At the grassroots of home and community-based aged care : strategies for successful consumer engagement

Objectives (1) To describe the processes used to plan and conduct a stakeholder forum in aged care as a means of informing future uptake of consumer participatory research. (2) To discuss how capturing and drawing on stakeholders' experiences of aged care can generate new research ideas and inform the delivery of more person-centred aged care services. Key principles of consumer engagement A stakeholder forum was conducted as part of Ageing Well, a 2-year project evaluating the value and impact of social participation and quality of life tools as part of routine community aged care assessments at a large Australian provider. The forum was codesigned with community aged care clients and care coordinators and aimed to coproduce implementation strategies with a targeted representation of stakeholders. The stakeholder forum was developed using five key principles of consumer engagement activities: purposeful, inclusive, timely, transparent and respectful. The forum fostered an environment of mutual respect and collective inquiry to encourage contributions from all participants. This article outlines practical guidance on using a consumer engagement framework and the lessons learnt. Discussion The stakeholder forum facilitated an understanding of consumers' needs and existing gaps in aged care services and the circumstances that can enable or hinder the delivery and implementation of these services. This collective information can guide future research and policy at institutional, regional and national committees that relate to aged care

Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis

INTRODUCTION: Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF)--a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins--many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in an in vivo model of arthritis. METHODS: To identify novel splice variants, we performed RT-PCR using an mRNA pool representing major human tissue types and tumors. Novel ASV were identified by alignment of each cloned sequence to its respective genomic sequence in comparison with full-length transcripts. To test whether these ASV have biologic activity, we characterized a subset of them for ligand binding, and for efficacy in an animal model of arthritis. The in vivo study was accomplished using adenoviruses expressing secreted ASV. RESULTS: We cloned 60 novel human ASV from 21 genes, encoding cell surface receptors--many of which are known to be important in the regulation of angiogenesis. The ASV were characterized by exon extension, intron retention and alternative exon utilization. Efficient expression and secretion of selected ASV--corresponding to VEGF receptor type 1, VEGF receptor type 2, VEGF receptor type 3, angiopoietin receptor Tie1, Met (receptor for hepatocyte growth factor), colony-stimulating factor 1 receptor, platelet-derived growth factor receptor beta, fibroblast growth factor receptor 1, Kit, and RAGE--was demonstrated, together with binding to their cognate ligands. Importantly, ASV derived from VEGF receptor type 1 and Tie1, and to a lesser extent from VEGF receptor type 2 and fibroblast growth factor receptor 1, reduced clinical signs of arthritis in vivo. The reduction was paralleled by decreased joint inflammation and destruction. CONCLUSION: The present study shows that unique ASV derived from receptors that play key roles in angiogenesis--namely, VEGF receptor type 1 and, for the first time, Tie1--can markedly reduce arthritis severity. More broadly, our results demonstrate that ASV are a source of novel proteins with therapeutic potential in diseases in which angiogenesis and cellular hyperplasia play a central role, such as rheumatoid arthritis

The Temperature Scale of Metal-Rich M Giants Based on TiO Bands: Population Synthesis in the Near Infrared

We have computed a grid of high resolution synthetic spectra for cool stars (2500<Teff<6000 K) in the wavelength range 6000 -- 10200A, by employing an updated line list of atomic and molecular lines, together with state-of-the-art model atmospheres. As a by-product, by fitting TiO bandheads in spectra of well-known M giants, we have derived the electronic oscillator strengths of the TiO gamma prime, delta, epsilon and phi systems. The derived oscillator strenghts for the gamma prime, epsilon and phi systems differ from the laboratory and ab initio values found in the literature, but are consistent with the model atmospheres and line lists employed, resulting in a good match to the observed spectra of M giants of known parameters. The behavior of TiO bands as a function of the stellar parameters Teff, log g and [Fe/H] is presented and the use of TiO spectral indices in stellar population studies is discussed.Comment: ApJ accepted, 27 pages + 11 figures, AASLatex v4.

