75 research outputs found

    Investigating five key predictive text entry with combined distance and keystroke modelling

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    This paper investigates text entry on mobile devices using only five-keys. Primarily to support text entry on smaller devices than mobile phones, this method can also be used to maximise screen space on mobile phones. Reported combined Fitt's law and keystroke modelling predicts similar performance with bigram prediction using a five-key keypad as is currently achieved on standard mobile phones using unigram prediction. User studies reported here show similar user performance on five-key pads as found elsewhere for novice nine-key pad users

    Coastal road asset management: Dealing with uncertainty using quantitative erosion monitoring and modelling

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    The A183 is an essential transportation link in the northeast UK that joins coastal areas from South Shields to Sunderland. The route runs through the hinterland of Marsden Bay and concerns have been raised about the proximity of the road to the eroding cliff line. The Shoreline Management Plan (Lane and Guthrie, 2007) sets out the overarching management policy in the area and, based on the analyses of historic map data, uses projected coastal cliff retreat rates of 0.1 – 0.2 m a-1, although more recent investigations have suggested the rates may be nearer 0.04 – 0.1 m a-1. Quantitative data on the true rates and nature of cliff erosion are scarce and asset management decisions typically use the higher rate of 0.2 m a-1 when considering the potential impact on road operations and lifespan in order to account for uncertainty and future sea-level rise; which is additionally used to accelerate the predicted rates of retreat. Consequently, an enhanced high order estimate of cliff erosion rates has restricted the serviceability of the A183 to within 20 – 50 years, and there are three areas (pinch points) of particular concern where the close proximity of the cliff line threatens the safe operation of the road. This approach and the data it uses suggest that significant and potentially costly decisions may soon be required to ensure the viability of this vital transport corridor. Set against the context of assumed high cliff erosion rates, and further predicted increases to this metric, this work presents the results of a re-evaluation of existing map and aerial imagery data that highlights the typically high uncertainty associated with historic map data. The errors often exceed the changes being detected in rock cliffs, producing contradictory results and variability in processing and interpretation that restricts the reliability of the data used in current policy decisions. Using a significance-based analysis, questions are raised about how appropriate it is to reduce a three-dimensional recession process down to a single linear retreat. To provide a more appropriate and accurate assessment of the erosion occurring here we present the results of a monitoring approach of the Marsden Bay site using three-dimensional survey analyses to improve understanding of cliff failures at the site and ultimately to aid policy decisions

    Decoding Complex Erosion Responses for the Mitigation of Coastal Rockfall Hazards Using Repeat Terrestrial LiDAR

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    A key factor limiting our understanding of rock slope behavior and associated geohazards is the interaction between internal and external system controls on the nature, rates, and timing of rockfall activity. We use high-resolution, monthly terrestrial light detection and ranging (LiDAR) surveys over a 2 year monitoring period to quantify rockfall patterns across a 0.6 km-long (15.3 × 103 m2) section of a limestone rock cliff on the northeast coast of England, where uncertainty in rates of change threaten the effective planning and operational management of a key coastal cliff top road. Internal system controls, such as cliff material characteristics and foreshore geometry, dictate rockfall characteristics and background patterns of activity and demonstrate that layer-specific analyses of rockfall inventories and sequencing patterns are essential to better understand the timing and nature of rockfall risks. The influence of external environmental controls, notably storm activity, is also evaluated, and increased storminess corresponds to detectable rises in both total and mean rockfall volume and the volumetric contribution of large (>10 m3) rockfalls at the cliff top during these periods. Transient convergence of the cumulative magnitude–frequency power law scaling exponent (Ι‘) during high magnitude events signals a uniform erosion response across the wider cliff system that applies to all lithologies. The tracking of rockfall distribution metrics from repeat terrestrial LiDAR in this way demonstrably improves the ability to identify, monitor, and forecast short-term variations in rockfall hazards, and, as such, provides a powerful new approach for mitigating the threats and impacts of coastal erosion

    Penetrance of colorectal cancer among MLH1/MSH2 carriers participating in the colorectal cancer familial registry in Ontario

