such a "standard siren" (the GW analog of a standard candle) would provide an excellent probe of the relatively nearby universe's expansion, complementing other standard candles. In this paper, we examine binary measurement using a Markov Chain Monte Carlo technique to build the probability distributions describing measured parameters. We assume that each SHB observation gives both sky position and the time of coalescence, and we take both binary neutron stars and black hole-neutron star coalescences as plausible SHB progenitors. We examine how well parameters particularly distance) can be measured from GW observations of SHBs by a range of ground-based detector networks. We find that earlier estimates overstate how well distances can be measured, even at fairly large signal-to-noise ratio. The fundamental limitation to determining distance proves to be a degeneracy between distance and source inclination. Overcoming this limitation requires that we either break this degeneracy, or measure enough sources to broadly sample the inclination distribution. (Abridged)Comment: 19 pages, 10 figures. Accepted for publication in ApJ; this version incorporates referee's comments and criticism

A genomic atlas of systemic interindividual epigenetic variation in humans.

BACKGROUND: DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific. RESULTS: For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues. CONCLUSIONS: In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease

Tigers Need Cover: Multi-Scale Occupancy Study of the Big Cat in Sumatran Forest and Plantation Landscapes

The critically endangered Sumatran tiger (Panthera tigris sumatrae Pocock, 1929) is generally known as a forest-dependent animal. With large-scale conversion of forests into plantations, however, it is crucial for restoration efforts to understand to what extent tigers use modified habitats. We investigated tiger-habitat relationships at 2 spatial scales: occupancy across the landscape and habitat use within the home range. Across major landcover types in central Sumatra, we conducted systematic detection, non-detection sign surveys in 47, 17×17 km grid cells. Within each cell, we surveyed 40, 1-km transects and recorded tiger detections and habitat variables in 100 m segments totaling 1,857 km surveyed. We found that tigers strongly preferred forest and used plantations of acacia and oilpalm, far less than their availability. Tiger probability of occupancy covaried positively and strongly with altitude, positively with forest area, and negatively with distance-to-forest centroids. At the fine scale, probability of habitat use by tigers across landcover types covaried positively and strongly with understory cover and altitude, and negatively and strongly with human settlement. Within forest areas, tigers strongly preferred sites that are farther from water bodies, higher in altitude, farther from edge, and closer to centroid of large forest block; and strongly preferred sites with thicker understory cover, lower level of disturbance, higher altitude, and steeper slope. These results indicate that to thrive, tigers depend on the existence of large contiguous forest blocks, and that with adjustments in plantation management, tigers could use mosaics of plantations (as additional roaming zones), riparian forests (as corridors) and smaller forest patches (as stepping stones), potentially maintaining a metapopulation structure in fragmented landscapes. This study highlights the importance of a multi-spatial scale analysis and provides crucial information relevant to restoring tigers and other wildlife in forest and plantation landscapes through improvement in habitat extent, quality, and connectivity

Patterns of Hybrid Loss of Imprinting Reveal Tissue- and Cluster-Specific Regulation

Background: Crosses between natural populations of two species of deer mice, Peromyscus maniculatus (BW), and P. polionotus (PO), produce parent-of-origin effects on growth and development. BW females mated to PO males (bw6po) produce growth-retarded but otherwise healthy offspring. In contrast, PO females mated to BW males (PO6BW) produce overgrown and severely defective offspring. The hybrid phenotypes are pronounced in the placenta and include PO6BW conceptuses which lack embryonic structures. Evidence to date links variation in control of genomic imprinting with the hybrid defects, particularly in the PO6BW offspring. Establishment of genomic imprinting is typically mediated by gametic DNA methylation at sites known as gDMRs. However, imprinted gene clusters vary in their regulation by gDMR sequences. Methodology/Principal Findings: Here we further assess imprinted gene expression and DNA methylation at different cluster types in order to discern patterns. These data reveal PO6BW misexpression at the Kcnq1ot1 and Peg3 clusters, both of which lose ICR methylation in placental tissues. In contrast, some embryonic transcripts (Peg10, Kcnq1ot1) reactivated the silenced allele with little or no loss of DNA methylation. Hybrid brains also display different patterns of imprinting perturbations. Several cluster pairs thought to use analogous regulatory mechanisms are differentially affected in the hybrids. Conclusions/Significance: These data reinforce the hypothesis that placental and somatic gene regulation differs significantly, as does that between imprinted gene clusters and between species. That such epigenetic regulatory variatio

Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency

The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro–B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP–keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell–activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)