3,399 research outputs found

    The role of psychometrics in individual differences research in cognition: A case study of the AX-CPT

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    Investigating individual differences in cognition requires addressing questions not often thought about in standard experimental designs, especially regarding the psychometric properties of the task. Using the AX-CPT cognitive control task as a case study example, we address four concerns that one may encounter when researching the topic of individual differences in cognition. First, we demonstrate the importance of variability in task scores, which in turn directly impacts reliability, particularly when comparing correlations in different populations. Second, we demonstrate the importance of variability and reliability for evaluating potential failures to replicate predicted correlations, even within the same population. Third, we demonstrate how researchers can turn to evaluating psychometric properties as a way of evaluating the feasibility of utilizing the task in new settings (e.g., online administration). Lastly, we show how the examination of psychometric properties can help researchers make informed decisions when designing a study, such as determining the appropriate number of trials for a task

    An Examination of Response Requirements Associated with Teachers\u27 use of Different Opportunities for Student Response During Instruction

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    Providing effective instruction that increases the degree to which students are engaged with the instructional content has been identified as a research-based practice in that it is associated with positive academic and behavioral outcomes. One high-leverage practice for engaging students is the provision of opportunities to respond (OTR) during instruction. However, previous research has shown that teachers at every level typically use OTRs at rates far below research-based recommendations. This study adds to the literature by breaking OTRs into verbal, non-verbal, and partner categories to further examine how teachers typically foster student engagement. Across 1095 total observations, OTR rates were observed to be higher than previous research. However, teachers at every level were found to use simple verbal questioning greater than 75% of the of the time they provided an engagement opportunity. A discussion focuses on what this implies for students with verbal deficits and on practical implications and areas for future research

    Reporting issues in group sequential randomised controlled trials: a systematic review protocol of published journal reports

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    Background: Adaptive designs are somewhat underused, despite prominence given to methodology in the statistical literature. Some concerns relates to robustness of adaptive designs in decision making, acceptability of trial findings to change practice, anxiety about early stopping of trials and worry about wrong decision making. These issues could be linked to inadequate reporting of the conduct of such clinical trials. We assess the reporting of group sequential randomised controlled trials (RCTs), which are one of the most well-understood adaptive designs in the confirmatory setting. Methods: We undertake a systematic review searching Ovid MEDLINE from 1st January 2001 to 23rd September 2014 and including parallel group confirmatory group sequential RCTs that were prospectively designed using the Frequentist approach. Eligible trials are screened for completeness in reporting against the CONSORT 2010 checklist with some proposed modifications to capture issues such as statistical bias correction following early stopping. Descriptive statistics aided with forest plots on CONSORT compliance are presented. Discussion: Reporting of the conduct of adaptive designs is an area which has not been fully explored. Hence, the findings from this study can enlighten us on the adequacy in reporting of well-understood group sequential RCTs as a class of adaptive designs and on ways to address some of the cited concerns. Most importantly, the study can inform policy makers on the adequacy of the current CONSORT statements in enhancing reporting of such adaptive designs

    Radionuclide Contaminant Burdens in Arctic Marine Mammals Harvested During Subsistence Hunting

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    We conducted gamma spectrometric analyses on more than 200 arctic marine mammal tissue samples. These samples were primarily provided by subsistence hunters from northern Alaska, with a smaller number of samples from the Resolute region in Canada. The majority of samples (>90%) had detectable levels of the anthropogenic radionuclide 137Cs, with a mean level observed in all samples of 0.67 Bq/kg dry weight ± 0.81 (SD). Converted to wet weight, the mean was 0.21 Bq/kg ± 0.19 SD. The median activity observed was 0.45 Bq/kg dry weight (0.18 Bq/kg wet weight) with a range from detection limits to 6.7 Bq/kg dry weight (1.1 Bq/kg wet weight). These findings confirm expectations that current anthropogenic gamma emitter burdens in marine mammals used in the North American Arctic as subsistence food resources are well below activities that would normally merit public health concern (~1000 Bq/kg wet weight). Some differences among species and tissues were observed. Beluga tissues had slightly higher mean burdens of 137Cs overall, and epidermis and muscle tissues in bowhead and beluga whales typically had higher burdens than other tissues analyzed. Low levels of the neutron activation product 108mAg (half-life 418 yr.), probably bioaccumulated from bomb fallout sources, were observed in 16 of 17 beluga livers analyzed, but were not found in any other tissues of beluga or in any other species sampled. A subset of 39 samples of various tissues was analyzed for the alpha and beta emitters 239,240Pu and 90Sr. Plutonium levels were near the threshold of detectability (~0.1 Bq/kg dry weight) in 6 of the 39 samples; all other samples had no detectable plutonium. A detectable level of 90Sr (10.3 ± 1.0 Bq/kg dry weight) was observed in only one of the 39 samples analyzed, a bowhead epidermis sample. Although the accumulation of 108mAg has not been previously reported in any marine mammal livers, all of our analytical measurements indicate that only very low levels of anthropogenic radioactivity are associated with marine mammals harvested and consumed in the North American Arctic.On a effectuĂ© des analyses gamma-spectromĂ©triques sur plus de 200 Ă©chantillons de tissus prĂ©levĂ©s sur des mammifĂšres marins. La plupart de ces Ă©chantillons Ă©taient fournis par des chasseurs de subsistance de l'Alaska septentrional, et un petit nombre venaient de la rĂ©gion de Resolute au Canada. La majoritĂ© des Ă©chantillons (> 90 p. cent) contenaient des niveaux dĂ©tectables du radionuclĂ©ide anthropique 137Cs, avec un niveau moyen observĂ© dans tous les Ă©chantillons de 0,67 Bq/kg de poids sec ± 0,81 (Ă©cart-type). Convertie en poids frais, la moyenne Ă©tait de 0,21 Bq/kg ± 0,19 d'Ă©cart-type. L'activitĂ© mĂ©diane observĂ©e Ă©tait de 0,45 Bq/kg de poids sec (0,18 Bq/kg de poids frais) avec une fourchette allant des seuils de dĂ©tection jusqu'Ă  6,7 Bq/kg de poids sec (1,1 Bq/kg de poids frais). Ces rĂ©sultats confirment les rĂ©ponses prĂ©vues, Ă  savoir que les charges actuelles des Ă©metteurs gamma anthropiques prĂ©sentes chez les mammifĂšres marins utilisĂ©s en AmĂ©rique du Nord comme ressource de subsistance sont bien infĂ©rieures aux niveaux qui voudraient normalement qu'on s'inquiĂšte pour la santĂ© publique (~1000 Bq/kg de poids frais). On a observĂ© certaines diffĂ©rences dans les espĂšces et les tissus. Dans l'ensemble, les tissus prĂ©levĂ©s sur le bĂ©louga contenaient des charges moyennes de 137Cs lĂ©gĂšrement plus Ă©levĂ©es, et l'Ă©piderme et les tissus musculaires de la baleine borĂ©ale et du bĂ©louga avaient gĂ©nĂ©ralement des charges supĂ©rieures Ă  celles trouvĂ©es dans les autres tissus analysĂ©s. Dans 16 des 17 foies de bĂ©louga analysĂ©s, on a observĂ© de faibles niveaux du produit d'activation neutronique 108mAg (demi-vie 418 annĂ©es), dont la bioaccumulation est probablement due Ă  des retombĂ©es de bombes atomiques, mais on n'en a observĂ© aucune trace dans les autres tissus du bĂ©louga ou de toute autre espĂšce Ă©chantillonnĂ©e. On a analysĂ© un sous-ensemble de 39 Ă©chantillons provenant de tissus divers pour savoir s'ils contenaient des Ă©metteurs alpha et bĂȘta 239,240Pu et 90Sr. Dans 6 des 39 Ă©chantillons, les niveaux de plutonium Ă©taient proches du seuil de dĂ©tectabilitĂ© (~ 0,1 Bq/kg de poids sec), et on n'a pas trouvĂ© de plutonium dĂ©tectable dans aucun des autres Ă©chantillons. On a observĂ© un niveau dĂ©tectable de 90Sr (10,3 ± 1,0 Bq/kg de poids sec) dans un seul des 39 Ă©chantillons analysĂ©s, soit un Ă©chantillon d'Ă©piderme de baleine borĂ©ale. Bien qu'on n'ait jamais rapportĂ© auparavant une accumulation de 108mAg dans le foie d'un mammifĂšre marin, toutes nos mesures analytiques rĂ©vĂšlent que les mammifĂšres marins faisant l'objet d'une activitĂ© d'exploitation et consommĂ©s dans l'Arctique nord-amĂ©ricain ne prĂ©sentent que de trĂšs faibles niveaux de radioactivitĂ© anthropique

    Food and earth systems: Priorities for climate change adaptation and mitigation for agriculture and food systems

