Activation of Operational Thinking During Arithmetic Practice Hinders Learning And Transfer

Many children in the U.S. initially come to understand the equal sign operationally, as a symbol meaning “add up the numbers” rather than relationally, as an indication that the two sides of an equation share a common value. According to a change-resistance account (McNeil & Alibali, 2005), children\u27s operational ways of thinking are never erased, and when activated, can interfere with mathematics learning and performance, even in educated adults. To test this theory, undergraduates practiced unfamiliar multiplication facts (e.g., 17-times table) in one of three conditions that differed in terms of how the equal sign was represented in the problems. In the operational words condition, the equal sign was replaced by operational words (e.g., multiplies to ). In the relational words condition, the equal sign was replaced by relational words (e.g., is equivalent to ). In the control condition, the equal sign was used in all problems. The hypothesis was that undergraduates\u27 fluency with practiced facts and transfer problems would be hindered in the operational words condition compared to the other conditions. Results supported this hypothesis, indicating that the activation of operational thinking is indeed detrimental to learning and transfer, even in educated adults

Molecular and cytological features of the mouse B-cell lymphoma line iMyc(Eμ)-1

BACKGROUND: Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMyc(Eμ )mice may provide a model system for the study of the mechanism by which human MYC facilitates the initiation and progression of B cell and plasma cell neoplasms in human beings. We have recently shown that gene-targeted iMyc(Eμ )mice that carry a His(6)-tagged mouse Myc cDNA, Myc(His), just 5' of the immunoglobulin heavy-chain enhancer, Eμ, are prone to B cell and plasma cell tumors. The predominant tumor (~50%) that arose in the iMyc(Eμ )mice on the mixed genetic background of segregating C57BL/6 and 129/SvJ alleles was LBL. The purpose of this study was to establish and characterize a cell line, designated iMyc(Eμ)-1, for the in-depth evaluation of LBL in vitro. METHODS: The morphological features and the surface marker expression profile of the iMyc(Eμ)-1 cells were evaluated using cytological methods and FACS, respectively. The cytogenetic make-up of the iMyc(Eμ)-1 cells was assessed by spectral karyotyping (SKY). The expression of the inserted Myc(His )gene was determined using RT-PCR and qPCR. Clonotypic immunoglobulin gene arrangements were detected by Southern blotting. The global gene expression program of the iMyc(Eμ)-1 cells and the expression of 768 "pathway" genes were determined with the help of the Mouse Lymphochip(© )and Superarray(© )cDNA micro- and macroarrays, respectively. Array results were verified, in part, by RT-PCR and qPCR. RESULTS: Consistent with their derivation from LBL, the iMyc(Eμ)-1 cells were found to be neoplastic IgM(high)IgD(low )lymphoblasts that expressed typical B-cell surface markers including CD40, CD54 (ICAM-1), CD80 (B7-1) and CD86 (B7-2). The iMyc(Eμ)-1 cells harbored a reciprocal T(9;11) and three non-reciprocal chromosomal translocations, over-expressed Myc(His )at the expense of normal Myc, and exhibited gene expression changes on Mouse Lymphochip(© )microarrays that were consistent with Myc(His)-driven B-cell neoplasia. Upon comparison to normal B cells using eight different Superarray(© )cDNA macroarrays, the iMyc(Eμ)-1 cells showed the highest number of changes on the NFκB array. CONCLUSION: The iMyc(Eμ)-1 cells may provide a uniquely useful model system to study the growth and survival requirements of Myc-driven mouse LBL in vitro

Challenges in mathematical cognition: a collaboratively-derived research agenda

This paper reports on a collaborative exercise designed to generate a coherent agenda for research on mathematical cognition. Following an established method, the exercise brought together 16 mathematical cognition researchers from across the fields of mathematics education, psychology and neuroscience. These participants engaged in a process in which they generated an initial list of research questions with the potential to significantly advance understanding of mathematical cognition, winnowed this list to a smaller set of priority questions, and refined the eventual questions to meet criteria related to clarity, specificity and practicability. The resulting list comprises 26 questions divided into six broad topic areas: elucidating the nature of mathematical thinking, mapping predictors and processes of competence development, charting developmental trajectories and their interactions, fostering conceptual understanding and procedural skill, designing effective interventions, and developing valid and reliable measures. In presenting these questions in this paper, we intend to support greater coherence in both investigation and reporting, to build a stronger base of information for consideration by policymakers, and to encourage researchers to take a consilient approach to addressing important challenges in mathematical cognition

