Community readiness and momentum: identifying and including community-driven variables in a mixed-method rural palliative care service siting model.

BACKGROUND: Health service administrators make decisions regarding how to best use limited resources to have the most significant impact. Service siting models are tools that can help in this capacity. Here we build on our own mixed-method service siting model focused on identifying rural Canadian communities most in need of and ready for palliative care service enhancement through incorporating new community-driven insights. METHODS: We conducted 40 semi-structured interviews with formal and informal palliative care providers from four purposefully selected rural communities across Canada. Communities were selected by running our siting model, which incorporated GIS methods, and then identifying locations suitable as qualitative case studies. Participants were identified using multiple recruitment methods. Interviews were transcribed verbatim and the transcripts were reviewed to identify emerging themes and were coded accordingly. Thematic analysis then ensued. RESULTS: We previously introduced the inclusion of a 'community readiness' arm in the siting model. This arm is based on five community-driven indicators of palliative care service enhancement readiness and need. The findings from the current analysis underscore the importance of this arm of the model. However, the data also revealed the need to subjectively assess the presence or absence of community awareness and momentum indicators. The interviews point to factors such as educational tools, volunteers, and local acknowledgement of palliative care priorities as reflecting the presence of community awareness and factors such as new employment and volunteer positions, new care spaces, and new projects and programs as reflecting momentum. The diversity of factors found to illustrate these indicators between our pilot study and current national study demonstrate the need for those using our service siting model to look for contextually-relevant signs of their presence. CONCLUSION: Although the science behind siting model development is established, few researchers have developed such models in an open way (e.g., documenting every stage of model development, engaging with community members). This mixed-method study has addressed this notable knowledge gap. While we have focused on rural palliative care in Canada, the process by which we have developed and refined our siting model is transferrable and can be applied to address other siting problems.

Using a Few Snapshots to Distinguish Mountains from Waves: Weak Factorial Invariance in the Context of Trait-State Research.

In this article, we show that the underlying dimensions obtained when factor analyzing cross-sectional data actually form a mix of within-person state dimensions and between-person trait dimensions. We propose a factor analytical model that distinguishes between four independent sources of variance: common trait, unique trait, common state, and unique state. We show that by testing whether there is weak factorial invariance across the trait and state factor structures, we can tackle the fundamental question first raised by Cattell; that is, are within-person state dimensions qualitatively the same as between-person trait dimensions? Furthermore, we discuss how this model is related to other trait-state factor models, and we illustrate its use with two empirical data sets. We end by discussing the implications for cross-sectional factor analysis and suggest potential future developments.

A Comparison of Inverse-Wishart Prior Specifications for Covariance Matrices in Multilevel Autoregressive Models.

Multilevel autoregressive models are especially suited for modeling between-person differences in within-person processes. Fitting these models with Bayesian techniques requires the specification of prior distributions for all parameters. Often it is desirable to specify prior distributions that have negligible effects on the resulting parameter estimates. However, the conjugate prior distribution for covariance matrices-the Inverse-Wishart distribution-tends to be informative when variances are close to zero. This is problematic for multilevel autoregressive models, because autoregressive parameters are usually small for each individual, so that the variance of these parameters will be small. We performed a simulation study to compare the performance of three Inverse-Wishart prior specifications suggested in the literature, when one or more variances for the random effects in the multilevel autoregressive model are small. Our results show that the prior specification that uses plug-in ML estimates of the variances performs best. We advise to always include a sensitivity analysis for the prior specification for covariance matrices of random parameters, especially in autoregressive models, and to include a data-based prior specification in this analysis. We illustrate such an analysis by means of an empirical application on repeated measures data on worrying and positive affect.

Specific serology for emerging human coronaviruses by protein microarray.

We present a serological assay for the specific detection of IgM and IgG antibodies against the emerging human coronavirus hCoV-EMC and the SARS-CoV based on protein microarray technology. The assay uses the S1 receptor-binding subunit of the spike protein of hCoV-EMC and SARS-CoV as antigens. The assay has been validated extensively using putative cross-reacting sera of patient cohorts exposed to the four common hCoVs and sera from convalescent patients infected with hCoV-EMC or SARS-CoV.

A proposed methodology to estimate the cumulative life-time UVB exposure using geographic information systems: An application to multiple sclerosis.

