1,761 research outputs found

    Reading sentences of uniform word length II: very rapid adaptation of the preferred saccade length

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    In the current study we investigated whether readers adjust their preferred saccade length (PSL) during reading on a trial-by-trial basis. The PSL refers to the distance between a saccade launch site and saccade target (i.e., the word center during reading) when participants neither undershoot nor overshoot this target (McConkie, Kerr, Reddix, & Zola, 1988). The tendency for saccades longer or shorter than the PSL to under or overshoot their target is referred to as the range error. Recent research by Cutter, Drieghe, and Liversedge (2017) has shown that the PSL changes to be shorter when readers are presented with thirty consecutive sentences exclusively made of three letter words, and longer when presented with thirty consecutive sentences exclusively made of five letter words. We replicated and extended this work by this time presenting participants with these uniform sentences in an unblocked design. We found that adaptation still occurred across different sentence types despite participants only having one trial to adapt. Our analyses suggested that this effect was driven by the length of the words readers were making saccades away from, rather than the length of the words in the rest of the sentence. We propose an account of the range error in which readers use parafoveal word length information to estimate the length of a saccade between the centre of two parafoveal words (termed the Centre-Based Saccade Length) prior to landing on the first of these words

    Integrating best practice and filling knowledge gaps in remote Aboriginal diabetes detection and care: Improving case detection and service delivery

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    This pilot project will provide detailed feedback on the results of previous studies to participating services. During discussions with clinic and management staff, barriers and enablers to implementing a new screening protocol using HbA1c testing will be determined. The project will also conduct a clinical systems and software / data quality needs assessment at participating sites, documenting strategies to improve diabetes programs and monitor short term changes resulting from the audit.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

    Variation in Base-Substitution Mutation in Experimental and Natural Lineages of Caenorhabditis Nematodes

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    Variation among lineages in the mutation process has the potential to impact diverse biological processes ranging from susceptibilities to genetic disease to the mode and tempo of molecular evolution. The combination of high-throughput DNA sequencing (HTS) with mutation-accumulation (MA) experiments has provided a powerful approach to genome-wide mutation analysis, though insights into mutational variation have been limited by the vast evolutionary distances among the few species analyzed. We performed a HTS analysis of MA lines derived from four Caenorhabditis nematode natural genotypes: C. elegans N2 and PB306 and C. briggsae HK104 and PB800. Total mutation rates did not differ among the four sets of MA lines. A mutational bias toward G:C→A:T transitions and G:C→T:A transversions was observed in all four sets of MA lines. Chromosome-specific rates were mostly stable, though there was some evidence for a slightly elevated X chromosome mutation rate in PB306. Rates were homogeneous among functional coding sequence types and across autosomal cores, arms, and tips. Mutation spectra were similar among the four MA line sets but differed significantly when compared with patterns of natural base-substitution polymorphism for 13/14 comparisons performed. Our findings show that base-substitution mutation processes in these closely related animal lineages are mostly stable but differ from natural polymorphism patterns in these two species

    Loss of DOK2 induces carboplatin resistance in ovarian cancer via suppression of apoptosis

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    Objective. Ovarian cancers are highly heterogeneous and while chemotherapy is the preferred treatment many patients are intrinsically resistant or quickly develop resistance. Furthermore, all tumors that recur ultimately become resistant. Recent evidence suggests that epigenetic deregulation may be a key factor in the onset and maintenance of chemoresistance. We set out to identify epigenetically silenced genes that affect chemoresistance. Methods. The epigenomes of a total of 45 ovarian samples were analyzed to identify epigenetically altered genes that segregate with platinum response, and further filtered with expression data to identify genes that were suppressed. A tissue culture carboplatin resistance screen was utilized to functionally validate this set of candidate platinum resistance genes. Results. Our screen correctly identified 19 genes that when suppressed altered the chemoresistance of the cells in culture. Of the genes identified in the screen we further characterized one gene, docking protein 2 (DOK2), an adapter protein downstream of tyrosine kinase, to determine if we could elucidate the mechanism by which it increased resistance. The loss of DOK2 decreased the level of apoptosis in response to carboplatin. Furthermore, in cells with reduced DOK2, the level of anoikis was decreased. Conclusions. We have developed a screening methodology that analyzes the epigenome and informatically identifies candidate genes followed by in vitro culture screening of the candidate genes. To validate our screening methodology we further characterized one candidate gene, DOK2, and showed that loss of DOK2 induces chemotherapy resistance by decreasing the level of apoptosis in response to treatment. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved

    Subsurface Eddy Facilitates Retention of Simulated Diel Vertical Migrators In a Biological Hotspot