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    <p>Abstract</p> <p>Background</p> <p>Several DNA mismatch repair (MMR) genes, responsible for the majority of Lynch Syndrome cancers, have been identified, predominantly <it>MLH1 </it>and <it>MSH2</it>, but the risk associated with these mutations is still not well established. The aim of this study is to provide population-based estimates of the risks of colorectal cancer (CRC) by gender and mutation type from the Ontario population.</p> <p>Methods</p> <p>We analyzed 32 families segregating MMR mutations selected from the Ontario Familial Colorectal Cancer Registry and including 199 first-degree and 421 second-degree relatives. The cumulative risks were estimated using a modified segregation-based approach, which allows correction for the ascertainment of the Lynch Syndrome families and permits account to be taken for missing genotype information.</p> <p>Results</p> <p>The risks of developing CRC by age 70 were 60% and 47% among men and women carriers of any MMR mutation, respectively. Among <it>MLH1 </it>mutation carriers, males had significantly higher risks than females at all ages (67% vs. 35% by age 70, p-value = 0.02), while the risks were similar in <it>MSH2 </it>carriers (about 54%). The relative risk associated with <it>MLH1 </it>was almost constant with age (hazard ratio (HR) varied between 5.5-5.1 over age 30–70), while the HR for <it>MSH2 </it>decreased with age (from 13.1 at age 30 to 5.4 at age 70).</p> <p>Conclusion</p> <p>This study provides a unique population-based study of CRC risks among <it>MSH2</it>/<it>MLH1 </it>mutation carriers in a Canadian population and can help to better define and understand the patterns of risks among members of Lynch Syndrome families.</p

    The impact of televised tobacco control advertising content on campaign recall: evidence from the International Tobacco Control (ITC) United Kingdom Survey

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    BACKGROUND: Although there is some evidence to support an association between exposure to televised tobacco control campaigns and recall among youth, little research has been conducted among adults. In addition, no previous work has directly compared the impact of different types of emotive campaign content. The present study examined the impact of increased exposure to tobacco control advertising with different types of emotive content on rates and durations of self-reported recall. METHODS: Data on recall of televised campaigns from 1,968 adult smokers residing in England through four waves of the International Tobacco Control (ITC) United Kingdom Survey from 2005 to 2009 were merged with estimates of per capita exposure to government-run televised tobacco control advertising (measured in GRPs, or Gross Rating Points), which were categorised as either β€œpositive” or β€œnegative” according to their emotional content. RESULTS: Increased overall campaign exposure was found to significantly increase probability of recall. For every additional 1,000 GRPs of per capita exposure to negative emotive campaigns in the six months prior to survey, there was a 41% increase in likelihood of recall (OR = 1.41, 95% CI: 1.24–1.61), while positive campaigns had no significant effect. Increased exposure to negative campaigns in both the 1–3 months and 4–6 month periods before survey was positively associated with recall. CONCLUSIONS: Increased per capita exposure to negative emotive campaigns had a greater effect on campaign recall than positive campaigns, and was positively associated with increased recall even when the exposure had occurred more than three months previously

    Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women: the effect of socioeconomic status and antibiotic exposure

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    Objective A growing body of research has investigated the human microbiota and pregnancy outcomes, especially preterm birth. Most studies of the prenatal microbiota have focused on the vagina, with fewer investigating other body sites during pregnancy. Although pregnancy involves profound hormonal, immunological and metabolic changes, few studies have investigated either shifts in microbiota composition across pregnancy at different body sites or variation in composition at any site that may be explained by maternal characteristics. The purpose of this study was to investigate: (1) the stability of the vaginal, oral, and gut microbiota from early (8–14 weeks) through later (24–30 weeks) pregnancy among African American women according to measures of socioeconomic status, accounting for prenatal antibiotic use; (2) whether measures of socioeconomic status are associated with changes in microbiota composition over pregnancy; and (3) whether exposure to prenatal antibiotics mediate any observed associations between measures of socioeconomic status and stability of the vaginal, oral, and gut microbiota across pregnancy. Methods We used paired vaginal, oral, or gut samples available for 16S rRNA gene sequencing from two time points in pregnancy (8–14 and 24–30 weeks) to compare within-woman changes in measures of alpha diversity (Shannon and Chao1) and beta-diversity (Bray–Curtis dissimilarity) among pregnant African American women (nΒ =Β 110). Multivariable linear regression was used to examine the effect of level of education and prenatal health insurance as explanatory variables for changes in diversity, considering antibiotic exposure as a mediator, adjusting for age, obstetrical history, and weeks between sampling. Results For the oral and gut microbiota, there were no significant associations between measures of socioeconomic status or prenatal antibiotic use and change in Shannon or Chao1 diversity. For the vaginal microbiota, low level of education (high school or less) was associated with an increase in Shannon and Chao1 diversity over pregnancy, with minimal attenuation when controlling for prenatal antibiotic use. Conversely, for within-woman Bray–Curtis dissimilarity for early compared to later pregnancy, low level of education and prenatal antibiotics were associated with greater dissimilarity for the oral and gut sites, with minimal attenuation when controlling for prenatal antibiotics, and no difference in dissimilarity for the vaginal site. Conclusions Measures of maternal socioeconomic status are variably associated with changes in diversity across pregnancy for the vaginal, oral, and gut microbiota, with minimal attenuation by prenatal antibiotic exposure. Studies that evaluate stability of the microbiota across pregnancy in association with health outcomes themselves associated with socioeconomic status (such as preterm birth) should incorporate measures of socioeconomic status to avoid finding spurious relationships

