71 research outputs found

    A Comparison of Actual and Hypothetical Willingness to Pay of Parents and Non-Parents for Protecting Infant Health: The Case of Nitrates in Drinking Water

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    We estimate adults’ willingness to pay (WTP) to reduce health risks to their own or other families’ infants to test for altruism. A conjoint analysis of adults paying for bottled water found marginal WTP for reduction in risk of shock, brain damage, and mortality in the cash treatment of 2,2, 3.70, and 9.43,respectively.Inthehypotheticalmarkettheseamountswere9.43, respectively. In the hypothetical market these amounts were 14, 26,and26, and 66, indicating substantial hypothetical bias, although not unexpected due to the topic of infant health. Statistical tests confirm a high degree of altruism in our WTP results, and altruism held even when real money was involved.altruism, conjoint, drinking water, nitrates, validity, willingness to pay, Agricultural and Food Policy, Consumer/Household Economics, Food Consumption/Nutrition/Food Safety, Health Economics and Policy, Institutional and Behavioral Economics, I10, Q53,

    The reproductive cycle, the embryonic and larval development and the metamorphosis of Heliocidaris erythrogramma, echinoidea.

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    The reproductive cycle and the development of Heliocidaris erythrogramma were investigated. The reproductive cycle was examined by regular, monthly samplings of urchins and routine histological techniques. Histochemical tests were employed to establish the phases of the reproductive cycle. Spawning and artificial fertilization were investigated in the laboratory, and the development of H. erythrogramma was followed from fertilization, through cleavage, blastulation, gastrulation, to development of the larva and metamorphosis into the juvenile urchin. A table of abnormal individuals was compiled, and representatives were sectioned in order to provide a better understanding of the processes involved in normal development

    DNA damage response (DDR) pathway engagement in cisplatin radiosensitization of non-small cell lung cancer

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    Non-small cell lung cancers (NSCLC) are commonly treated with a platinum-based chemotherapy such as cisplatin (CDDP) in combination with ionizing radiation (IR). Although clinical trials have demonstrated that the combination of CDDP and IR appear to be synergistic in terms of therapeutic efficacy, the mechanism of synergism remains largely uncharacterized. We investigated the role of the DNA damage response (DDR) in CDDP radiosensitization using two NSCLC cell lines. Using clonogenic survival assays, we determined that the cooperative cytotoxicity of CDDP and IR treatment is sequence dependent, requiring administration of CDDP prior to IR (CDDP-IR). We identified and interrogated the unique time and agent-dependent activation of the DDR in NSCLC cells treated with cisplatin-IR combination therapy. Compared to treatment with CDDP or IR alone, CDDP-IR combination treatment led to persistence of γH2Ax foci, a marker of DNA double-strand breaks (DSB), for up to 24h after treatment. Interestingly, pharmacologic inhibition of DDR sensor kinases revealed the persistence of γ-H2Ax foci in CDDP-IR treated cells is independent of kinase activation. Taken together, our data suggest that delayed repair of DSBs in NSCLC cells treated with CDDP-IR contributes to CDDP radiosensitization and that alterations of the DDR pathways by inhibition of specific DDR kinases can augment CDDP-IR cytotoxicity by a complementary mechanism

    A smart city-smart bay project - establishing an integrated water monitoring system for decision support in Dublin Bay

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    Environmental and water quality monitoring is key to measuring and understanding the chemical and biological quality of water and for taking reactive remedial action. Over the coming years, monitoring of water bodies will increase within Europe, in order to comply with the requirements of the Water Framework Directive (WFD, Council Directive 2000/60/EC), and globally owing to pressure from climate change. The establishment of high quality long-term monitoring programmes is regarded as essential if the implementation of the WFD is to be effective. However, the traditional spot/grab sampling using conventional sampling and laboratory based techniques can introduce a significant financial burden, and is unlikely to provide a reasonable estimate of the true maximum and/or mean concentration for a particular physico-chemical variable in a water body with marked temporal variability. When persistent fluctuations occur, it is likely only to be detected through continuous measurements, which have the capability of detecting sporadic peaks of concentration. The aim of this work is to demonstrate the potential for continuous monitoring data in decision support as part of a smart city project. The multi-modal data system shows potential for low-cost sensing in complex aquatic environments around the city. Continuous monitoring data from both visual and water quality sensors is collected and data from grab samples collected support the observations of trends in water quality

    From evidence to best practice in the management of fractures of the distal radius in adults: working towards a research agenda