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    Diel vertical migration (DVM) is common in zooplankton populations worldwide. Every day, zooplankton leave the productive surface ocean and migrate to deepwater to avoid visual predators and return to the surface at night to feed. This behavior may also help retain migrating zooplankton in biological hotspots. Compared to fast and variable surface currents, deep ocean currents are sluggish, and can be more consistent. The time spent in the subsurface layer is driven by day length and the depth of the surface mixed layer. A subsurface, recirculating eddy has recently been described in Palmer Deep Canyon (PDC), a submarine canyon in a biological hotspot located adjacent to the West Antarctic Peninsula. Circulation model simulations have shown that residence times of neutrally buoyant particles increase with depth within this feature. We hypothesize that DVM into the subsurface eddy increases local retention of migrating zooplankton in this feature and that shallow mixed layers and longer days increase residence times. We demonstrate that simulated vertically migrating zooplankton can have residence times on the order of 30 days over the canyon, which is five times greater than residence times of near-surface, nonmigrating zooplankton within PDC and other adjacent coastal regions. The potential interaction of zooplankton with this subsurface feature may be important to the establishment of the biological hotspot around PDC by retaining food resources in the region. Acoustic field observations confirm the presence of vertical migrators in this region, suggesting that zooplankton retention due to the subsurface eddy is feasible

    Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis

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    Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections. Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS. Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. Health care professionals were asked to report patients after a minimum of 7 days from initial symptom onset and after sufficient time had passed to observe the COVID-19 disease course through resolution of acute illness or death. Data collection began April 1, 2020, and is ongoing. Exposures: Laboratory-positive SARS-CoV-2 infection or highly suspected COVID-19. Main Outcomes and Measures: Clinical outcome with 4 levels of increasing severity: not hospitalized, hospitalization only, admission to the intensive care unit and/or required ventilator support, and death. Results: Of 1626 patients, most had laboratory-positive SARS-CoV-2 infection (1345 [82.7%]), were female (1202 [74.0%]), and had relapsing-remitting MS (1255 [80.4%]). A total of 996 patients (61.5%) were non-Hispanic White, 337 (20.8%) were Black, and 190 (11.7%) were Hispanic/Latinx. The mean (SD) age was 47.7 (13.2) years, and 797 (49.5%) had 1 or more comorbidity. The overall mortality rate was 3.3% (95% CI, 2.5%-4.3%). Ambulatory disability and older age were each independently associated with increased odds of all clinical severity levels compared with those not hospitalized after adjusting for other risk factors (nonambulatory: hospitalization only, odds ratio [OR], 2.8 [95% CI, 1.6-4.8]; intensive care unit/required ventilator support, OR, 3.5 [95% CI, 1.6-7.8]; death, OR, 25.4 [95% CI, 9.3-69.1]; age [every 10 years]: hospitalization only, OR, 1.3 [95% CI, 1.1-1.6]; intensive care unit/required ventilator support, OR, 1.3 [95% CI, 0.99-1.7]; death, OR, 1.8 [95% CI, 1.2-2.6]). Conclusions and Relevance: In this registry-based cross-sectional study, increased disability was independently associated with worse clinical severity including death from COVID-19. Other risk factors for worse outcomes included older age, Black race, cardiovascular comorbidities, and recent treatment with corticosteroids. Knowledge of these risk factors may improve the treatment of patients with MS and COVID-19 by helping clinicians identify patients requiring more intense monitoring or COVID-19 treatment

    An intermediate-depth source of hydrothermal 3He and dissolved iron in the North Pacific

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    We observed large water column anomalies in helium isotopes and trace metal concentrations above the Loihi Seamount. The 3He/4He of the added helium was 27.3 times the atmospheric ratio, clearly marking its origin to a primitive mantle plume. The dissolved iron to 3He ratio (dFe:3He) exported to surrounding waters was 9.3 ± 0.3 × 106. We observed the Loihi 3He and dFe “signal” at a depth of 1100 m at several stations within ∼100 – 1000 km of Loihi, which exhibited a distal dFe:3He ratio of ∼4 × 106, about half the proximal ratio. These ratios were remarkably similar to those observed over and near the Southern East Pacific Rise (SEPR) despite greatly contrasting geochemical and volcanictectonic origins. In contrast, the proximal and distal dMn:3He ratios were both ∼ 1 × 106, less than half of that observed at the SEPR. Dissolved methane was minimally enriched in waters above Loihi Seamount and was distally absent. Using an idealized regional-scale model we replicated the historically observed regional 3He distribution, requiring a hydrothermal 3He source from Loihi of 10.4 ± 4.2 mola−1, ∼2% of the global abyssal hydrothermal 3He flux. From this we compute a corresponding dFe flux of ∼40 Mmola−1. Global circulation model simulations suggest that the Loihi-influenced waters eventually upwell along the west coast of North America, also extending into the shallow northwest Pacific, making it a possibly important determinant of marine primary production in the subpolar North Pacific
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