372 research outputs found

    The Effects of a Test-Taking Skills Intervention on Test Anxiety and Test Performance in 4th Graders

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    Increases in standardized testing have been accompanied by increased reports of test anxiety in younger students. School-based test anxiety interventions can be implemented to decrease test anxiety and improve test performance. Skill-based interventions have effectively addressed both of these variables; however, the research has primarily targeted secondary and university students. The purpose of the current study was to determine if a test-taking skills intervention would decrease test anxiety and improve test performance in 4th grade students. Results indicated that the test-taking skills intervention resulted only in a minor decrease in test anxiety that maintained at 1-month follow-up. Effects on test performance were mixed immediately following the intervention, and test performance was equivalent to baseline levels at the conclusion of the study. Limitations of this study and recommendations for future research are included

    The Psychological Harms of Screening: the Evidence We Have Versus the Evidence We Need

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    BACKGROUND: Systematic reviews for the US Preventive Services Task Force have found less high-quality evidence on psychological than physical harms of screening. To understand the extent of evidence on psychological harms, we developed an evidence map that quantifies the distribution of evidence on psychological harms for five adult screening services. We also note gaps in the literature and make recommendations for future research. METHODS: We systematically searched PubMed, PsycInfo, and CINAHL from 2002 to 2012 for studies of any research design that assessed the burden or frequency of psychological harm associated with screening for: prostate and lung cancers, osteoporosis, abdominal aortic aneurysm (AAA) and carotid artery stenosis (CAS). We also searched for studies that estimated rates of overdiagnosis (a marker for unnecessary labeling). We included studies published in English and used dual independent review to determine study inclusion and to abstract information on design, types of measures, and outcomes assessed. RESULTS: Sixty-eight studies assessing psychological harms met our criteria; 62 % concerned prostate cancer and 16 % concerned lung cancer. Evidence was scant for the other three screening services. Overall, only about one-third of the studies used both longitudinal designs and condition-specific measures (ranging from 0 % for AAA and CAS to 78 % for lung cancer), which can provide the best evidence on harms. An additional 20 studies that met our criteria estimated rates of overdiagnosis in lung or prostate cancer. No studies estimated overdiagnosis for the non-cancer screening services. DISCUSSION: Evidence on psychological harms varied markedly across screening services in number and potential usefulness. We found important evidence gaps for all five screening services. The evidence that we have on psychological harms is inadequate in number of studies and in research design and measures. Future research should focus more clearly on the evidence that we need for decision making about screening

    Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

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    Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

    A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings

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    BACKGROUND: More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. METHODS AND FINDINGS: Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. CONCLUSION: Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia.

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    BACKGROUND: Genetic mutations underlying familial Alzheimer\u27s disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain. METHODS: We engineered a novel App knock-in mouse model (App RESULTS: Leveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The App DISCUSSION: Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology

    Wnt Signalling Pathway Parameters for Mammalian Cells

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    Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model

    Twelve experiments in restorative justice: the Jerry Lee program of randomized trials of restorative justice conferences

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    Objectives: We conducted and measured outcomes from the Jerry Lee Program of 12 randomized trials over two decades in Australia and the United Kingdom (UK), testing an identical method of restorative justice taught by the same trainers to hundreds of police officers and others who delivered it to 2231 offenders and 1179 victims in 1995–2004. The article provides a review of the scientific progress and policy effects of the program, as described in 75 publications and papers arising from it, including previously unpublished results of our ongoing analyses. Methods: After random assignment in four Australian tests diverting criminal or juvenile cases from prosecution to restorative justice conferences (RJCs), and eight UK tests of supplementing criminal or juvenile proceedings with RJCs, we followed intention-to-treat group differences between offenders for up to 18 years, and for victims up to 10 years. Results: We distil and modify prior research reports into 18 updated evidence-based conclusions about the effects of RJCs on both victims and offenders. Initial reductions in repeat offending among offenders assigned to RJCs (compared to controls) were found in 10 of our 12 tests. Nine of the ten successes were for crimes with personal victims who participated in the RJCs, with clear benefits in both short- and long-term measures, including less prevalence of post-traumatic stress symptoms. Moderator effects across and within experiments showed that RJCs work best for the most frequent and serious offenders for repeat offending outcomes, with other clear moderator effects for poly-drug use and offense seriousness. Conclusions: RJ conferences organized and led (most often) by specially-trained police produced substantial short-term, and some long-term, benefits for both crime victims and their offenders, across a range of offense types and stages of the criminal justice processes on two continents, but with important moderator effects. These conclusions are made possible by testing a new kind of justice on a programmatic basis that would allow prospective meta-analysis, rather than doing one experiment at a time. This finding provides evidence that funding agencies could get far more evidence for the same cost from programs of identical, but multiple, RCTs of the identical innovative methods, rather than funding one RCT at a time

    Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

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    Background: Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods: To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results: The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1alpha (HIF-1alpha) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion: In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways
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