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    BACKGROUND: Fracture of the distal radius is a common clinical problem, particularly in older white women with osteoporosis. We report our work towards evidence-based and patient-centred care for adults with these injuries. METHODS: We developed a systematic programme of research that built on our systematic review of the evidence of effectiveness of treatment interventions for these fractures. We devised schemata showing 'typical' care pathways and identified over 100 patient management questions. These depicted the more important decisions taken when progressing along each care pathway. We compiled a comprehensive document summarising the evidence available for each decision point from our reviews of randomised trials of treatment interventions. Using these documents, we undertook a formal and structured consultation process involving key players, including a patient representative, to obtain their views on the available evidence and to establish a research agenda. The resulting feedback was then processed and interpreted, using systematic methods. RESULTS: Some evidence from 114 randomised trials was available for 31 of the 117 patient management questions. However, there was sufficient evidence to base some conclusions of effectiveness for particular interventions in only five of these. Though only 60% of those approached responded, the responses received from the consultation group were often comprehensive and provided important insights into treatment practice and policy. There was a clear acceptance of the aims of the project and, aside from some suggestions for the more explicit inclusion of secondary prevention and management of complications, of the care pathways scheme. Though some respondents stressed that randomised trials were not always appropriate, there was no direct overall criticism of the evidence document and underlying processes. We were able to identify important core themes that underpin management decisions and research from the feedback of the consultation exercise. CONCLUSIONS: Overall, this project is an important advance towards evidence-based and patient-centred management of adults with distal radial fractures. It exposes the serious deficiency in the available evidence but also provides a template for further action. As well as being a valuable basis for viewing and informing current practice, the insights gained from this project should inform a future research agenda

    Peg-interferon lambda treatment induces robust innate and adaptive immunity in chronic hepatitis B patients

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    IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses in vivo. We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks. In a subgroup of patients, the addition of peg-IFNλ provoked high serum levels of antiviral cytokine IL-18. We also observed the enhancement of natural killer cell polyfunctionality and the recovery of a pan-genotypic HBV-specific CD4+ T cells producing IFN-γ with maintenance of HBV-specific CD8+ T cell antiviral and cytotoxic activities. It was only in these patients that we observed strong virological control with reductions in both viral replication and HBV antigen levels. Here, we show for the first time that in vivo peg-IFNλ displays significant immunostimulatory properties with improvements in the main effectors mediating anti-HBV immunity. Interestingly, the maintenance in HBV-specific CD8+ T cells in the presence of peg-IFNλ is in contrast to previous studies showing that peg-IFNa treatment for CHB results in a detrimental effect on the functionality of this important antiviral T cell compartment

    Impact of the coronavirus infectious disease (COVID-19) pandemic on the provision of inflammatory bowel disease (IBD) antenatal care and outcomes of pregnancies in women with IBD

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    © 2021 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/bmjgast-2021-000603Background The impact of COVID-19 on pregnant Inflammatory Bowel Disease (IBD) patients is currently unknown. Reconfiguration of services during the pandemic may negatively affect medical and obstetric care. We aimed to examine the impacts on IBD antenatal care and pregnancy outcomes. Methods Retrospective data were recorded in consecutive patients attending for IBD antenatal care including outpatient appointments, infusion unit visits and advice line encounters. Results We included 244 pregnant women with IBD, of which 75 (30.7%) were on biologics in whom the treatment was stopped in 29.3% at a median 28 weeks gestation. In addition 9% of patients were on corticosteroids and 21.5% continued on thiopurines. The care provided during 460 patient encounters was not affected by the pandemic in 94.1% but 68.2% were performed via telephone (compared to 3% pre-pandemic practice; p<0.0001). One-hundred-ten women delivered 111 alive babies (mean 38.2 weeks gestation, mean birthweight 3324grams) with 12 (11.0%) giving birth before week 37. Birth occurred by vaginal delivery in 72 (56.4%) and by caesarean section in 48 (43.6%) cases. Thirty three were elective (12 for IBD indications) and 15 emergency caesarean sections. Breast feeding rates were low (38.6%). Amongst 244 pregnant women with IBD 1 suspected COVID-19 infection was recorded. Conclusion IBD antenatal care adjustments during the COVID-19 pandemic have not negatively affected patient care. Despite high levels of immunosuppression only a single COVID-19 infection occurred. Adverse pregnancy outcomes were infrequent

    A novel piggybac transposon inducible expression system identifies a role for akt signalling in primordial germ cell migration

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    In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC) lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development

    Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice

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    Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T H 2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T H 2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck cre IL-4Rα −/lox ) and IL-4Rα-responsive control mice. Global IL-4Rα −/− mice showed, as expected, impaired type 2 immunity to N. brasiliensis . Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T H 2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4 + T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα −/− mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility
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