251 research outputs found

    Temporal estimation in prediction motion tasks is biased by a moving destination

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    Β© 2018 The Authors. An ability to predict the time-to-contact (TTC) of moving objects that become momentarily hidden is advantageous in everyday life and could be particularly so in fast-ball sports. Prediction motion (PM) experiments have sought to test this ability using tasks where a disappearing target moves toward a stationary destination. Here, we developed two novel versions of the PM task in which the destination either moved away from (Chase) or toward (Attract) the moving target. The target and destination moved with different speeds such that collision occurred 750, 1,000 or 1,250 ms after target occlusion. To determine if domain-specific experience conveys an advantage in PM tasks, we compared the performance of different sporting groups ranging from internationally competing athletes to nonsporting controls. There was no difference in performance between sporting groups and non-sporting controls but there were significant and independent effects on response error by target speed, destination speed, and occlusion period. We simulated these findings using a revised version of the linear TTC model of response timing for PM tasks (Yakimoff, Bocheva, & Mitrania, 1987; Yakimoff, Mateeff, Ehrenstein, & Hohnsbein, 1993) in which retinal input from the moving destination biases the internal representation of the occluded target. This revision closely reproduced the observed patterns of response error and thus describes a means by which the brain might estimate TTC when the target and destination are in motion

    Phylogeography of Japanese encephalitis virus:genotype is associated with climate

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    The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

    Pain through the perspective of art and creativity: insights from the Unmasking Pain project

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    People struggle to tell their story of living with pain and when they do it is articulated in a way that may not be understood, heard or taken seriously. Unmasking Pain is an artist-led project that explored creative approaches to tell stories of life with pain. The project was led by a dance theatre company that specialises in storytelling and emotional experiences for players and audiences. The project involved artists and people living with ongoing pain co-creating activities and environments to curiously explore "oneself", through imagination and creative expression. This article discusses insights and perspectives emerging from the project. The project revealed the power of art to make-sense of oneself with or without pain, and how art facilitates expression of complex inner experience and personal stories. People described Unmasking Pain as "explorative joy despite pain", and "a new set of rules" that contrasts with those experienced during clinical encounters. We discuss how art has the potential to improve clinical encounters and promote health and well-being, and whether artist-led activities are an intervention, therapy, or something else. Pain rehabilitation specialists from the project described Unmasking Pain as "freeing-up thinking", allowing conceptual thought beyond the biopsychosocial model of pain. We conclude that art has the potential to shift people living with pain from "I can't do, I am not willing to do it" to "Perhaps I can, I'll give it a go, I enjoyed"

    Neurospora from natural populations: Population genomics insights into the Life history of a model microbial Eukaryote

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    The ascomycete filamentous fungus Neurospora crassa played a historic role in experimental biology and became a model system for genetic research. Stimulated by a systematic effort to collect wild strains initiated by Stanford geneticist David Perkins, the genus Neurospora has also become a basic model for the study of evolutionary processes, speciation, and population biology. In this chapter, we will first trace the history that brought Neurospora into the era of population genomics. We will then cover the major contributions of population genomic investigations using Neurospora to our understanding of microbial biogeography and speciation, and review recent work using population genomics and genome-wide association mapping that illustrates the unique potential of Neurospora as a model for identifying the genetic basis of (potentially adaptive) phenotypes in filamentous fungi. The advent of population genomics has contributed to firmly establish Neurospora as a complete model system and we hope our review will entice biologists to include Neurospora in their research

    Unidimensional scales for fears of cancer recurrence and their psychometric properties : the FCR4 and FCR7

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    Funding: Support was received from SUPAC (NCRI) Early Career Fund to complete this study. NCRI Supportive & Palliative Care (SuPaC) Research Collaboratives Capacity Building Grant Scheme: G Ozakinci (PI), G Humphris, M Sharpe.Background:Β  The assessment of fear of recurrence (FCR) is crucial for understanding an important psychological state in patients diagnosed and treated for cancer. The study aim was to determine psychometric details of a seven question self-report scale (FCR7) and a short form (FCR4) based upon items already used in various extensive measures of FCR. Methods:Β  Two consecutive samples of patients (breast and colorectal) were recruited from a single specialist cancer centre. The survey instrument contained the FCR7 items, Hospital Anxiety and Depression Scale (HADS), and demographic details. Clinical information was obtained from patient hospital records. Statistical analyses were performed using classical test and item response theory approaches, to demonstrate unidimensional factor structure and testing key parameters. Construct validity was inspected through nomological and theoretical prediction. Results:Β  Internal consistency was demonstrated by alpha coefficients (FCR4: 0.93 and FCR7: 0.92). Both scales (FCR7 & FCR4) were associated with the HADs subscales as predicted. Patients who experienced chemotherapy, minor aches/pains, thought avoidance of cancer and high cancer risk belief were more fearful. Detailed inspection of item responses profile provided some support for measurement properties of scales. Conclusion: The internal consistency, and pattern of key associations and discriminability indices provided positive psychometric evidence for these scales. The brief measures of FCR may be considered for audit, screening or routine use in clinical service and research investigations.Publisher PDFPeer reviewe

    Bramwell-Hill modeling for local aortic pulse wave velocity estimation: a validation study with velocity-encoded cardiovascular magnetic resonance and invasive pressure assessment