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    Human activities and their relation with land, through agriculture and forestry, are significantly impacting Earth system functioning. Specifically, agriculture has increasingly become a key sector for adaptation and mitigation initiatives that address climate change and help ensure food security for a growing global population. Climate change and agricultural outcomes influence our ability to reach targets for at least seven of the 17 Sustainable Development Goals. By 2015, 103 nations had committed themselves to reduce greenhouse gas emissions from agriculture, while 102 countries had prioritized agriculture in their adaptation agenda. Adaptation and mitigation actions within agriculture still receive insufficient support across scales, from local to international level. This paper reviews a series of climate change adaptation and mitigation options that can support increased production, production efficiency and greater food security for 9 billion people by 2050. Climate-smart agriculture can help foster synergies between productivity, adaptation, and mitigation, although trade-offs may be equally apparent. This study highlights the importance of identifying and exploiting those synergies in the context of Nationally Determined Contributions. Finally, the paper points out that keeping global warming to 2 °C above pre-industrial levels by 2100 requires going beyond the agriculture sector and exploring possibilities with respect to reduced emissions from deforestation, food loss, and waste, as well as from rethinking human diets

    T1DBase: update 2011, organization and presentation of large-scale data sets for type 1 diabetes research

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    T1DBase (http://www.t1dbase.org) is web platform, which supports the type 1 diabetes (T1D) community. It integrates genetic, genomic and expression data relevant to T1D research across mouse, rat and human and presents this to the user as a set of web pages and tools. This update describes the incorporation of new data sets, tools and curation efforts as well as a new website design to simplify site use. New data sets include curated summary data from four genome-wide association studies relevant to T1D, HaemAtlas—a data set and tool to query gene expression levels in haematopoietic cells and a manually curated table of human T1D susceptibility loci, incorporating genetic overlap with other related diseases. These developments will continue to support T1D research and allow easy access to large and complex T1D relevant data sets

    How U.S. Ocean Policy and Market Power Can Reform the Coral Reef Wildlife Trade

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    As the world’s largest importer of marine ornamental species for the aquaria, curio, home dĂ©cor, and jewelry industries, the United States has an opportunity to leverage its considerable market power to promote more sustainable trade and reduce the effects of ornamental trade stress on coral reefs worldwide. Evidence indicates that collection of some coral reef animals for these trades has caused virtual elimination of local populations, major changes in age structure, and promotion of collection practices that destroy reef habitats. Management and enforcement of collection activities in major source countries such as Indonesia and the Philippines remain weak. Strengthening US trade laws and enforcement capabilities combined with increasing consumer and industry demand for responsible conservation can create strong incentives for improving management in source countries. This is particularly important in light of the March 2010 failure of the parties to the Convention on International Trade in Endangered Species (CITES) to take action on key groups of corals

    Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion.

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    Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance

    Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression

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    Despite advances in the clinical management of childhood acute myeloid leukemia (AML) during the last decades, outcome remains fatal in approximately one third of patients. Primary chemoresistance, relapse and acute and long-term toxicities to conventional myelosuppressive therapies still constitute significant challenges and emphasize the unmet need for effective targeted therapies. Years of scientific efforts have translated into extensive insights on the heterogeneous spectrum of genetics and oncogenic signaling pathways of AML and identified a subset of patients characterized by upregulation of HOXA and HOXB homeobox genes and myeloid ecotropic virus insertion site 1 (MEIS1). Aberrant HOXA/MEIS1 expression is associated with genotypes such as rearrangements in Histone-lysine N-methyltransferase 2A (KMT2A-r), nucleoporin 98 (NUP98-r) and mutated nucleophosmin (NPM1c) that are found in approximately one third of children with AML. AML with upregulated HOXA/MEIS1 shares a number of molecular vulnerabilities amenable to recently developed molecules targeting the assembly of protein complexes or transcriptional regulators. The interaction between the nuclear scaffold protein menin and KMT2A has gained particular interest and constitutes a molecular dependency for maintenance of the HOXA/MEIS1 transcription program. Menin inhibitors disrupt the menin-KMT2A complex in preclinical models of KMT2A-r, NUP98-r and NPM1c acute leukemias and its occupancy at target genes leading to leukemic cell differentiation and apoptosis. Early-phase clinical trials are either ongoing or in development and preliminary data suggests tolerable toxicities and encouraging efficacy of menin inhibitors in adults with relapsed or refractory KMT2A-r and NPM1c AML. The Pediatric Acute Leukemia/European Pediatric Acute Leukemia (PedAL/EUPAL) project is focused to advance and coordinate informative clinical trials with new agents and constitute an ideal framework for testing of menin inhibitors in pediatric study populations. Menin inhibitors in combination with standard chemotherapy or other targeting agents may enhance anti-leukemic effects and constitute rational treatment strategies for select genotypes of childhood AML, and provide enhanced safety to avoid differentiation syndrome. In this review, we discuss the pathophysiological mechanisms in KMT2A-r, NUP98-r and NPM1c AML, emerging molecules targeting the HOXA/MEIS1 transcription program with menin inhibitors as the most prominent examples and future therapeutic implications of these agents in childhood AML.</p
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