57 research outputs found

    Unitization during Category Learning

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    Five experiments explored the question of whether new perceptual units can be developed if they are diagnostic for a category learning task, and if so, what are the constraints on this unitization process? During category learning, participants were required to attend either a single component or a conjunction of five components in order to correctly categorize an object. In Experiments 1-4, some evidence for unitization was found in that the conjunctive task becomes much easier with practice, and this improvement was not found for the single component task, or for conjunctive tasks where the components cannot be unitized. Influences of component order (Experiment 1), component contiguity (Experiment 2), component proximity (Experiment 3), and number of components (Experiment 4) on practice effects were found. Using a Fourier Transformation method for deconvolving response times (Experiment 5), prolonged practice effects yielded responses that were faster than expected by analytic model that integrate evidence from independently perceived components

    Searching for Higgs : From LEP towards LHC

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    After a brief introduction to the theoretical basis of the Higgs mechanism for generating the masses of elementary particles, the experimental searches for Higgs particles will be summarized, from bounds at LEP to inferences for LHC. The report will focus on the Standard Model, though some central results on extended Higgs systems, as conjectured for example in supersymmetric theories, will also be recapitulated. Alternative scenarios based on spontaneous symmetry breaking by novel strong interactions are adumbrated at the theoretical level.Comment: Added reference

    Bisphenol A and its analogues: A comprehensive review to identify and prioritize effect biomarkers for human biomonitoring

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    Human biomonitoring (HBM) studies have demonstrated widespread and daily exposure to bisphenol A (BPA). Moreover, BPA structural analogues (e.g. BPS, BPF, BPAF), used as BPA replacements, are being increasingly detected in human biological matrices. BPA and some of its analogues are classified as endocrine disruptors suspected of contributing to adverse health outcomes such as altered reproduction and neurodevelopment, obesity, and metabolic disorders among other developmental and chronic impairments. One of the aims of the H2020 European Human Biomonitoring Initiative (HBM4EU) is the implementation of effect biomarkers at large scales in future HBM studies in a systematic and standardized way, in order to complement exposure data with mechanistically-based biomarkers of early adverse effects. This review aimed to identify and prioritize existing biomarkers of effect for BPA, as well as to provide relevant mechanistic and adverse outcome pathway (AOP) information in order to cover knowledge gaps and better interpret effect biomarker data. A comprehensive literature search was performed in PubMed to identify all the epidemiologic studies published in the last 10 years addressing the potential relationship between bisphenols exposure and alterations in biological parameters. A total of 5716 references were screened, out of which, 119 full-text articles were analyzed and tabulated in detail. This work provides first an overview of all epigenetics, gene transcription, oxidative stress, reproductive, glucocorticoid and thyroid hormones, metabolic and allergy/immune biomarkers previously studied. Then, promising effect biomarkers related to altered neurodevelopmental and reproductive outcomes including brainderived neurotrophic factor (BDNF), kisspeptin (KiSS), and gene expression of nuclear receptors are prioritized, providing mechanistic insights based on in vitro, animal studies and AOP information. Finally, the potential of omics technologies for biomarker discovery and its implications for risk assessment are discussed. To the best of our knowledge, this is the first effort to comprehensively identify bisphenol-related biomarkers of effect for HBM purposes.European Union Commission H2020-EJP-HBM4EU 733032HBM4EU Initiativ

    Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

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    Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

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    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    Similarity, interactive activation, and mapping.

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    The question of What makes things seem similar? is important both because of similarity's pivotal role in theories of cognition and because of an intrinsic interest in how people make comparisons. This dissertation argues that psychological assessments of similarity involve more than listing the features of the things to be compared and comparing the lists for overlap. Instead, when comparing things that are hierarchically or propositionally structured, the parts of one thing must be aligned or placed in correspondence with the other thing's parts. In eleven experiments on human subjects this need for structural alignment is exhibited in similarity ratings, same/different responses, ease of comparison judgments, and feature match identifications. Three quantitative models of similarity are developed and applied to the empirically obtained data. The model with the best overall fit assumes an interactive activation process whereby correspondences between the parts of compared things mutually and concurrently influence each other. An essential aspect of this interactive activation model is that matching features increase similarity more if they belong to parts that are placed in correspondence. In turn, parts are placed in correspondence if they have many matching features in common, and if they are consistent with other developing correspondences. Predictions made by this model are empirically confirmed and the model is applied to results in problem solving, similarity comparisons, perception, and analogical reasoning.Ph.D.Experimental psychologyPsychologyQuantitative psychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/128748/2/9135601.pd

    Who killed in Rwanda’s genocide? Micro-space, social influence and individual participation in intergroup violence

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    In episodes of intergroup violence, which group members participate and which do not? Although such violence is frequently framed as occurring between distinct ethnic, racial or sectarian groups, it is easily overlooked that it is usually only a subset of the group’s members who in fact participate in the violence. In predicting participation, extant research has privileged an atomistic approach and identified individual attributes indicative of a predisposition to violence. I suggest instead that a situational approach should complement the atomistic paradigm and present evidence that an individual’s micro-spatial environment is an important predictor of differential participation in intergroup violence. Using GIS data on 3,426 residents from one community, I map the household locations of participants, non-participants, and victims of Rwanda’s 1994 genocide. I find that participants are likely to live either in the same neighbourhood or in the same household as other participants. Specifically, as the number of violent to nonviolent individuals in an individual’s neighbourhood or household increases, the likelihood of this individual’s participation also increases. In explaining these neighbourhood and household effects, I suggest social influence is the mechanism at work. As micro-spatial distance decreases, micro-social interaction increases. Neighbours and household members exert influence for and against participation. Participation then may be as much the product of social interaction as of individual agency. What neighbours and family members think, say and do may influence participation in collective action such as intergroup violence. The conceptualization of neighbourhoods and households as micro-spheres of influences suggests the importance of social structure as a determinant of participation

    Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen

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    Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 × 109/L vs > 30 × 109/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome
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