183 research outputs found

    A Monolayer of Primary Colonic Epithelium Generated on a Scaffold with a Gradient of Stiffness for Drug Transport Studies

    Get PDF
    Animal models are frequently used for in vitro physiologic and drug transport studies of the colon, but there exists significant pressure to improve assay throughput as well as to achieve tighter control of experimental variables than can be achieved with animals. Thus, development of a primary in vitro colonic epithelium cultured as high resistance with transport protein expression and functional behavior similar to that of a native colonic would be of enormous value for pharmaceutical research. A collagen scaffold, in which the degree of collagen cross-linking was present as a gradient, was developed to support the proliferation of primary colonic cells. The gradient of cross-linking created a gradient in stiffness across the scaffold, enabling the scaffold to resist deformation by cells. mRNA expression and quantitative proteomic mass spectrometry of cells growing on these surfaces as a monolayer suggested that the transporters present were similar to those in vivo. Confluent monolayers acted as a barrier to small molecules so that drug transport studies were readily performed. Transport function was evaluated using atenolol (a substrate for passive paracellular transport), propranolol (a substrate for passive transcellular transport), rhodamine 123 (Rh123, a substrate for P-glycoprotein), and riboflavin (a substrate for solute carrier transporters). Atenolol was poorly transported with an apparent permeability (Papp) of < 5 × 10-7 cm s-1, while propranolol demonstrated a Papp of 9.69 × 10-6 cm s-1. Rh123 was transported in a luminal direction (Papp,efflux/Papp,influx = 7) and was blocked by verapamil, a known inhibitor of P-glycoprotein. Riboflavin was transported in a basal direction, and saturation of the transporter was observed at high riboflavin concentrations as occurs in vivo. It is anticipated that this platform of primary colonic epithelium will find utility in drug development and physiological studies, since the tissue possesses high integrity and active transporters and metabolism similar to that in vivo

    Poultry Drinking Water Used for Avian Influenza Surveillance

    Get PDF
    Samples of drinking water from poultry cages, which can be collected conveniently and noninvasively, provide higher rates of influenza (H9N2) virus isolation than do samples of fecal droppings. Studies to confirm the usefulness of poultry drinking water for detecting influenza (H5N1) should be conducted in disease-endemic areas

    Production and Clinical Evaluation of Norwalk GI.1 Virus Lot 001-09NV in Norovirus Vaccine Development

    Get PDF
    Background: Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains are needed to assess vaccine efficacy in the controlled human infection model (CHIM). Methods: A stock of HuNoV strain Norwalk virus ([NV] GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses. Results: Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells. Conclusions: GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates

    Using job strain and organizational justice models to predict multiple forms of employee performance behaviours among Australian policing personnel

    Full text link
    The overall purpose of this investigation was to examine the relationship between stress-related working conditions and three forms of employee performance behaviours: in-role behaviours, citizenship behaviours directed at other individuals and citizenship behaviours directed at the organization. The potentially stressful working conditions were based on the job strain model (incorporating job demands, job control and social support) as well as organizational justice theory. A sample of Australian-based police officers (n = 640) took part in this study and the data were collected via a mail-out survey. Multiple regression analyses were undertaken to assess both the strength and the nature of the relationships between the working conditions and employee performance and these analyses included tests for additive, interactional and curvilinear effects. The overall results indicated that a significant proportion of the explained variance in all three outcome measures was attributed to the additive effects of demand, control and support. The level of variance associated with the organizational justice dimensions was relatively small, although there were signs that specific dimensions of justice may provide unique insights into the relationship between job stressors and employee performance. The implications of these and other notable findings are discussed.<br /

    Predicting risk among non-respondents in prospective studies

    Full text link
    Potential non-response bias was investigated in a follow-up study of 2,011 chronically disabled patients. 82.5% and 73.3% of the study subjects responded to self-administered mail questionnaires respectively at 6-month and 1-year follow-up. Information on employment status, the outcome of interest, of approximately 90% of the non-respondents was obtained from indirect sources. Employment rate was lower among the non-respondents than the respondents. Non-response was associated with age, social class, previous employment record, and the type of disability; but none of these characteristics were associated with the outcome. Out of the five known independent risk factors for unemployment, only one (incompletion of rehabilitation course) was associated with non-response. The employment rate among the respondents was also assessed according to the delay in response, that is the number of reminders sent to achieve response. The outcome among- the late respondents was similar to that among the nonrespondents. These data suggest that (a) risk estimates may be biased even when the response rate is greater than 80%, (b) the prevalence of risk factors among non-respondents may not indicate the presence or the degree of non-response bias, but (c) reliable estimates can be obtained from extrapolations of the rates among the respondents according to the delay in response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42663/1/10654_2004_Article_BF00152716.pd

    I will not go, I cannot go: cultural and social limitations of disaster preparedness in Asia, Africa, and Oceania

    Get PDF
    While much work has been invested in addressing the economic and technical basis of disaster preparedness, less effort has been directed towards understanding the cultural and social obstacles to and opportunities for disaster risk reduction. This paper presents local insights from five different national settings into the cultural and social contexts of disaster preparedness. In most cases, an early warning system was in place, but it failed to alert people to diverse environmental shocks. The research findings show that despite geographical and typological differences in these locations, the limitations of the systems were fairly similar. In Kenya, people received warnings, but from contradictory systems, whereas in the Philippines and on the island of Saipan, people did not understand the messages or take them seriously. In Bangladesh and Nepal, however, a deeper cultural and religious reasoning serves to explain disasters, and how to prevent them or find safety when they strike

    Potential for comparative public opinion research in public administration

    Get PDF
    The public administration and public services have always taken a marginal place in the political scientists’ behavioural research. Public administration students on the other hand tend to focus on political and administrative elites and institutions, and largely ignored citizens in comparative research. In this article we make a plea for international comparative research on citizens’ attitudes towards the public administration from an interdisciplinary perspective. Available international survey material is discussed, and main trends in empirical practice and theoretical approaches are outlined, especially those with a potential impact on public sector reform
    corecore