1,702 research outputs found

    Positive Education in the United Arab Emirates: Navigating Through and Beyond the Global Pandemic

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    Drawing on data from the emirate of Ras Al Khaimah (RAK) in the UAE, this study looks at using Positive Education (PE) to build strengths, competencies, well-being, and toughness in educational communities, to combat learning loss before and during the pandemic. We were interested in understanding how educational leaders, teachers, and students perceive PE and its impact on student well-being, as well as how well-equipped they were to handle the effects of the pandemic after participating in PE. Using qualitative data from semi-structured in-person interviews, focus groups, classroom observations, and document analysis, this study argues that PE supported students in coping with stressors associated with the pandemic. We show three significant findings. First, we found that the pandemic impacted student well-being in numerous academic and nonacademic ways. Second, our results demonstrate that PE was helpful in supporting student resilience and well-being during the pandemic. Third, data show that because PE was rolled out just before the pandemic began, the pandemic curtailed its full implementation. We conclude by recommending a whole school approach to PE that includes family members since the pandemic revealed that when students are engaged in remote learning or otherwise not face-to-face at school, it is critical that parents/families can support youth who may be struggling. Finally, we note the need for school-based support, like PE, to engender student resiliency

    Polarization of macrophages toward M2 phenotype is favored by reduction in iPLA2β (group VIA phospholipase A2)*

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    Macrophages are important in innate and adaptive immunity. Macrophage participation in inflammation or tissue repair is directed by various extracellular signals and mediated by multiple intracellular pathways. Activation of group VIA phospholipase A2 (iPLA2β) causes accumulation of arachidonic acid, lysophospholipids, and eicosanoids that can promote inflammation and pathologic states. We examined the role of iPLA2β in peritoneal macrophage immune function by comparing wild type (WT) and iPLA2β−/− mouse macrophages. Compared with WT, iPLA2β−/− macrophages exhibited reduced proinflammatory M1 markers when classically activated. In contrast, anti-inflammatory M2 markers were elevated under naïve conditions and induced to higher levels by alternative activation in iPLA2β−/− macrophages compared with WT. Induction of eicosanoid (12-lipoxygenase (12-LO) and cyclooxygenase 2 (COX2))- and reactive oxygen species (NADPH oxidase 4 (NOX4))-generating enzymes by classical activation pathways was also blunted in iPLA2β−/− macrophages compared with WT. The effects of inhibitors of iPLA2β, COX2, or 12-LO to reduce M1 polarization were greater than those to enhance M2 polarization. Certain lipids (lysophosphatidylcholine, lysophosphatidic acid, and prostaglandin E2) recapitulated M1 phenotype in iPLA2β−/− macrophages, but none tested promoted M2 phenotype. These findings suggest that (a) lipids generated by iPLA2β and subsequently oxidized by cyclooxygenase and 12-LO favor macrophage inflammatory M1 polarization, and (b) the absence of iPLA2β promotes macrophage M2 polarization. Reducing macrophage iPLA2β activity and thereby attenuating macrophage M1 polarization might cause a shift from an inflammatory to a recovery/repair milieu

    Io's polar volcanic thermal emission indicative of magma ocean and shallow tidal heating models

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    The distribution of Io's volcanic activity likely reflects the position and magnitude of internal tidal heating. We use new observations of Io's polar regions by the Juno spacecraft Jovian Infrared Auroral Mapper (JIRAM) to complete near-infrared global coverage, revealing the global distribution and magnitude of thermal emission from Io's currently erupting volcanoes. We show that the distribution of volcanic heat flow from 266 active hot spots is consistent with the presence of a global magma ocean, and/or shallow asthenospheric heating. We find that Io's polar volcanoes are less energetic but about the same in number per unit area than at lower latitudes. We also find that volcanic heat flow in the north polar cap is greater than that in the south. The low volcanic advection seen at Io's poles is therefore at odds with measurements of background temperature showing Io's poles are anomalously warm. We suggest that the differences in volcanic thermal emission from Io's poles compared to that at lower latitudes is indicative of lithospheric dichotomies that inhibit volcanic advection towards Io's poles, particularly in the south polar region.Comment: 17 pages, two tables, 7 figure

    Influence of Crohn’s disease related polymorphisms in innate immune function on ileal microbiome

