266 research outputs found

    A method for generating an illusion of backwards time travel using immersive virtual reality—an exploratory study

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    We introduce a new method, based on immersive virtual reality (IVR), to give people the illusion of having traveled backwards through time to relive a sequence of events in which they can intervene and change history. The participant had played an important part in events with a tragic outcome—deaths of strangers—by having to choose between saving 5 people or 1. We consider whether the ability to go back through time, and intervene, to possibly avoid all deaths, has an impact on how the participant views such moral dilemmas, and also whether this experience leads to a re-evaluation of past unfortunate events in their own lives. We carried out an exploratory study where in the “Time Travel” condition 16 participants relived these events three times, seeing incarnations of their past selves carrying out the actions that they had previously carried out. In a “Repetition” condition another 16 participants replayed the same situation three times, without any notion of time travel. Our results suggest that those in the Time Travel condition did achieve an illusion of “time travel” provided that they also experienced an illusion of presence in the virtual environment, body ownership, and agency over the virtual body that substituted their own. Time travel produced an increase in guilt feelings about the events that had occurred, and an increase in support of utilitarian behavior as the solution to the moral dilemma. Time travel also produced an increase in implicit morality as judged by an implicit association test. The time travel illusion was associated with a reduction of regret associated with bad decisions in their own lives. The results show that when participants have a third action that they can take to solve the moral dilemma (that does not immediately involve choosing between the 1 and the 5) then they tend to take this option, even though it is useless in solving the dilemma, and actually results in the deaths of a greater number

    Child's Play? Children and Young People's Resistances to Domestic Violence and Abuse

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    Children and young people's (CYP) space to play can be constrained in families affected by domestic violence and abuse (DVA), potentially impacting their development. Play also has the potential to strengthen CYP's capacity to resist controlling and abusive dynamics in the family. Interviews were conducted with 107 CYP aged 8–18, and were analysed using interpretive interactionism. Three themes relevant to children's experiences of play were identified: Play and Coercive Control; Play Re‐makes the World and Play and Relationality. This article highlights the potential for play to enable children to retain a sense of relational connectedness and agency, despite violence and control; we argue for more opportunities for children to play away from the gaze of adults and advocate for more dedicated services for families who experience DVA

    Pupillometry and P3 index the locus coeruleus– noradrenergic arousal function in humans

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    The adaptive gain theory highlights the pivotal role of the locus coeruleus–noradrenergic (LC-NE) system in regulating task engagement. In humans, however, LC-NE functional dynamics remain largely unknown. We evaluated the utility of two candidate psychophysiological markers of LC-NE activity: the P3 event-related potential and pupil diameter. Electroencephalogram and pupillometry data were collected from 24 participants who performed a 37-min auditory oddball task. As predicted by the adaptive gain theory, prestimulus pupil diameter exhibited an inverted U-shaped relationship to P3 and task performance such that largest P3 amplitudes and optimal performance occurred at the same intermediate level of pupil diameter. Large phasic pupil dilations, by contrast, were elicited during periods of poor performance and were followed by reengagement in the task and increased P3 amplitudes. These results support recent proposals that pupil diameter and the P3 are sensitive to LC-NE mode

    The Dozen Things Experimental Economists Should Do (More of)

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    What was once broadly viewed as an impossibility—learning from experimental data in economics—has now become commonplace. Governmental bodies, think tanks, and corporations around the world employ teams of experimental researchers to answer their most pressing questions. For their part, in the past two decades academics have begun to more actively partner with organizations to generate data via field experimentation. Although this revolution in evidence‐based approaches has served to deepen the economic science, recently a credibility crisis has caused even the most ardent experimental proponents to pause. This study takes a step back from the burgeoning experimental literature and introduces 12 actions that might help to alleviate this credibility crisis and raise experimental economics to an even higher level. In this way, we view our “12 action wish list” as discussion points to enrich the field

    SOS Response Induces Persistence to Fluoroquinolones in Escherichia coli

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    Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be an important factor influencing the outcome of antibiotic therapy in vivo

    Leopard syndrome

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    LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4–5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS), chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should address growth and motor development and congenital anomalies, in particular cardiac defects that should be monitored annually. Hypertrophic cardiomyopathy needs careful risk assessment and prophylaxis against sudden death in patients at risk. Hearing should be evaluated annually until adulthood. With the only exception of ventricular hypertrophy, adults with LS do not require special medical care and long-term prognosis is favourable

    Measuring Health Utilities in Children and Adolescents: A Systematic Review of the Literature.

