123 research outputs found

    Perception of Nuclear Energy and Coal in France and the Netherlands

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    This study focuses on the perception of large scale application of nuclear energy and coal in the Netherlands and France. The application of these energy-sources and the risks and benefits are judged differently by various group in society. In Europe, France has the highest density of nuclear power plants and the Netherlands has one of the lowest. In both countries scientists and social scientists completed a questionnaire assessing the perception of the large scale application of both energy sources. Furthermore, a number of variables relating to the socio cultural and political circumstances were measured. The results indicate that the French had a higher risk perception and a more negative attitude toward nuclear power than the Dutch. But they also assess the benefits of the use of nuclear power to be higher. Explanations for these differences are discussed

    Development of an opportunistic diagnostic prediction algorithm for osteoporosis and fragility fracture risk estimates from forearm radiographs (The OFFER1 Study)

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    This is a preprintData availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.Osteoporosis and associated fractures are an increasingly prevalent concern in context with an ageing population. This study reports testing of IBEX Bone Health (IBEX BH) software, applied following acquisition of forearm radiographs. IBEX BH analyses the radiograph to measure areal bone mineral density (aBMD) at the examination site. A non-randomised cross-sectional study design was performed involving 261 (254 after exclusions) participants (112/142 m/f; mean age 70.8years (SD+/-9.0); 53 with osteoporosis). They underwent posterior-anterior distal forearm radiographs; dual x-ray absorptiometry (DXA) of the wrists, hips and lumbar spine; and, questionnaires exploring clinical risk factors. IBEX BH automatically identifies regions of interest (ROI) at the ultra-distal (UD) and distal third (TD) regions of the radius. Analysis investigated the area under the receiver operating characteristics curve (AUC) performance of IBEX BH for prediction of i) osteoporosis (based on clinical reporting of the hip and spine DXA) and ii) treatment recommendations by Fracture Risk Assessment Tool (FRAX) inclusive of neck of femur (NoF) areal bone mineral density (aBMD) results following National Osteoporosis Guideline Group (NOGG) guidelines. AUC for osteoporosis prediction at the UD and TD ROIs were 0.86 (99% Confidence interval (CI) [0.80, 0.91]) and 0.81 (99% CI [0.75, 0.88]), respectively. AUC for treatment recommendation using FRAX inclusive of NoF aBMD at the UD and TD ROIs were 0.95 (99% CI [0.91, 1.00]) and 0.97 (99% CI [0.93,1.00]), respectively. With a matched sensitivity to FRAX (without NoF aBMD) 0.93 (99% CI [0.78, 0.99]), IBEX BH predicted at the UD and TD ROIs recommended treatment outcomes by NOGG guidelines using FRAX (with NoF aBMD) with specificity 0.89 (99% CI 0.83, 0.94]) and 0.93 (99% CI [0.87, 0.97]), respectively. This is compared with 0.60 (99% CI [0.51, 0.69]) for FRAX (without NoF aBMD). Results demonstrate the potential clinical utility of IBEX BH as an opportunistic screening tool.Ibex Innovation

    A hybrid radiation detector for simultaneous spatial and temporal dosimetry

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    In this feasibility study an organic plastic scintillator is calibrated against ionisation chamber measurements and then embedded in a polymer gel dosimeter to obtain a quasi-4D experimental measurement of a radiation field. This hybrid dosimeter was irradiated with a linear accelerator, with temporal measurements of the dose rate being acquired by the scintillator and spatial measurements acquired with the gel dosimeter. The detectors employed in this work are radiologically equivalent; and we show that neither detector perturbs the intensity of the radiation field of the other. By employing these detectors in concert, spatial and temporal variations in the radiation intensity can now be detected and gel dosimeters can be calibrated for absolute dose from a single irradiation

    Assessment of the multidisciplinary education for a major change in clinical practice; a prospective cohort study