Incidence of erythropoietin antibody-mediated pure red cell aplasia: the Prospective Immunogenicity Surveillance Registry (PRIMS)

Background: Subcutaneous administration of Eprex(®) (epoetin alfa) in patients with chronic kidney disease (CKD) was contraindicated in the European Union between 2002 and 2006 after increased reports of anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA). The Prospective Immunogenicity Surveillance Registry (PRIMS) was conducted to estimate the incidence of antibody-mediated PRCA with subcutaneous administration of a new coated-stopper syringe presentation of Eprex(®) and to compare this with the PRCA incidence with subcutaneous NeoRecormon(®) (epoetin beta) and Aranesp(®) (darbepoetin alfa). Methods: PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex(®), NeoRecormon(®) or Aranesp(®) for anaemia were enrolled and followed for up to 3 years. Unexplained loss or lack of effect (LOE), including suspected PRCA, was reported, with antibody testing for confirmation of PRCA. Results: Of the 15 333 patients enrolled, 5948 received Eprex(®) (8377 patient-years) and 9356 received NeoRecormon(®)/Aranesp(®) (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex(®), n = 3; NeoRecormon(®), n = 1; Aranesp(®), n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4-104.7) for Eprex(®) versus 14.0/100 000 patient-years (95% CI 1.7-50.6) for NeoRecormon(®)/Aranesp(®). The incidence of PRCA with Eprex(®) was not significantly different versus comparator ESAs (rate ratio: 2.56; 95% CI 0.43-15.31). An analysis based on observed time produced similar findings. Conclusion: This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex(®), or NeoRecormon(®) or Aranesp(®).This study was funded by Janssen, Pharmaceutical Companies of Johnson & Johnson

Regulating working families in the European Union: a history of disjointed strategies

Families in market economies worldwide have long been confronted with the demands of participating in paid work and providing care for their dependent members. The social, economic and political contexts within which families do so differ from country to country but an increasing number of governments are being asked to engage, or better engage, with this important area of public policy. What seems like a relatively simple goal – to enable families to better balance care-giving and paid employment – has raised several difficulties and dilemmas for policy makers which have been approached in different ways. This paper aims to identify and critique the nature and development of the means by which legal engagement with work-family reconciliation has, historically, been framed in the European Union. In doing so, and with reference to specific cohorts of workers, we demonstrate how disjointed the strategies are in relation to working carers and argue that the EU is unlikely to provide the legal framework necessary to bring about effective change in this fundamentally important area of social policy

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Challenges in Mathematical Cognition: A Collaboratively-Derived Research Agenda

This paper reports on a collaborative exercise designed to generate a coherent agenda for research on mathematical cognition. Following an established method, the exercise brought together 16 mathematical cognition researchers from across the fields of mathematics education,psychology and neuroscience. These participants engaged in a process in which they generated an initial list of research questions with the potential to significantly advance understanding of mathematical cognition, winnowed this list to a smaller set of priority questions, and refined the eventual questions to meet criteria related to clarity, specificity and practicability. The resulting list comprises 26 questions divided into sixbroad topic areas: elucidating the nature of mathematical thinking, mapping predictors and processes of competence development, charting developmental trajectories and their interactions, fostering conceptual understanding and procedural skill, designing effective interventions, and developing valid and reliable measures. In presenting these questions in this paper, we intend to support greater coherence in both investigation and reporting, to build a stronger base of information for consideration by policymakers, and to encourage researchers to take a consilient approach to addressing important challenges in mathematical cognition.</p

The Global Health System: Actors, Norms, and Expectations in Transition

In the first in a series of four articles highlighting the changing nature of global health institutions, Nicole Szlezák and colleagues outline the origin and aim of the series

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure