Improving Hospital at Home for frail older people: insights from a quality improvement project to achieve change across regional health and social care sectors.

BACKGROUND: Against a background of rising numbers of frail older people, there is a need to improve quality and safety of services whilst containing costs. Improving patient outcomes requires change across hospital and community systems. Our objective was to change practice in order to deliver a Hospital at Home programme (admission avoidance and early supported discharge) for frail older people across a regional commissioning area. The programme, undertaken within the Northern, Eastern & Western Devon Clinical Commissioning Group (CCG) sub-localities of Exeter (population 120,000) and Woodbury, Exmouth and Budleigh Salterton (towns with populations of around 10,000), involved reconfiguration of existing services rather than being a stand-alone intervention. METHODS: Quality Improvement methodology, with hospital and community staff using Plan-Do-Study-Act (PDSA) cycles to implement and test service changes. OUTCOME MEASURES: 1) Discharge destination; 2) Length of stay; 3) Acute Community Team referrals. RESULTS: Against a backdrop of intense financial pressures, significant community bed closures, and difficult relations between hospital and community services, outcomes remained stable (discharge destination, length of hospital stay, and number of referrals to the community team). CONCLUSION: PDSA cycles enabled stakeholders across acute and community services to be involved, promoted a process of collaborative inquiry and ownership of findings, and improved motivation to act on results and produce change. Practitioners and managers seeking to improve the delivery of complex, cross-cutting services in other areas can learn from the experience of applying Quality Improvement methods reported here.

[Pattern formation in microcosm: the role of self-assembly in complex biological envelopes development].

The data on the development of pollen/spore walls (of sporoderm) were reconsidered in the light of our hypothesis regarding a considerable role of self-assembling processes in the formation of this complex pattern. The premises that (1) glycocalyx (cell surface coating) is a self-assembling colloidal solution, and that (2) exine, formed on a glycocalyx framework, appears as a result of the self-assembly of the biopolymer (sporopollenin microemulsion), were independently suggested by the authors of this paper (Gabarayeva, 1990, 1993; Hemsley et al., 1992). Afterwards a joint hypothesis has been worked out which interpreted the processes of sporoderm development through regularities of colloidal chemistry. It was shown that all of the successive developmental stages, seen in transmission electron microscope (TEM) in the course of pollen wall development, correspond to successive micelle mesophases of a colloidal solution of surface-active substances which self-assemble when their concentration increases. Such an interpretation implies that all of the microstructures, observed in mature pollen walls (granules; rods-columellae; hexagonally packed layers of rods; bilayers, separated with a gap) are somewhat like "stiff history" of their appearance as a micellar sequence, immortalized by chemically resistant sporopollenin. Since self-assembling processes have nonlinear, spasmodic character, and microstructures of pollen wall, mentioned above, are arranged, as a rule, in successive layers, it has been suggested that these layers of heterogeneous microstructures occur as a result of the abrupt phase transitions typical for self-assembling micellar systems.

New insights from MALDI-ToF MS, NMR, and GC-MS: mass spectrometry techniques applied to palynology.

The present study for the first time describes the application of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-ToF MS) to palynology. With an accessible mass range of up to about 350,000 Da at subpicomolar range, this technique is ideal for the characterisation of bio-macromolecules, such as sporopollenin, found in fossil and extant pollen and spore walls, which often can only be isolated in very small quantities. At this stage, the limited solubility of sporopollenin allows for the identification of sections of this biopolymer, but with the optimisation of MALDI-ToF matrices, further structure elucidation will become possible. Furthermore, gas chromatography-mass spectrometry (GC-MS) and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy data obtained from a number of experiments revealed that some previously reported data were misinterpreted. These results add support to the hypothesis that common plasticizers were wrongly described as sporopollenin compounds.

Knowledge-based model of a glucosyltransferase from the oral bacterial group of mutans streptococci.

Mutans streptococci glucosyltransferases catalyze glucosyl transfer from sucrose to a glucan chain. We previously identified an aspartyl residue that participates in stabilizing the glucosyl transition state. The sequence surrounding the aspartate was found to have substantial sequence similarity with members of alpha-amylase family. Because little is known of the protein structure beyond the amino acid sequence, we used a knowledge-based interactive algorithm, MACAW, which provided significant level of homology with alpha-amylases and glucosyltransferase from Streptococcus downei gtfI (GTF). The significance of GTF similarity is underlined by GTF/alpha-amylase residues conserved in all but one alpha-amylase invariant residues. Site-directed mutagenesis of the three GTF catalytic residues are homologous with the alpha-amylase catalytic triad. The glucosyltransferases are members of the 4/7-superfamily that have a (beta/alpha)8-barrel structure and belong to family 13 of the glycohydralases.

Comparison of a dengue-2 virus and its candidate vaccine derivative: sequence relationships with the flaviviruses and other viruses.

A comparison of the sequence of the dengue-2 16681 virus with that of the candidate vaccine strain (16681-PDK53) derived from it identified 53 of the 10,723 nucleotides which differed between the strains. Nucleotide changes occurred in genes coding for all virion and nonvirion proteins, and in the 5' and 3' untranslated regions. Twenty-seven of the nucleotide changes resulted in amino acid alterations. The greatest amino acid sequence differences in the virion proteins occurred in prM (2.20%; 2/91 amino acids) followed by the M protein (1.33%; 1/75 amino acids), the C protein (0.88%; 1/114 amino acid), and the E protein (0.61%; 3/495 amino acids). Differences in the amino acid sequence of nonvirion proteins ranged from 1.51% (6/398 amino acids) in NS4 to 0.33% (3/900 amino acids) in NS5. The encoded protein sequences of 16681-PDK53 were also compared with the published sequences of other flaviviruses to obtain a detailed classification of 17 flaviviruses using the neighbor-joining tree method. The analyses of the sequence data produced dendrograms which supported the traditional groupings based on serological evidence, and they suggested that the flaviviruses have evolved by divergent mutational change and there was no evidence of genetic recombination between members of the group. Comparisons of the sequences of the flavivirus polymerase and helicase-like proteins (NS5 and NS3, respectively) with those from other viruses yielded a classification of the flaviviruses indicating that the primary division of the flaviviruses was between those transmitted by mosquitoes and those transmitted by ticks.

A simple method for site-directed mutagenesis using the polymerase chain reaction.

We have developed a general and simple method for directing specific sequence changes in a plasmid using primed amplification by the polymerase chain reaction (PCR). The method is based on the amplification of the entire plasmid using primers that include the desired changes. The method is rapid, simple in its execution, and requires only minute amounts of plasmid template DNA. It is significant that there are no special requirements for appropriately placed restriction sites in the sequence to be manipulated. In our system the yield of transformants was high and the fraction of them harboring plasmids with only the desired change was consistently about 80%. The generality of the method should make it useful for the direct alteration of most cloned genes. The only limitation may be the total length of the plasmid to be manipulated. During the study we found that the Taq DNA polymerase used for PCR adds on a single extra base (usually an A) at the end of a large fraction of the newly synthesized chains. These had to be removed by the Klenow fragment of DNA polymerase to insure restoration of the gene sequence.

On the compartmentalization of catalase, fatty acyl-CoA oxidase and urate oxidase in mammalian livers, and the influence of clofibrate treatment on this microlocalization.

The compartmentalization of catalase, fatty acyl-CoA oxidase and urate oxidase was examined in the livers of mice, rats and guinea pigs, using the technique of digitonin extraction in order to avoid the trauma associated with centrifugation procedures. The results are interpreted as indicating that an appreciable proportion of catalase activity occurs in the cytoplasmic compartment of these cells. Following treatment of the animals with clofibrate, the specific activity in both peroxisomal and cytoplasmic compartments was increased, with a higher proportion of cytoplasmic catalase being evident in mice. The results for catalase were compared with those for fatty acyl-CoA oxidase and urate oxidase both of which were indicated as showing a closer association with the peroxisomal compartment than was the case for catalase. These data have been discussed in relation to their significance on present understanding of peroxisomal structure and function.

Purification of peroxisomes from livers of normal and clofibrate-treated mice.

A method for the isolation of peroxisomes from livers of normal and clofibrate-treated mice is described. The method utilizes glutaraldehyde to stabilize peroxisomal membranes, and isopycnic centrifugation of a light mitochondrial fraction through a linear metrizamide gradient to achieve optimal resolution from other organelles. On the basis of the biochemical and morphological data, the peroxisomal preparations are indicated as of high purity: contamination by mitochondria, lysosomes, and plasma membranes is negligible, and the level of contaminating microsomes is around 5% for normal peroxisomes and 8% for peroxisomes from clofibrate-treated mice. Peroxisomal membranes prepared by carbonate extraction contain two major polypeptides of approximately 70,000 Da, and show 2 and 8% contamination by microsomal membrane protein for the preparations from normal and clofibrate-treated mice, respectively.