BACKGROUND: The cause of multiple sclerosis (MS) is unknown; multiple risk factors have been implicated, including environmental exposures, such as sunlight. Many studies have relied on latitude alone as a crude proxy for sunlight exposure. We aimed to develop a protocol allowing a more detailed estimate of cumulative ambient ultra-violet B (UVB) exposure at critical time-periods over a patient's life-course. METHODS: 4010 definite MS patients with a 'movement history' from birth to the study end (2005) were selected from the University of British Columbia, Canada's MS Genetic database. Patient's place of resident from birth were tracked, each place being geocoded (latitude and longitude) and assigned a UVB value using the NASA Total Ozone Mapping Spectrometer (TOMS) dataset. Combined, these data allowed an estimated UVB value for each patient based on year and location. RESULTS: Using this protocol, we provide a potentially more detailed cumulative UVB exposure for critical periods in a patients' life history based on their individual spatial migration through time. CONCLUSIONS: This protocol is intended to provide a framework for researchers to more accurately estimate UVB exposures for individuals over the course of their life history and may be useful for understanding etiology of MS and other chronic disease.

Are injuries spatially related? Join-count spatial autocorrelation for small-area injury analysis.

OBJECTIVE: To present a geographic information systems (GIS) method for exploring the spatial pattern of injuries and to demonstrate the utility of using this method in conjunction with classic ecological models of injury patterns. DESIGN: Profiles of patients' socioeconomic status (SES) were constructed by linking their postal code of residence to the census dissemination area that encompassed its location. Data were then integrated into a GIS, enabling the analysis of neighborhood contiguity and SES on incidence of injury. SETTING: Data for this analysis (2001-2006) were obtained from the British Columbia Trauma Registry. Neighborhood SES was calculated using the Vancouver Area Neighborhood Deprivation Index. Spatial analysis was conducted using a join-count spatial autocorrelation algorithm. PATIENTS: Male and female patients over the age of 18 and hospitalized from severe injury (Injury Severity Score >12) resulting from an assault or intentional self-harm and included in the British Columbia Trauma Registry were analyzed. RESULTS: Male patients injured by assault and who resided in adjoining census areas were observed 1.3 to 5 times more often than would be expected under a random spatial pattern. Adjoining neighborhood clustering was less visible for residential patterns of patients hospitalized with injuries sustained from self-harm. A social gradient in assault injury rates existed separately for men and neighborhood SES, but less than would be expected when stratified by age, gender, and neighborhood. No social gradient between intentional injury from self-harm and neighborhood SES was observed. CONCLUSIONS: This study demonstrates the added utility of integrating GIS technology into injury prevention research. Crucial information on the associated social and environmental influences of intentional injury patterns may be under-recognized if a spatial analysis is not also conducted. The join-count spatial autocorrelation is an ideal approach for investigating the interconnectedness of injury patterns that are rare and occur in only a small percentage of the population.

The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins.

OBJECTIVES: Many enveloped viruses carry carbohydrate-containing proteins on their surface. These glycoproteins are key to the infection process as they are mediators of the receptor binding and membrane fusion of the virion with the host cell. Therefore, they are attractive therapeutic targets for the development of novel antiviral therapies. Recently, carbohydrate-binding agents (CBA) were shown to possess antiviral activity towards coronaviruses. The current study further elucidates the inhibitory mode of action of CBA. METHODS: Different strains of two coronaviruses, mouse hepatitis virus and feline infectious peritonitis virus, were exposed to CBA: the plant lectins Galanthus nivalis agglutinin, Hippeastrum hybrid agglutinin and Urtica dioica agglutinin (UDA) and the non-peptidic mannose-binding antibiotic pradimicin A. RESULTS AND CONCLUSIONS: Our results indicate that CBA target the two glycosylated envelope glycoproteins, the spike (S) and membrane (M) protein, of mouse hepatitis virus and feline infectious peritonitis virus. Furthermore, CBA did not inhibit virus-cell attachment, but rather affected virus entry at a post-binding stage. The sensitivity of coronaviruses towards CBA was shown to be dependent on the processing of the N-linked carbohydrates. Inhibition of mannosidases in host cells rendered the progeny viruses more sensitive to the mannose-binding agents and even to the N-acetylglucosamine-binding UDA. In addition, inhibition of coronaviruses was shown to be dependent on the cell-type used to grow the virus stocks. All together, these results show that CBA exhibit promising capabilities to inhibit coronavirus infections.

Comparative evaluation of the activity of antivirals towards feline immunodeficiency virus in different cell culture systems.

Influences of the cell system on observed EC(50) values of different agents against feline immunodeficiency virus (FIV) were assessed. The activity of various nucleoside reverse transcriptase inhibitors (NRTI) against a lymphotropic FIV strain was evaluated using monocultured thymocytes and a DC-thymocyte coculture. In the second set of experiments activity of carbohydrate binding agents (CBA) towards FIV strains derived from different cell lines (e.g. Crandall feline kidney cells (CRFK) and thymocytes) was compared. We examined three different FIV-based antiviral evaluation systems and obtained marked differences in EC(50) values, especially for CBA entry inhibitors. Our study confirms and extends earlier observed differences between cell systems used for the evaluation of the activity of antivirals towards FIV.

Antiviral activity of carbohydrate-binding agents against Nidovirales in cell culture.

