1,150 research outputs found

    Potential for HPV vaccination and primary HPV screening to reduce cervical cancer disparities: Example from New Zealand

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    Background Cervical cancer rates are over twice as high, and screening coverage is lower, in Māori women compared to other women in New Zealand, whereas uptake of HPV vaccine is higher in Maori females. We aimed to assess the impact of HPV vaccination and the proposed transition to 5-yearly primary HPV screening in Māori and other women in New Zealand, at current participation levels; and additionally to investigate which improvements to participation in Māori females (in vaccination, screening, or surveillance for screening-defined higher-risk women) would have the greatest impact on cervical cancer incidence/mortality. Methods An established model of HPV vaccination and cervical screening in New Zealand was adapted to fit observed ethnicity-specific data. Ethnicity-specific models were used to estimate the long-term impact of vaccination and screening (vaccination coverage 63% vs 47%; five-year screening coverage 68% vs 81% in Maori vs European/Other women, respectively). Results Shifting from cytology to HPV-based screening is predicted to reduce cervical cancer incidence by 17% (14%) in Maori (European/Other) women, respectively. The corresponding reductions due to vaccination and HPV-based screening combined were 58% (44%), but at current participation levels long-term incidence would remain almost twice as high in Māori women (6.1/100,000 compared to 3.1/100,00 in European/Other women). Among strategies we examined, the greatest impact came from high vaccine coverage and achieving higher attendance by Māori women under surveillance for screen-detected abnormalities. Conclusion Relative reductions in cervical cancer due to vaccination and HPV-based screening are predicted to be greater in Maori than in European/Other women. While these interventions have the potential to substantially reduce between-group differences, cervical cancer incidence would remain higher in Maori women. These findings highlight the importance of multiple approaches and the potential influence of factors beyond HPV prevention

    A revision of sexual mixing matrices in models of sexually transmitted infection

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    Two sexual mixing matrices previously used in models of sexually transmitted infections (STIs) are intended to calculate the probability of sexual interaction between age groups and sexual behaviour subgroups. When these matrices are used to specify multiple criteria for how people select sexual partners (such as age group and sexual behaviour class), their conditional probability structure means that they have in practice been prone to misuse. We constructed revised mixing matrices that incorporate a corrected conditional probability structure and then used one of them to examine the effect of this revision on population modelling of STIs. Using a dynamic model of human papillomavirus (HPV) transmission as an example, we examined changes to estimates of HPV prevalence and the relative reduction in age-standardised HPV incidence after the commencement of publicly funded HPV vaccination in Australia. When all other model specifications were left unchanged, the revised mixing matrix initially led to estimates of age-specific oncogenic HPV prevalence that were up to 11% higher than our previous models at certain ages. After re-calibrating the model by modifying unobservable parameters characterising HPV natural history, the revised mixing matrix yielded similar estimates to our previous models, predicting that vaccination would lead to relative HPV incidence reductions of 43% and 85% by 2010 and 2050, respectively, compared with 43% and 86% using the unrevised mixing matrix formulation. Our revised mixing matrix offers a rigorous alternative to commonly used mixing matrices, which can be used to reliably and explicitly accommodate conditional probabilities, with appropriate re-calibration of unobservable model parameter

    A MAP Kinase Dependent Feedback Mechanism Controls Rho1 GTPase and Actin Distribution in Yeast

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    In the yeast Saccharomyces cerevisiae the guanosine triphosphatase (GTPase) Rho1 controls actin polarization and cell wall expansion. When cells are exposed to various environmental stresses that perturb the cell wall, Rho1 activates Pkc1, a mammalian Protein Kinase C homologue, and Mpk1, a mitogen activated protein kinase (MAPK), resulting in actin depolarization and cell wall remodeling. In this study, we demonstrate a novel feedback loop in this Rho1-mediated Pkc1-MAPK pathway that involves regulation of Rom2, the guanine nucleotide exchange factor of Rho1, by Mpk1, the end kinase of the pathway. This previously unrecognized Mpk1-depedent feedback is a critical step in regulating Rho1 function. Activation of this feedback mechanism is responsible for redistribution of Rom2 and cell wall synthesis activity from the bud to cell periphery under stress conditions. It is also required for terminating Rho1 activity toward the Pkc1-MAPK pathway and for repolarizing actin cytoskeleton and restoring growth after the stressed cells become adapted

