2,376 research outputs found

    Should we welcome robot teachers?

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    Abstract Current uses of robots in classrooms are reviewed and used to characterise four scenarios: (s1) Robot as Classroom Teacher; (s2) Robot as Companion and Peer; (s3) Robot as Care-eliciting Companion; and (s4) Telepresence Robot Teacher. The main ethical concerns associated with robot teachers are identified as: privacy; attachment, deception, and loss of human contact; and control and accountability. These are discussed in terms of the four identified scenarios. It is argued that classroom robots are likely to impact children’s’ privacy, especially when they masquerade as their friends and companions, when sensors are used to measure children’s responses, and when records are kept. Social robots designed to appear as if they understand and care for humans necessarily involve some deception (itself a complex notion), and could increase the risk of reduced human contact. Children could form attachments to robot companions (s2 and s3), or robot teachers (s1) and this could have a deleterious effect on their social development. There are also concerns about the ability, and use of robots to control or make decisions about children’s behaviour in the classroom. It is concluded that there are good reasons not to welcome fully fledged robot teachers (s1), and that robot companions (s2 and 3) should be given a cautious welcome at best. The limited circumstances in which robots could be used in the classroom to improve the human condition by offering otherwise unavailable educational experiences are discussed

    Nrf2-mediated neuroprotection response to recurrent hypoglycemia is insufficient to prevent cognitive impairment in a rodent model of type 1 diabetes

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    It remains uncertain whether recurrent nonsevere hypoglycemia (Hypo) results in long-term cognitive impairment in type 1 diabetes (T1D). This study tested the hypothesis that specifically in the T1D state, Hypo leads to cognitive impairment via a pathological response to oxidative stress. Wild-type (Control) and nuclear factor–erythroid 2 p45–related factor 2 (Nrf2) null mice were studied. Eight groups of mice (Control and Nrf2−/− ± T1D and ± Hypo) were subject to recurrent, twice-weekly, insulin or saline injections over 4 weeks, after which cognitive function was assessed and brain tissue analyzed. Recurrent moderate hypoglycemia in T1D, but not Control, mice significantly impaired cognitive performance, and this was associated with hippocampal oxidative damage and inflammation despite an enhanced expression of Nrf2 and its target genes Hmox1 and Nqo1. In Nrf2−/− mice, both T1D and Hypo independently resulted in impaired cognitive performance, and this was associated with oxidative cell damage and marked inflammation. Together, these data suggest that Hypo induces an Nrf2-dependent antioxidant response in the hippocampus, which counteracts oxidative damage. However, in T1D, this neuroprotective mechanism is insufficient to prevent neuronal oxidative damage, resulting in chronic deficits in working and long-term memory.</jats:p

    Spatial and temporal variability of biogenic isoprene emissions from a temperate estuary

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    [1] Isoprene is important for its atmospheric impacts and the ecophysiological benefits it affords to emitting organisms; however, isoprene emissions from marine systems remain vastly understudied compared to terrestrial systems. This study investigates for the first time drivers of isoprene production in a temperate estuary, and the role this production may play in enabling organisms to tolerate the inherently wide range of environmental conditions. Intertidal sediment cores as well as high and low tide water samples were collected from four sites along the Colne Estuary, UK, every six weeks over a year. Isoprene concentrations in the water were significantly higher at low than high tide, and decreased toward the mouth of the estuary; sediment production showed no spatial variability. Diel isoprene concentration increased with light availability and decreased with tidal height; nighttime production was 79% lower than daytime production. Seasonal isoprene production and water concentrations were highest for the warmest months, with production strongly correlated with light (r2 = 0.800) and temperature (r2 = 0.752). Intertidal microphytobenthic communities were found to be the primary source of isoprene, with tidal action acting as a concentrating factor for isoprene entering the water column. Using these data we estimated an annual production rate for this estuary of 681 μmol m−2 y−1. This value falls at the upper end of other marine estimates and highlights the potentially significant role of estuaries as isoprene sources. The control of estuarine isoprene production by environmental processes identified here further suggests that such emissions may be altered by future environmental change

    A combined in vitro/in silico approach to identifying off-target receptor toxicity

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    Many xenobiotics can bind to off-target receptors and cause toxicity via the dysregulation of downstream transcription factors. Identification of subsequent off-target toxicity in these chemicals has often required extensive chemical testing in animal models. An alternative, integrated in vitro/in silico approach for predicting toxic off-target functional responses is presented to refine in vitro receptor identification and reduce the burden on in vivo testing. As part of the methodology, mathematical modelling is used to mechanistically describe processes that regulate transcriptional activity following receptor-ligand binding informed by transcription factor signalling assays. Critical reactions in the signalling cascade are identified to highlight potential perturbation points in the biochemical network that can guide and optimise additional in vitro testing. A physiologically-based pharmacokinetic model provides information on the timing and localisation of different levels of receptor activation informing whole-body toxic potential resulting from off-target binding

    Medication use by middle-aged and older participants of an exercise study: results from the Brain in Motion study

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    BACKGROUND: Over the past 50 years, there has been an increase in the utilization of prescribed, over-the-counter (OTC) medications, and natural health products. Although it is known that medication use is common among older persons, accurate data on the patterns of use, including the quantity and type of medications consumed in a generally healthy older population from a Canadian perspective are lacking. In this study, we study the pattern of medication use in a sedentary but otherwise healthy older persons use and determined if there was an association between medication use and aerobic fitness level. METHODS: All participants enrolled in the Brain in Motion study provided the name, formulation, dosage and frequency of any medications they were consuming at the time of their baseline assessment. Maximal aerobic capacity (VO(2)max) was determined on each participant. RESULTS: Two hundred seventy one participants (mean age 65.9 ± 6.5 years; range 55–92; 54.6% females) were enrolled. Most were taking one or more (1+) prescribed medication (n = 204, 75.3%), 1+ natural health product (n = 221, 81.5%) and/or 1+ over-the-counter (OTC) drug (n = 174, 64.2%). The most commonly used prescribed medications were HMG-CoA reductase inhibitors (statins) (n = 52, 19.2%). The most common natural health product was vitamin D (n = 201, 74.2%). For OTC drugs, non-steroidal anti-inflammatories (n = 82, 30.3%) were the most common. Females were more likely than males to take 1+ OTC medications, as well as supplements. Those over 65 years of age were more likely to consume prescription drugs than their counterparts (p ≤ 0.05). Subjects taking more than two prescribed or OTC medications were less physically fit as determined by their VO(2)max. The average daily Vitamin D intake was 1896.3 IU per participant. CONCLUSIONS: Medication use was common in otherwise healthy older individuals. Consumption was higher among females and those older than 65 years. Vitamin D intake was over two-fold higher than the recommended 800 IU/day for older persons, but within the tolerable upper intake of 4,000 IU/day. The appropriateness of the high rate of medication use in this generally healthy population deserves further investigation

    Relation of delayed recovery of myocardial function after takotsubo cardiomyopathy to subsequent quality of life

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    Takotsubo cardiomyopathy (TTC) has generally been regarded as a relatively transient disorder, characterized by reversible regional left ventricular systolic dysfunction. However, most patients with TTC experience prolonged lassitude or dyspnea after acute attacks. Although this might reflect continued emotional stress, myocardial inflammation and accentuated brain-type natriuretic peptide (BNP) release persist for at least 3 months. We therefore tested the hypotheses that this continued inflammation is associated with (1) persistent contractile dysfunction and (2) consequent impairment of quality of life. Echocardiographic parameters (global longitudinal strain [GLS], longitudinal strain rate [LSR], and peak apical twist [AT]) were compared acutely and after 3 months in 36 female patients with TTC and 19 age-matched female controls. Furthermore, correlations were sought between putative functional anomalies, inflammatory markers (T2 score on cardiovascular magnetic resonance, plasma NT-proBNP, and high-sensitivity C-reactive protein levels), and the physical composite component of SF36 score (SF36-PCS). In TTC cases, left ventricular ejection fraction returned to normal within 3 months. GLS, LSR, and AT improved significantly over 3-month recovery, but GLS remained reduced compared to controls even at follow-up (-17.9 ± 3.1% vs -20.0 ± 1.8%, p = 0.003). Impaired GLS at 3 months was associated with both persistent NT-proBNP elevation (p = 0.03) and reduced SF36-PCS at ≥3 months (p = 0.04). In conclusion, despite normalization of left ventricular ejection fraction, GLS remains impaired for at least 3 months, possibly as a result of residual myocardial inflammation. Furthermore, perception of impaired physical exercise capacity ≥3 months after TTC may be explained by persistent myocardial dysfunction

    Ganetespib in combination with pemetrexed-platinum chemotherapy in patients with pleural Mesothelioma (MESO-02): A phase Ib trial