Coronaviruses are important human and animal pathogens, the relevance of which increased due to the emergence of new human coronaviruses like SARS-CoV, HKU1 and NL63. Together with toroviruses, arteriviruses, and roniviruses the coronaviruses belong to the order Nidovirales. So far antivirals are hardly available to combat infections with viruses of this order. Therefore, various antiviral strategies to counter nidoviral infections are under evaluation. Lectins, which bind to N-linked oligosaccharide elements of enveloped viruses, can be considered as a conceptionally new class of virus inhibitors. These agents were recently evaluated for their antiviral activity towards a variety of enveloped viruses and were shown in most cases to inhibit virus infection at low concentrations. However, limited knowledge is available for their efficacy towards nidoviruses. In this article the application of the plant lectins Hippeastrum hybrid agglutinin (HHA), Galanthus nivalis agglutinin (GNA), Cymbidium sp. agglutinin (CA) and Urtica dioica agglutinin (UDA) as well as non-plant derived pradimicin-A (PRM-A) and cyanovirin-N (CV-N) as potential antiviral agents was evaluated. Three antiviral tests were compared based on different evaluation principles: cell viability (MTT-based colorimetric assay), number of infected cells (immunoperoxidase assay) and amount of viral protein expression (luciferase-based assay). The presence of carbohydrate-binding agents strongly inhibited coronaviruses (transmissible gastroenteritis virus, infectious bronchitis virus, feline coronaviruses serotypes I and II, mouse hepatitis virus), arteriviruses (equine arteritis virus and porcine respiratory and reproductive syndrome virus) and torovirus (equine Berne virus). Remarkably, serotype II feline coronaviruses and arteriviruses were not inhibited by PRM-A, in contrast to the other viruses tested.

Feline immunodeficiency virus infection is enhanced by feline bone marrow-derived dendritic cells.

In the pathogenesis of feline immunodeficiency virus (FIV) infection, feline dendritic cells (feDCs) are thought to play an important role. As with DCs in other species, feDCs are believed to transport virus particles to lymph nodes and transfer them to lymphocytes. Our investigation has focused on the ability of feDCs to influence the infection of syngeneic peripheral blood mononuclear cells (PBMCs) and allogeneic thymocytes. feDCs were derived from bone marrow mononuclear cells that were cultured under the influence of feline interleukin-4 and feline granulocyte-macrophage colony-stimulating factor. By using these feDCs in co-culture with resting PBMCs, an upregulation of FIV replication was shown. An enhancement of FIV infection was also detected when co-cultures of feDCs/feline thymocytes were infected. To obtain this enhancement, direct contact of the cells in the co-culture was necessary; transwell cultures showed that the involvement of only soluble factors produced by feDCs in this process is not likely. These feDCs were also able to induce the proliferation of resting thymocytes, which might explain the enhanced FIV replication observed. Together, these data suggest that feDCs have abilities similar to those shown for simian and human DCs in the interaction with leukocytes. This system is suitable for further investigations of the interplay of DC and T cells during FIV infection in vitro.

A single amino acid substitution in the transmembrane envelope glycoprotein of feline immunodeficiency virus alters cellular tropism.

The cellular tropism of the feline immunodeficiency virus (FIV) is affected by changes in variable region 3 (V3) of the surface (SU) envelope glycoprotein (Verschoor, E. J., et al., J. Virol. 69:4752-4757, 1995). By using high-dose DNA transfection, an FIV molecular clone with a non-CRFK-tropic V3 acquired the ability to replicate in CRFK cells. A single point mutation from a methionine to a threonine in the ectodomain of its transmembrane (TM) envelope glycoprotein was responsible for this change in viral tropism. This substitution is located in the putative SU interactive region, between the fusion peptide and the membrane-spanning region. Our results show that this region of the TM envelope glycoprotein constitutes an additional determinant for cell tropism.

Monoclonal antibodies to immunodominant and neutralizing domains of the envelope surface protein of feline immunodeficiency virus.

Hybridomas secreting monoclonal antibodies (MAbs) specific for the surface protein (SU) of feline immunodeficiency virus were generated. Four MAbs were obtained which could be assigned to two groups based on their neutralization and competition behaviour. Using SU protein fragments expressed in Escherichia coli the antigenic site recognized by one of the MAbs (2H11) could be mapped to the c terminus. The neutralizing MAb 1E1 did not bind to any of the SU protein fragments and was directed to a conformational epitope. Binding of the MAb 1E1 to native SU protein could be blocked with a rabbit serum raised against the SU3 fragment (amino acids 361 to 445). These data indicate that at least part of the epitope is located on this SU3 domain. In competition experiments most sera of naturally infected cats were able to inhibit binding of the MAbs. This shows the conserved and immunodominant nature of the epitopes involved.