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    We have previously identified NOD2 genotype and inflammatory bowel diseases (IBD) phenotype, as associated with shifts in the ileal microbiome (“dysbiosis”) in a patient cohort. Here we report an integrative analysis of an expanded number of Crohn's disease (CD) related genetic defects in innate immune function (NOD2, ATG16L1, IRGM, CARD9, XBP1, ORMDL3) and composition of the ileal microbiome by combining the initial patient cohort (Batch 1, 2005–2010, n = 165) with a second consecutive patient cohort (Batch 2, 2010–2012, n = 118). These combined patient cohorts were composed of three non-overlapping phenotypes: 1.) 106 ileal CD subjects undergoing initial ileocolic resection for diseased ileum, 2.) 88 IBD colitis subjects without ileal disease (predominantly ulcerative colitis but also Crohn’s colitis and indeterminate colitis, and 3.) 89 non-IBD subjects. Significant differences (FDR C. difficile infection, and NOD2 genotype on ileal dysbiosis in the expanded analysis. The relative abundance of the Proteobacteria phylum was positively associated with ileal CD and colitis phenotypes, but negatively associated with NOD2R genotype. Additional associations with ORMDL3 and XBP1 were detected at the phylum/subphylum level. IBD medications, such as immunomodulators and anti-TNFα agents, may have a beneficial effect on reversing dysbiosis associated with the IBD phenotype. Exploratory analysis comparing microbial composition of the disease unaffected region of the resected ileum between 27 ileal CD patients who subsequently developed endoscopic recurrence within 6–12 months versus 34 patients who did not, suggested that microbial biomarkers in the resected specimen helped stratify patients with respect to risk of post-surgical recurrence.</div

    Exploring white matter microstructural alterations in mild cognitive impairment: a multimodal diffusion MRI investigation utilizing diffusion kurtosis and free-water imaging

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    BackgroundMild Cognitive Impairment (MCI) is a transitional stage from normal aging to dementia, characterized by noticeable changes in cognitive function that do not significantly impact daily life. Diffusion MRI (dMRI) plays a crucial role in understanding MCI by assessing white matter integrity and revealing early signs of axonal degeneration and myelin breakdown before cognitive symptoms appear.MethodsThis study utilized the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to compare white matter microstructure in individuals with MCI to cognitively normal (CN) individuals, employing advanced dMRI techniques such as diffusion kurtosis imaging (DKI), mean signal diffusion kurtosis imaging (MSDKI), and free water imaging (FWI).ResultsAnalyzing data from 55 CN subjects and 46 individuals with MCI, this study found significant differences in white matter integrity, particularly in free water levels and kurtosis values, suggesting neuroinflammatory responses and microstructural integrity disruption in MCI. Moreover, negative correlations between Mini-Mental State Examination (MMSE) scores and free water levels in the brain within the MCI group point to the potential of these measures as early biomarkers for cognitive impairment.ConclusionIn conclusion, this study demonstrates how a multimodal advanced diffusion imaging approach can uncover early microstructural changes in MCI, offering insights into the neurobiological mechanisms behind cognitive decline

    Fuel cycle modelling of open cycle thorium-fuelled nuclear energy systems

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    In this study, we have sought to determine the advantages, disadvantages, and viability of open cycle thorium–uranium-fuelled (Th–U-fuelled) nuclear energy systems. This has been done by assessing three such systems, each of which requires uranium enriched to ∼20% 235U, in comparison to a reference uranium-fuelled (U-fuelled) system over various performance indicators, spanning material flows, waste composition, economics, and proliferation resistance. The values of these indicators were determined using the UK National Nuclear Laboratory’s fuel cycle modelling code ORION. This code required the results of lattice-physics calculations to model the neutronics of each nuclear energy system, and these were obtained using various nuclear reactor physics codes and burn-up routines. In summary, all three Th–U-fuelled nuclear energy systems required more separative work capacity than the equivalent benchmark U-fuelled system, with larger levelised fuel cycle costs and larger levelised cost of electricity. Although a reduction of ∼6% in the required uranium ore per kWh was seen for one of the Th–U-fuelled systems compared to the reference U-fuelled system, the other two Th–U-fuelled systems required more uranium ore per kWh than the reference. Negligible advantages and disadvantages were observed for the amount and the properties of the spent nuclear fuel (SNF) generated by the systems considered. Two of the Th–U-fuelled systems showed some benefit in terms of proliferation resistance of the SNF generated. Overall, it appears that there is little merit in incorporating thorium into nuclear energy systems operating with open nuclear fuel cycles

    Development of a Composite Measure of Product Adherence, Protocol Compliance, and Semen Exposure Using DNA and Protein Biomarkers for Topical HIV Prevention Studies