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    Background: New approaches are often introduced to the neonatal intensive care unit (NICU) and other areas of the health service in either a haphazard or cataclysmic fashion. The needs of staff education are often addressed incompletely or too late. Rarely is education assessed after the introduction of a major change. We changed the basis of our NICU respiratory support. We conducted a major educational and support program before this intervention. This study documented and assessed the educational components of this change in our health service provision. Methods: Senior medical and nursing staff attended training abroad and an education program was applied for one year prior to the change. Multidisciplinary educational support for doctors, nurses and allied health was continued after the change. Assessment was by anonymous questionnaire, prior to change, at one and at nine months. Our hypothesis was that dissatisfaction with education would be greatest at one month. Results: Both theory education and practical education aspects of the new approach were rated as good to very good and this did not change with time. Difficulty of applying the technique was rated as ambivalent initially but decreased significantly over 9 months until it was rated easy to very easy (p < 0.001). Over all, the change was rated by staff as beneficial, both at the end of the education period and at nine months, with no decrease at one month. Conclusion: If education and training reaches all staff, with a system of mutual and continued support, even large changes in clinical practice can be achieved without the dissatisfaction with the educational process that is often otherwise seen

    Food Risk/Benefit Communication: A Systematic Review

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    A systematic review relevant to the following research questions was conducted (1) the extent to which different theoretical frameworks have been applied to food risk/benefit communication and (2) the impact such food risk/benefit communication interventions have had on related risk/benefit attitudes and behaviors. Fifty four papers were identified. The analysis revealed that (primarily European or US) research interest has been relatively recent. Certain food issues were of greater interest to researchers than others, perhaps reflecting the occurrence of a crisis, or policy concern. Three broad themes relevant to the development of best practice in risk (benefit) communication were identified: the characteristics of the target population; the contents of the information; and the characteristics of the information sources. Within these themes, independent and dependent variables differed considerably. Overall, acute risk (benefit) communication will require advances in communication process whereas chronic communication needs to identify audience requirements. Both citizen's risk/benefit perceptions and (if relevant) related behaviors need to be taken into account, and recommendations for behavioral change need to be concrete and actionable. The application of theoretical frameworks to the study of risk (benefit) communication was infrequent, and developing predictive models of effective risk (benefit) communication may be contingent on improved theoretical perspectives

    IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry

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    To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats

    Níveis de lisina digestível em raçáes, em que se manteve ou não a relação aminoacídica, para frangos de corte de 1 a 21 dias de idade, mantidos em estresse por calor