Synthetic Spectra and Color-Temperature Relations of M Giants

As part of a project to model the integrated spectra and colors of elliptical galaxies through evolutionary synthesis, we have refined our synthetic spectrum calculations of M giants. After critically assessing three effective temperature scales for M giants, we adopted the relation of Dyck et al. (1996) for our models. Using empirical spectra of field M giants as a guide, we then calculated MARCS stellar atmosphere models and SSG synthetic spectra of these cool stars, adjusting the band absorption oscillator strengths of the TiO bands to better reproduce the observational data. The resulting synthetic spectra are found to be in very good agreement with the K-band spectra of stars of the appropriate spectral type taken from Kleinmann & Hall (1986) as well. Spectral types estimated from the strengths of the TiO bands and the depth of the bandhead of CO near 2.3 microns quantitatively confirm that the synthetic spectra are good representations of those of field M giants. The broad-band colors of the models match the field relations of K and early-M giants very well; for late-M giants, differences between the field-star and synthetic colors are probably caused by the omission of spectral lines of VO and water in the spectrum synthesis calculations. Here, we present four grids of K-band bolometric corrections and colors -- Johnson U-V and B-V; Cousins V-R and V-I; Johnson-Glass V-K, J-K and H-K; and CIT/CTIO V-K, J-K, H-K and CO -- for models having 3000 K < Teff < 4000 K and -0.5 < log g < 1.5. These grids, which have [Fe/H] = +0.25, 0.0, -0.5 and -1.0, extend and supplement the color-temperature relations of hotter stars presented in a companion paper (astro-ph/9911367).Comment: To appear in the March 2000 issue of the Astronomical Journal. 60 pages including 15 embedded postscript figures (one page each) and 6 embedded postscript tables (10 pages total

Population gene introgression and high genome plasticity for the zoonotic pathogen Streptococcus agalactiae

The influence that bacterial adaptation (or niche partitioning) within species has on gene spillover and transmission among bacteria populations occupying different niches is not well understood. Streptococcus agalactiae is an important bacterial pathogen that has a taxonomically diverse host range making it an excellent model system to study these processes. Here we analyze a global set of 901 genome sequences from nine diverse host species to advance our understanding of these processes. Bayesian clustering analysis delineated twelve major populations that closely aligned with niches. Comparative genomics revealed extensive gene gain/loss among populations and a large pan-genome of 9,527 genes, which remained open and was strongly partitioned among niches. As a result, the biochemical characteristics of eleven populations were highly distinctive (significantly enriched). Positive selection was detected and biochemical characteristics of the dispensable genes under selection were enriched in ten populations. Despite the strong gene partitioning, phylogenomics detected gene spillover. In particular, tetracycline resistance (which likely evolved in the human-associated population) from humans to bovine, canines, seals, and fish, demonstrating how a gene selected in one host can ultimately be transmitted into another, and biased transmission from humans to bovines was confirmed with a Bayesian migration analysis. Our findings show high bacterial genome plasticity acting in balance with selection pressure from distinct functional requirements of niches that is associated with an extensive and highly partitioned dispensable genome, likely facilitating continued and expansive adaptation

A two-domain elevator mechanism for sodium/proton antiport

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general

The FeH Wing-Ford Band in Spectra of M Stars

We study the FeH Wing-Ford band at 9850 - 10200 Angstrons by means of the fit of synthetic spectra to the observations of M stars, employing recent model atmospheres. On the basis of the spectrum synthesis, we analyze the dependence of the band upon atmospheric parameters. FeH lines are a very sensitive surface gravity indicator, being stronger in dwarfs. They are also sensitive to metallicity (Allard & Hauschildt 1995). The blending with CN lines, which are stronger in giants, does not affect the response of the Wing-Ford band to surface gravity at low resolution (or high velocity dispersions) because CN lines, which are spread all along the spectrum, are smeared out at convolutions of FWHM \simgreat 3 Angstrons. We conclude that the Wing-Ford band is a suitable dwarf/giant indicator for the study of composite stellar populations.Comment: 23 pages + 11 figures in postscript format + 3 ps figures (Nos. 2, 6 and 7) available under request to [email protected]. Accepted for publication in The Astrophysical Journa