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    BackgroundPoor and inconsistent use of study products has hindered clinical HIV prevention studies. It is important to be able to monitor product adherence and protocol compliance in order to determine microbicide efficacy and safety more accurately. Current methods for monitoring adherence are subjective, non-specific, or invasive. Herein, we present a composite, objective measure of product adherence and protocol compliance to assess vaginal insertion, semen exposure and drug expulsion utilizing DNA, protein, and drug isolated directly from returned, vaginally used gel applicators.MethodsDNA, vaginal cells, and residual tenofovir were isolated from vaginally inserted applicators. Vaginal and semen biomarkers were amplified using a multiplex PCR to determine vaginal insertion. Vaginal cells were fixed followed by cytokeratin 4 immunocytochemistry to confirm DNA assessment of vaginal insertion. Tenofovir was extracted and quantitated through LC-MS/MS.ResultsDNA isolated from vaginally inserted applicators were positive for vaginal bacteria DNA and the control eukaryotic gene, amelogenin, while manually handled, “sham”, applicators were negative for both. Semen exposure was independently determined by simultaneous amplification of one or both Y-chromosomal genes, SRY and TSPY4. Vaginal insertion determination by DNA analysis was further confirmed by positive cytokeratin 4 (CK4) immunocytochemistry of vaginal cells remaining on the gel applicators. On the contrary, sham applicators provided very few cells when swabbed, and they were all negative for CK4. CK4 was not found in epidermal cells from the hand. Drug expulsion was detected through quantitation of residual gel present on the surface of returned applicators. Sham applicators had no detectable tenofovir.ConclusionUtilizing a composite, triple marker based panel of DNA, protein, and drug present on the surface of returned vaginal gel applicators, it is possible to determine, objectively and non-invasively, product adherence, protocol compliance, and semen exposure in microbicide trials

    Outcomes of a randomized controlled trial assessing a smartphone Application to reduce unmet needs among people diagnosed with CancEr (ACE)

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    © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Background: Smartphone technology represents an opportunity to deliver practical solutions for people affected by cancer at a scale that was previously unimaginable, such as information, appointment monitoring, and improved access to cancer support services. This study aimed to determine whether a smartphone application (app) reduced the unmet needs among people newly diagnosed with cancer. Methods: A single blind, multisite randomized controlled trial to determine the impact of an app-based, 4-month intervention. Newly diagnosed cancer patients were approached at three health service treatment clinics. Results: Eighty-two people were randomized (intervention; n = 43 and control; n = 39), average age was 59.5 years (SD: 12.9); 71% female; 67% married or in a de facto relationship. At baseline, there were no differences in participants’ characteristics between the groups. No significant effects, in reducing unmet needs, were demonstrated at the end of intervention (4-month) or 12-month follow-up. Overall, 94% used the app in weeks 1-4, which decreased to 41% in weeks 13-16. Mean app use time per participant: Cancer Information, 6.9 (SD: 18.9) minutes; Appointment Schedule, 5.1 (SD: 9.6) minutes; Cancer Services 1.5 minutes (SD: 6.8); Hospital Navigation, 1.4 (SD: 2.8) minutes. Conclusions: Despite consumer involvement in the design of this smartphone technology, the app did not reduce unmet needs. This may have been due to the study being underpowered. To contribute to a meaningful understanding and improved implementation of smartphone technology to support people affected by cancer, practical considerations, such as recruitment issues and access to, and confidence with, apps, need to be considered. Australian New Zealand Clinical Trials Registration (ACTRN) Trial Registration: 12616001251415; WEF 7/9/2016

    Aptamer-based multiplexed proteomic technology for biomarker discovery

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    Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

    Recruitment and follow-up of adolescent and young adult cancer survivors: the AYA HOPE Study

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    IntroductionCancer is rare in adolescents and young adults (AYA), but these patients have seen little improvement in survival in contrast to most other age groups. Furthermore, participation in research by AYAs is typically low. We conducted a study to examine the feasibility of recruiting a population-based sample of AYA survivors to examine issues of treatment and health outcomes.MethodsIndividuals diagnosed in 2007-08 and age 15-39 at the time of diagnosis with acute lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell cancer or sarcoma were identified by 7 Surveillance, Epidemiology, and End-Results (SEER) cancer registries, mailed surveys within 14 months after diagnosis and again a year later, and had medical records reviewed.Results525 (43%) of the eligible patients responded, 39% refused and 17% were lost to follow-up. Extensive efforts were required for most potential respondents (87%). 76% of respondents completed the paper rather than online survey version. In a multivariate model, age, cancer site, education and months from diagnosis to the first mailing of the survey were not associated with participation, although males (p  &lt;  0.01), Hispanics and non-Hispanic blacks (p  &lt;  0.001) were less likely to participate. 91% of survivors completing the initial survey completed the subsequent survey.DiscussionDespite the response rate, those who participated adequately reflected the population of AYA cancer survivors. The study demonstrates that cancer registries are valuable foundations for conducting observational, longitudinal population-based research on AYA cancer survivors.Implications for cancer survivorsAchieving a reasonable response rate in this population is possible, but requires extensive resources
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