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    Purpose: Ganetespib, a highly potent, small-molecule Heatshock protein 90 inhibitor, has potential efficacy in malignant pleural mesothelioma (MPM) via activity on critical survival pathways and known synergies with antifolates and platinum chemotherapy. We conducted a dose-escalation study to identify the maximum tolerated dose (MTD) of ganetespib in patients with chemotherapy-naïve MPM. Patients and Methods: MESO-02 (ClinicalTrials.gov: NCT01590160) was a nonrandomized, multicenter, phase Ib trial of 3-weekly ganetespib (100 mg/m2, 150 mg/m2, 200 mg/m2; days 1 and 15) with pemetrexed (500 mg/m2; day 1) and cisplatin (75 mg/m2; day 1) or carboplatin (area under concentration–time curve 5; day 1) in patients with MPM. Dose escalation was performed using the 3 + 3 design (cisplatin) and accelerated titration design (carboplatin). Secondary endpoints included best response, progression-free survival (PFS), and pharmacogenomic analyses. Results: Of 27 patients enrolled (cisplatin, n = 16; carboplatin, n = 11), 3 experienced dose-limiting toxicities: grade 3 nausea (cisplatin, n = 1; carboplatin, n = 1) and grade 2 infusion-related reaction (carboplatin, n = 1). Ganetespib's MTD was 200 mg/m2. Partial response was observed in 14 of 27 patients (52%; 61% in 23 response-evaluable patients) and 13 of 21 (62%) with epithelioid histology. At the MTD, 10 of 18 patients (56%) had partial response, 15 of 18 (83%) had disease control, and median PFS was 6.3 months (95% CI, 5.0–10.0). One responder exhibited disease control beyond 50 months. Global loss of heterozygosity was associated with shorter time to progression (HR 1.12; 95% CI, 1.02–1.24; P = 0.018). Conclusions: Ganetespib can be combined safely with pemetrexed and platinum chemotherapy to treat patients with MPM. This class of agent should be investigated in larger randomized studies

    Children's age influences their use of biological and mechanical questions towards a humanoid

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    Complex autonomous interactions, biomimetic appearances, and responsive behaviours are increasingly seen in social robots. These features, by design or otherwise, may substantially influence young children’s beliefs of a robot’s animacy. Young children are believed to hold naive theories of animacy, and can miscategorise objects as living agents with intentions; however, this develops with age to a biological understanding. Prior research indicates that children frequently categorise a responsive humanoid as being a hybrid of person and machine; although, with age, children tend towards classifying the humanoid as being more machine-like. Our current research explores this phenomenon, using an unobtrusive method: recording childrens conversational interaction with the humanoid and classifying indications of animacy beliefs in childrens questions asked. Our results indicate that established findings are not an artefact of prior research methods: young children tend to converse with the humanoid as if it is more animate than older children do

    Temporal changes in tau phosphorylation and related kinase and phosphatases following two models of traumatic brain injury

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    Published: November 09, 2018A history of traumatic brain injury (TBI) is linked to later neurodegeneration, with a key feature accumulation of hyperphosphorylated tau. Tau is a microtubule stability protein that undergoes frequent cycles of phosphorylation and dephosphorylation due to kinases and phosphatase activity. Hyperphosphorylation of tau destabilizes microtubules interrupting axonal transport, as well as promotes aggregation disturbing synaptic dysfunction. Aberrant phosphorylation of tau post-injury is thought to be a key player in later neurodegeneration. However, it is not known whether type of TBI- a single severe injury compared to repeated mild injuries- affects the time course of tau accumulation or the pattern of changes in kinases and phosphatases that facilitate this phosphorylation. To investigate, male Sprague Dawley rats were subjected to either a single moderate/severe or 3 mild TBIs spaced 5 days apart (rmTBI) utlising the Marmarou impact-acceleration model. Levels of cortical ptau (AT180, pSer422, oligomeric tau), pGSK3β, pCDK5, pERK1/2, pAkt and PP2Ac were evaluated at 24h, 7 days, 1 month and 3 months post-injury, with changes in tau phosphorylation confirmed via immunohistochemistry. A similar time course of AT180 tau phosphorylation was seen irrespective of the nature of the initiating insult, with a spike at 24h post-injury return to baseline and then increasing chronically at 3 months post-injury. In line with this, levels of PP2Ac were decreased at 24h and 3 months post-injury, indicating a potential loss of phosphatase activity. Interestingly, minimal changes were seen in the kinases examined, with a spike in phosphorylation of GSK3β, at the inhibitory Ser site, at 24h and 3 months following rmTBI, but not single moderate severe TBI, suggesting a possible protective effect only post-rmTBI. This study highlights that changes in levels of phosphorylated tau are similar, regardless of the initiating injury, and highlights the need to further understand the driving mechanisms behind this phenomenon.Lyndsey Collins-Praino, Daniel Gutschmidt, Jessica Sharkey, Alina Arulsamy, and Frances Corriga
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