402 research outputs found

    The Importance of Being Earnest

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    Memory Functioning for Personally Experienced and Witnessed Events in Children with Autism and the Implications for Educators, Mental Health Professionals, and the Law

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    Several researchers have hypothesized a deficit in memory processing to exist in children with a diagnosis of autism spectrum disorder (ASD). This hypothesis has been supported by findings of deficient recall and recognition ability in children with ASD. Specifically, research has pointed to greater deficits in their ability to recall events related to the self as opposed to others. However, such research has not explored how memory functioning would be impacted when an event with an emotional tenor was used and when a forced choice yes/no paradigm was used to extricate what was remembered from the event. The current study aimed to compare recognition memory for personally experienced and witnessed events using a mock stranger-danger scenario. Forty-two children with ASD underwent either a personally experienced or witnessed event. Following the event, the child was administered a survey assessing their recognition of both thematic and detailed content from the event. No statistically significant differences were identified for recognition memory between the personally experienced and witnessed events. While differences between the groups were not found to be significant, it was revealed that there was a trend towards significance for better recognition of details for the witnessed than for the personally experienced event. Implications for future research are discussed as well as the potential impact of such findings in the terms of forensic and educational domains

    Exploring the landscape of relationships and sexuality education in primary schools in New Zealand

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    From Introduction: Learning about sex, relationships, and sexuality in education contexts is a perennially controversial issue, no matter where in the world. Is it the role of the parents? Is it the role of the school? At what age or stage should this learning occur? How much information is “too much information”, or “too little information”? A search for new stories1 from recent years in New Zealand reveals such headlines as “More sex education should be taught earlier”. “Some schools wary of sex education for young”. “Principals reject sex education 'pleasure zone' teaching”. “Leave sex education to parents? No thanks”. “Sex ed's an issue for families, not schools”. These sometimes conflicting headlines provide some insight into the controversy surrounding sex, relationships, and sexuality education in schools as it plays out in the wider public arena. This research aims to shed light on the current landscape of relationships and sexuality education in primary schools in New Zealand, in order contribute to the limited research base that exists in this area

    Using participatory methods to design an mHealth intervention for a low income country, a case study in Chikwawa, Malawi

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    This research was conducted by the Scotland Chikwawa Health Initiative. We would like to thank Sothin Ziba and Rossanie Daudi for their contribution to the facilitation of the focus group discussions. This study was funded by the Scottish Government grant MW22.Peer reviewedPublisher PD

    GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment

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    The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis

    Seizure burden in severe earlyâ life epilepsy: Perspectives from parents

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    ObjectivesSeizure burden is typically measured by seizure frequency yet it entails more than seizure counts, especially for people with severe epilepsies and their caregivers. We aimed to characterize the multiâ faceted nature of seizure burden in young people and their parents who are living with severe earlyâ life epilepsies.MethodsA oneâ day workshop and a series of teleconferences were held with parents of children with severe, refractory epilepsy of earlyâ life origin and providers for children with epilepsy. The workshop sessions were structured as focus groups and aimed to identify components of seizure burden and their impact from the perspective of parents and providers. Data were gathered, organized, and refined during the workshop using an iterative 4â step process that drew upon grounded theory.ResultsThree primary components of seizure burden were identified: frequency, severity, and unpredictability, which was as important if not more important at times than frequency and severity. Caregivers noted that the impacts of seizures were experienced as acuteâ immediate consequences, longerâ term consequences, and as chronic effects that develop and evolve over time. The severity of the child’s neurological and medical status as well as where in the disease journey a family was represented additional contextual factors that influenced the experience of seizure burden.SignificancePatientâ reported and patientâ centered outcomes are increasingly incorporated into the evaluation of treatment effectiveness. Without understanding how the disease creates burden for the patient (or family), it is difficult to know how to assess the impact of treatment. Our preliminary findings indicate seizure burden is a complex construct and unpredictability can be as important as frequency and severity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149509/1/epi412319_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149509/2/epi412319.pd