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    Dois ensaios foram conduzidos para avaliar os efeitos de níveis de lisina digestível em raçáes em que se manteve ou não a relação aminoacídica sobre o desempenho de frangos de corte machos de 1 a 21 dias de idade, criados em alta temperatura. O delineamento experimental utilizado em ambos os ensaios foi o inteiramente casualizado. As aves, no ensaio 1, foram distribuídas em cinco tratamentos (0,92; 0,98; 1,04; 1,10 e 1,16% de lisina digestível em ração convencional), oito repetiçáes e dez aves por repetição. No ensaio 2, os frangos foram distribuídos em quatro tratamentos (1,04; 1,10; 1,16 e 1,22% de lisina digestível em raçáes mantendo a relação aminoacídica), oito repetiçáes e dez aves por repetição. No ensaio 1, os tratamentos influenciaram quadraticamente o ganho de peso e o consumo de ração, que aumentaram até os níveis de 1,14 e 1,09% de lisina, respectivamente. Embora a conversão alimentar tenha melhorado de forma linear, o modelo LRP foi o que melhor se ajustou aos dados, estimando em 1,097% o nível de lisina a partir do qual ocorreu um platô. Não houve efeito dos tratamentos sobre os pesos absolutos do coração, fígado e intestinos, enquanto o peso absoluto da moela aumentou linearmente. O peso absoluto da carcaça aumentou, enquanto os pesos relativos do coração e do fígado reduziram quadraticamente com os tratamentos. No ensaio 2, os tratamentos influenciaram de forma linear crescente o ganho de peso e a conversão alimentar, enquanto o consumo de ração não variou. Os tratamentos influenciaram linearmente o peso absoluto da carcaça, enquanto os pesos absoluto e relativo das vísceras não variaram. Concluiu-se que frangos de corte machos, de 1 a 21 dias de idade, mantidos em estresse por calor, exigem, no mínimo, 1,14 e 1,22% de lisina digestível em ração convencional e em ração em que se manteve a relação aminoacídica, respectivamente.Two trials were conducted to evaluate the effects of digestible lysine levels in diets maintaining or not the relationship of amino acids, on performance of broilers from 1 to 21 days, kept under heat stress. A completely randomized experimental design was used in both trials. In the trial 1, the broilers were allotted in five treatments (0.92; 0.98; 1.04; 1.10 and 1.16% of lysine in conventional diets), eight replicates and ten broilers per replicate. In the trial 2, the broilers were allotted in four treatments (1.04; 1.10; 1.16 and 1.22% of lysine in diet maintaining the relationship of amino acids), eight replicates and ten broilers per replicate. In the trial 1, the digestible lysine levels influenced quadraticly the weight gain and the feed intake that increased up to 1.14 and 1.09%, respectively. Although feed:gain ratio had changed by linear way, the LRP model adjusted better to the data, estimating in 1.097% the lysine level where occurred a "plateau". There was no effect of treatments on absolute weights of heart, liver and intestines, while the absolute weight of gizzard increased linearly. The absolute weight of carcass increased while the relative weights of heart and liver reduced quadraticly. In the trial 2, the treatments influenced in a crescent linear way the weight gain and the feed:gain ratio while the feed intake was not influenced. The treatments influenced linearly the absolute weight of carcass while the absolute and relative weights of the organs were not influenced. It was concluded that male broilers, in the period from 1 to 21 days of age, kept under heat stress, require at least 1.14 and 1.22% of digestible lysine in conventional diet and in diet maintaining the relationship of amino acid, respectively

    The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule

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    Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% Ξ²-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change

    The SR-BI Partner PDZK1 Facilitates Hepatitis C Virus Entry

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    Entry of hepatitis C virus (HCV) into hepatocytes is a multi-step process that involves a number of different host cell factors. Following initial engagement with glycosaminoglycans and the low-density lipoprotein receptor, it is thought that HCV entry proceeds via interactions with the tetraspanin CD81, scavenger receptor class B type I (SR-BI), and the tight-junction proteins claudin-1 (CLDN1) and occludin (OCLN), culminating in clathrin-dependent endocytosis of HCV particles and their pH-dependent fusion with endosomal membranes. Physiologically, SR-BI is the major receptor for high-density lipoproteins (HDL) in the liver, where its expression is primarily controlled at the post-transcriptional level by its interaction with the scaffold protein PDZK1. However, the importance of interaction with PDZK1 to the involvement of SR-BI in HCV entry is unclear. Here we demonstrate that stable shRNA-knockdown of PDZK1 expression in human hepatoma cells significantly reduces their susceptibility to HCV infection, and that this effect can be reversed by overexpression of full length PDZK1 but not the first PDZ domain of PDZK1 alone. Furthermore, we found that overexpression of a green fluorescent protein chimera of the cytoplasmic carboxy-terminus of SR-BI (amino acids 479–509) in Huh-7 cells resulted in its interaction with PDZK1 and a reduced susceptibility to HCV infection. In contrast a similar chimera lacking the final amino acid of SR-BI (amino acids 479–508) failed to interact with PDZK1 and did not inhibit HCV infection. Taken together these results indicate an indirect involvement of PDZK1 in HCV entry via its ability to interact with SR-BI and enhance its activity as an HCV entry factor

    The CD81 Partner EWI-2wint Inhibits Hepatitis C Virus Entry

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    Two to three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor
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