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    BACKGROUND: The objective of this review was to evaluate the use of all direct and indirect methods used to estimate health utilities in both children and adolescents. Utilities measured pre- and post-intervention are combined with the time over which health states are experienced to calculate quality-adjusted life years (QALYs). Cost-utility analyses (CUAs) estimate the cost-effectiveness of health technologies based on their costs and benefits using QALYs as a measure of benefit. The accurate measurement of QALYs is dependent on using appropriate methods to elicit health utilities. OBJECTIVE: We sought studies that measured health utilities directly from patients or their proxies. We did not exclude those studies that also included adults in the analysis, but excluded those studies focused only on adults. METHODS AND FINDINGS: We evaluated 90 studies from a total of 1,780 selected from the databases. 47 (52%) studies were CUAs incorporated into randomised clinical trials; 23 (26%) were health-state utility assessments; 8 (9%) validated methods and 12 (13%) compared existing or new methods. 22 unique direct or indirect calculation methods were used a total of 137 times. Direct calculation through standard gamble, time trade-off and visual analogue scale was used 32 times. The EuroQol EQ-5D was the most frequently-used single method, selected for 41 studies. 15 of the methods used were generic methods and the remaining 7 were disease-specific. 48 of the 90 studies (53%) used some form of proxy, with 26 (29%) using proxies exclusively to estimate health utilities. CONCLUSIONS: Several child- and adolescent-specific methods are still being developed and validated, leaving many studies using methods that have not been designed or validated for use in children or adolescents. Several studies failed to justify using proxy respondents rather than administering the methods directly to the patients. Only two studies examined missing responses to the methods administered with respect to the patients' ages

    Cell-autonomous and environmental contributions to the interstitial migration of T cells

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    A key to understanding the functioning of the immune system is to define the mechanisms that facilitate directed lymphocyte migration to and within tissues. The recent development of improved imaging technologies, most prominently multi-photon microscopy, has enabled the dynamic visualization of immune cells in real-time directly within intact tissues. Intravital imaging approaches have revealed high spontaneous migratory activity of T cells in secondary lymphoid organs and inflamed tissues. Experimental evidence points towards both environmental and cell-intrinsic cues involved in the regulation of lymphocyte motility in the interstitial space. Based on these data, several conceptually distinct models have been proposed in order to explain the coordination of lymphocyte migration both at the single cell and population level. These range from “stochastic” models, where chance is the major driving force, to “deterministic” models, where the architecture of the microenvironment dictates the migratory trajectory of cells. In this review, we focus on recent advances in understanding naïve and effector T cell migration in vivo. In addition, we discuss some of the contradictory experimental findings in the context of theoretical models of migrating leukocytes

    Genetic variability in response to amyloid beta deposition influences Alzheimer's disease risk

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    Genome-wide association studies of late-onset Alzheimer’s disease risk have previously identified genes primarily expressed in microglia that form a transcriptional network. Using transgenic mouse models of amyloid deposition we previously showed that many of the mouse orthologues of these risk genes are co-expressed and associated with amyloid pathology. In this new study, we generate an improved RNA-seq-derived network that is expressed in amyloid-responsive mouse microglia and we statistically compare this with gene-level variation in previous human Alzheimer’s disease genome-wide association study to predict at least four new risk genes for the disease (OAS1, LAPTM5, ITGAM/CD11b and LILRB4). Of the mouse orthologues of these genes Oas1a is likely to respond directly to amyloid at the transcriptional level, similarly to established risk gene Trem2, because the increase in Oas1a and Trem2 transcripts in response to amyloid deposition in transgenic mice is significantly higher than both the increase of the average microglial transcript and the increase in microglial number. In contrast, the mouse orthologues of LAPTM5, ITGAM/CD11b and LILRB4 (Laptm5, Itgam/CD11b and Lilra5) show increased transcripts in the presence of amyloid plaques similar in magnitude to the increase of the average microglial transcript and the increase in microglia number, except that Laptm5 and Lilra5 transcripts increase significantly quicker than the average microglial transcript as the plaque load becomes dense. This work suggests that genetic variability in the microglial response to amyloid deposition is a major determinant for Alzheimer’s disease risk, and identification of these genes may help to predict the risk of developing Alzheimer’s disease. These findings also provide further insights into the mechanisms underlying Alzheimer’s disease for potential drug discovery
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