    Video summarisation: A conceptual framework and survey of the state of the art

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    This is the post-print (final draft post-refereeing) version of the article. Copyright @ 2007 Elsevier Inc.Video summaries provide condensed and succinct representations of the content of a video stream through a combination of still images, video segments, graphical representations and textual descriptors. This paper presents a conceptual framework for video summarisation derived from the research literature and used as a means for surveying the research literature. The framework distinguishes between video summarisation techniques (the methods used to process content from a source video stream to achieve a summarisation of that stream) and video summaries (outputs of video summarisation techniques). Video summarisation techniques are considered within three broad categories: internal (analyse information sourced directly from the video stream), external (analyse information not sourced directly from the video stream) and hybrid (analyse a combination of internal and external information). Video summaries are considered as a function of the type of content they are derived from (object, event, perception or feature based) and the functionality offered to the user for their consumption (interactive or static, personalised or generic). It is argued that video summarisation would benefit from greater incorporation of external information, particularly user based information that is unobtrusively sourced, in order to overcome longstanding challenges such as the semantic gap and providing video summaries that have greater relevance to individual users

    FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells.

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    BACKGROUND: During its intraerythrocytic asexual reproduction cycle Plasmodium falciparum consumes up to 80% of the host cell hemoglobin, in large excess over its metabolic needs. A model of the homeostasis of falciparum-infected red blood cells suggested an explanation based on the need to reduce the colloid-osmotic pressure within the host cell to prevent its premature lysis. Critical for this hypothesis was that the hemoglobin concentration within the host cell be progressively reduced from the trophozoite stage onwards. METHODOLOGY/PRINCIPAL FINDINGS: The experiments reported here were designed to test this hypothesis by direct measurements of the hemoglobin concentration in live, infected red cells. We developed a novel, non-invasive method to quantify the hemoglobin concentration in single cells, based on Förster resonance energy transfer between hemoglobin molecules and the fluorophore calcein. Fluorescence lifetime imaging allowed the quantitative mapping of the hemoglobin concentration within the cells. The average fluorescence lifetimes of uninfected cohorts was 270+/-30 ps (mean+/-SD; N = 45). In the cytoplasm of infected cells the fluorescence lifetime of calcein ranged from 290+/-20 ps for cells with ring stage parasites to 590+/-13 ps and 1050+/-60 ps for cells with young trophozoites and late stage trophozoite/early schizonts, respectively. This was equivalent to reductions in hemoglobin concentration spanning the range from 7.3 to 2.3 mM, in line with the model predictions. An unexpected ancillary finding was the existence of a microdomain under the host cell membrane with reduced calcein quenching by hemoglobin in cells with mature trophozoite stage parasites. CONCLUSIONS/SIGNIFICANCE: The results support the predictions of the colloid-osmotic hypothesis and provide a better understanding of the homeostasis of malaria-infected red cells. In addition, they revealed the existence of a distinct peripheral microdomain in the host cell with limited access to hemoglobin molecules indicating the concentration of substantial amounts of parasite-exported material

    Out of the empirical box: A mixed-methods study of tool innovation among Congolese BaYaka forager and Bondongo fisher–farmer children

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    © 2021 The Authors. Tool innovation has played a crucial role in human adaptation. Yet, this capacity seems to arise late in development. Before 8 years of age, many children struggle to solve the hook task, a common measure of tool innovation that requires modification of a straight pipe cleaner into a hook to extract a prize. Whether these findings are generalizable beyond postindustrialized Western children remains unclear. In many small-scale subsistence societies, children engage in daily tool use and modification, experiences that theoretically could enhance innovative capabilities. Although two previous studies found no differences in innovative ability between children from Western and small-scale subsistence societies, these did not account for the latter’s inexperience with pipe cleaners. Thus, the current study investigated how familiarity with pipe cleaners affected hook task success in 132 Congolese BaYaka foragers (57 girls) and 59 Bondongo fisher–farmers (23 girls) aged 4–12 years. We contextualized these findings within children’s interview responses and naturalistic observations of how pipe cleaners were incorporated into daily activities. Counter to our expectation, prior exposure did not improve children’s performance during the hook task. Bondongo children innovated significantly more hooks than BaYaka children, possibly because they participate in hook-and-line fishing. Observations and interviews showed that children imagined and innovated novel uses for pipe cleaners outside the experimental context, including headbands, bracelets, and suspenders. We relate our findings to ongoing debates regarding systematic versus unsystematic tool innovation, the importance of prior experience for the ontogeny of tool innovation, and the external validity of experimental paradigms
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