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    <p>Abstract</p> <p>Background</p> <p>The Bramwell-Hill model describes the relation between vascular wall stiffness expressed in aortic distensibility and the pulse wave velocity (PWV), which is the propagation speed of the systolic pressure wave through the aorta. The main objective of this study was to test the validity of this model locally in the aorta by using PWV-assessments based on in-plane velocity-encoded cardiovascular magnetic resonance (CMR), with invasive pressure measurements serving as the gold standard.</p> <p>Methods</p> <p>Seventeen patients (14 male, 3 female, mean age Β± standard deviation = 57 Β± 9 years) awaiting cardiac catheterization were prospectively included. During catheterization, intra-arterial pressure measurements were obtained in the aorta at multiple locations 5.8 cm apart. PWV was determined regionally over the aortic arch and locally in the proximal descending aorta. Subsequently, patients underwent a CMR examination to measure aortic PWV and aortic distention. Distensibility was determined locally from the aortic distension at the proximal descending aorta and the pulse pressure measured invasively during catheterization and non-invasively from brachial cuff-assessment. PWV was determined regionally in the aortic arch using through-plane and in-plane velocity-encoded CMR, and locally at the proximal descending aorta using in-plane velocity-encoded CMR. Validity of the Bramwell-Hill model was tested by evaluating associations between distensibility and PWV. Also, theoretical PWV was calculated from distensibility measurements and compared with pressure-assessed PWV.</p> <p>Results</p> <p>In-plane velocity-encoded CMR provides stronger correlation (p = 0.02) between CMR and pressure-assessed PWV than through-plane velocity-encoded CMR (r = 0.69 versus r = 0.26), with a non-significant mean error of 0.2 Β± 1.6 m/s for in-plane versus a significant (p = 0.006) error of 1.3 Β± 1.7 m/s for through-plane velocity-encoded CMR. The Bramwell-Hill model shows a significantly (p = 0.01) stronger association between distensibility and PWV for local assessment (r = 0.8) than for regional assessment (r = 0.7), both for CMR and for pressure-assessed PWV. Theoretical PWV is strongly correlated (r = 0.8) with pressure-assessed PWV, with a statistically significant (p = 0.04) mean underestimation of 0.6 Β± 1.1 m/s. This theoretical PWV-estimation is more accurate when invasively-assessed pulse pressure is used instead of brachial cuff-assessment (p = 0.03).</p> <p>Conclusions</p> <p>CMR with in-plane velocity-encoding is the optimal approach for studying Bramwell-Hill associations between local PWV and aortic distensibility. This approach enables non-invasive estimation of local pulse pressure and distensibility.</p

    A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days

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    Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39–73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2–5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer

    How to do an evaluation: pitfalls and traps

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    The recent literature is replete with papers evaluating computational tools (often those operating on 3D structures) for their performance in a certain set of tasks. Most commonly these papers compare a number of docking tools for their performance in cognate re-docking (pose prediction) and/or virtual screening. Related papers have been published on ligand-based tools: pose prediction by conformer generators and virtual screening using a variety of ligand-based approaches. The reliability of these comparisons is critically affected by a number of factors usually ignored by the authors, including bias in the datasets used in virtual screening, the metrics used to assess performance in virtual screening and pose prediction and errors in crystal structures used

    How to do an evaluation: pitfalls and traps

    Get PDF
    The recent literature is replete with papers evaluating computational tools (often those operating on 3D structures) for their performance in a certain set of tasks. Most commonly these papers compare a number of docking tools for their performance in cognate re-docking (pose prediction) and/or virtual screening. Related papers have been published on ligand-based tools: pose prediction by conformer generators and virtual screening using a variety of ligand-based approaches. The reliability of these comparisons is critically affected by a number of factors usually ignored by the authors, including bias in the datasets used in virtual screening, the metrics used to assess performance in virtual screening and pose prediction and errors in crystal structures used

    Do women β©Ύ50 years of age need as much screening as women <50 years after they have had negative screening results?

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    To assess the adequacy of a routine screening to identify cervical intraepithelial neoplasia 2 or worse (CIN2+) in women over 50 years of age, a retrospective cohort was set in six Italian organised population-based screening programmes. In all, 287 330 women (1 714 550 person-years of observation, 1110 cases) screened at age 25–64, with at least two cytological screening tests, the first negative, were followed from their first negative smear until a biopsy proven CIN2+ lesion or their last negative smear. For women aged 25–49 and 50–64 years, crude and age-standardised detection rate (DR), cumulative risk (CR), adjusted hazard risk for number of previous negative screens, probability of false-positive CIN2+ after two or more smear tests were calculated. Detection rate is significantly lower over 50 years of age. Multivariable analysis shows a significant protective effect from four screening episodes (DR=0.70, 95% CI: 0.51–0.97); the effect of age β©Ύ50 is 0.29 (95% CI: 0.24–0.35). The CR of CIN2+ is at least eightfold higher in women <50 (CR=2.06, 95% CI: 1.88–2.23) after one previous negative test than in women β©Ύ50 years with four screens (CR=0.23, 95% CI: 0.00–0.46). Over 50 years of age, after four tests at least three false-positive cases are diagnosed for every true positive. Benefits arising from cytological screening is uncertain in well-screened older women
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