    Distinct Roles for Dectin-1 and TLR4 in the Pathogenesis of Aspergillus fumigatus Keratitis

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    Aspergillus species are a major worldwide cause of corneal ulcers, resulting in visual impairment and blindness in immunocompetent individuals. To enhance our understanding of the pathogenesis of Aspergillus keratitis, we developed a murine model in which red fluorescent protein (RFP)-expressing A. fumigatus (Af293.1RFP) conidia are injected into the corneal stroma, and disease progression and fungal survival are tracked over time. Using Mafia mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, we demonstrated that the presence of resident corneal macrophages is essential for production of IL-1Ξ² and CXCL1/KC, and for recruitment of neutrophils and mononuclear cells into the corneal stroma. We found that Ξ²-glucan was highly expressed on germinating conidia and hyphae in the cornea stroma, and that both Dectin-1 and phospho-Syk were up-regulated in infected corneas. Additionally, we show that infected Dectin-1βˆ’/βˆ’ corneas have impaired IL-1Ξ² and CXCL1/KC production, resulting in diminished cellular infiltration and fungal clearance compared with control mice, especially during infection with clinical isolates expressing high Ξ²-glucan. In contrast to Dectin 1βˆ’/βˆ’ mice, cellular infiltration into infected TLR2βˆ’/βˆ’, TLR4βˆ’/βˆ’, and MD-2βˆ’/βˆ’ mice corneas was unimpaired, indicating no role for these receptors in cell recruitment; however, fungal killing was significantly reduced in TLR4βˆ’/βˆ’ mice, but not TLR2βˆ’/βˆ’ or MD-2βˆ’/βˆ’ mice. We also found that TRIFβˆ’/βˆ’ and TIRAPβˆ’/βˆ’ mice exhibited no fungal-killing defects, but that MyD88βˆ’/βˆ’ and IL-1R1βˆ’/βˆ’ mice were unable to regulate fungal growth. In conclusion, these data are consistent with a model in which Ξ²-glucan on A.fumigatus germinating conidia activates Dectin-1 on corneal macrophages to produce IL-1Ξ², and CXCL1, which together with IL-1R1/MyD88-dependent activation, results in recruitment of neutrophils to the corneal stroma and TLR4-dependent fungal killing

    Distinct Roles for Dectin-1 and TLR4 in the Pathogenesis of Aspergillus fumigatus Keratitis

    Get PDF
    Aspergillus species are a major worldwide cause of corneal ulcers, resulting in visual impairment and blindness in immunocompetent individuals. To enhance our understanding of the pathogenesis of Aspergillus keratitis, we developed a murine model in which red fluorescent protein (RFP)-expressing A. fumigatus (Af293.1RFP) conidia are injected into the corneal stroma, and disease progression and fungal survival are tracked over time. Using Mafia mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, we demonstrated that the presence of resident corneal macrophages is essential for production of IL-1Ξ² and CXCL1/KC, and for recruitment of neutrophils and mononuclear cells into the corneal stroma. We found that Ξ²-glucan was highly expressed on germinating conidia and hyphae in the cornea stroma, and that both Dectin-1 and phospho-Syk were up-regulated in infected corneas. Additionally, we show that infected Dectin-1βˆ’/βˆ’ corneas have impaired IL-1Ξ² and CXCL1/KC production, resulting in diminished cellular infiltration and fungal clearance compared with control mice, especially during infection with clinical isolates expressing high Ξ²-glucan. In contrast to Dectin 1βˆ’/βˆ’ mice, cellular infiltration into infected TLR2βˆ’/βˆ’, TLR4βˆ’/βˆ’, and MD-2βˆ’/βˆ’ mice corneas was unimpaired, indicating no role for these receptors in cell recruitment; however, fungal killing was significantly reduced in TLR4βˆ’/βˆ’ mice, but not TLR2βˆ’/βˆ’ or MD-2βˆ’/βˆ’ mice. We also found that TRIFβˆ’/βˆ’ and TIRAPβˆ’/βˆ’ mice exhibited no fungal-killing defects, but that MyD88βˆ’/βˆ’ and IL-1R1βˆ’/βˆ’ mice were unable to regulate fungal growth. In conclusion, these data are consistent with a model in which Ξ²-glucan on A.fumigatus germinating conidia activates Dectin-1 on corneal macrophages to produce IL-1Ξ², and CXCL1, which together with IL-1R1/MyD88-dependent activation, results in recruitment of neutrophils to the corneal stroma and TLR4-dependent fungal killing
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