    Massive amplitudes on the Coulomb branch of N=4 SYM

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    We initiate a systematic study of amplitudes with massive external particles on the Coulomb-branch of N=4 super Yang Mills theory: 1) We propose that (multi-)soft-scalar limits of massless amplitudes at the origin of moduli space can be used to determine Coulomb-branch amplitudes to leading order in the mass. This is demonstrated in numerous examples. 2) We find compact explicit expressions for several towers of tree-level amplitudes, including scattering of two massive W-bosons with any number of positive helicity gluons, valid for all values of the mass. 3) We present the general structure of superamplitudes on the Coulomb branch. For example, the n-point "MHV-band" superamplitude is proportional to a Grassmann polynomial of mixed degree 4 to 12, which is uniquely determined by supersymmetry. We find explicit tree-level superamplitudes for this MHV band and for other simple sectors of the theory. 4) Dual conformal generators are constructed, and we explore the dual conformal properties of the simplest massive amplitudes. Our compact expressions for amplitudes and superamplitudes should be of both theoretical and phenomenological interest; in particular the tree-level results carry over to truncations of the theory with less supersymmetry.Comment: 29 pages, 1 figur

    Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice

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    Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 (Atf4) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway

    Assessing copy number aberrations and copy neutral loss of heterozygosity across the genome as best practice: An evidence based review of clinical utility from the cancer genomics consortium (CGC) working group for myelodysplastic syndrome, myelodysplastic/myeloproliferative and myeloproliferative neoplasms

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    Multiple studies have demonstrated the utility of chromosomal microarray (CMA) testing to identify clinically significant copy number alterations (CNAs) and copy-neutral loss-of-heterozygosity (CN-LOH) in myeloid malignancies. However, guidelines for integrating CMA as a standard practice for diagnostic evaluation, assessment of prognosis and predicting treatment response are still lacking. CMA has not been recommended for clinical work-up of myeloid malignancies by the WHO 2016 or the NCCN 2017 guidelines but is a suggested test by the European LeukaemiaNet 2013 for the diagnosis of primary myelodysplastic syndrome (MDS). The Cancer Genomics Consortium (CGC) Working Group for Myeloid Neoplasms systematically reviewed peer-reviewed literature to determine the power of CMA in (1) improving diagnostic yield, (2) refining risk stratification, and (3) providing additional genomic information to guide therapy. In this manuscript, we summarize the evidence base for the clinical utility of array testing in the workup of MDS, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and myeloproliferative neoplasms (MPN). This review provides a list of recurrent CNAs and CN-LOH noted in this disease spectrum and describes the clinical significance of the aberrations and how they complement gene mutation findings by sequencing. Furthermore, for new or suspected diagnosis of MDS or MPN, we present suggestions for integrating genomic testing methods (CMA and mutation testing by next generation sequencing) into the current standard-of-care clinical laboratory testing (karyotype, FISH, morphology, and flow)

    Increased SBPase activity improves photosynthesis and grain yield in wheat grown in greenhouse conditions

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    To meet the growing demand for food, substantial improvements in yields are needed. This is particularly the case for wheat, where global yield has stagnated in recent years. Increasing photosynthesis has been identified as a primary target to achieve yield improvements. To increase leaf photosynthesis in wheat, the level of the Calvin-Benson cycle enzyme sedoheptulose-1,7-biphosphatase (SBPase) has been increased through transformation and expression of a Brachypodium dystachion SBPase gene construct. Transgenic lines with increased SBPase protein levels and activity were grown under greenhouse conditions and showed enhanced leaf photosynthesis and increased total biomass and dry seed yield. This showed the potential of improving yield potential by increasing leaf photosynthesis in a crop species such as wheat. The results are discussed with regards to future strategies for further improvement of photosynthesis in wheat.publishersversionPeer reviewe
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