What can trauma patients' experiences and perspectives tell us about the perceived quality of trauma care? a qualitative study set within the UK National Health Service.

The global drive for improvements in the efficiency and quality of healthcare has led to the development of frameworks to assist in defining and measuring 'good quality care'. However, such frameworks lack a systematic or meaningful definition of what 'good quality care' means from the patients' perspective. The present research provides an in-depth analysis of patients' experiences in a hospital setting from a quality of care perspective. Forty-five adults (aged 16-70) hospitalised in one of four UK NHS trusts following an unintentional injury were interviewed about their experiences of care. The findings show variability in perceived quality of care within the same hospital episode which cannot be meaningfully captured by existing frameworks. The context of trauma care (e.g. distressing nature of injury, patient vulnerability, expectations of hospitalisation and participants' interaction with different service providers) defined the care experience and the value of being 'cared for'. Participants identified some aspects of good and care which related to holistic, person-centred and personalised care beyond the medical needs. Participants discussed the value of being understood, staff thinking of their needs beyond hospitalisation, staff trying 'their best' despite constrains of current care, having their emotional needs recognised and addressed and staff competence. Patients reported also poor quality of care and 'not being cared for' by specific staff groups which they expected to fulfil this role, rushed and unsympathetic care, lack of recognition for emotional impact of injury mapped onto existing quality frameworks e.g. safety, equity, accessibility and patient-centeredness as well as quality of interaction with providers, empathetic care which extended beyond medical needs, coordination of care, and the positivity of care delivery as important dimensions of quality care with implications for their recovery. The findings have implications for quality frameworks and theoretical definitions of quality of care; they demonstrate the importance of patient experience in addition to clinical effectiveness and safety as an essential dimension of quality care. In terms of practice, the findings support the need to incorporate knowledge and training of injured adults' psychological needs, and the value of interaction with professionals as a patient defined dimension of the quality of care.

Different pathways of molecular pathophysiology underlie cognitive and motor tauopathy phenotypes in transgenic models for Alzheimer's disease and frontotemporal lobar degeneration.

A poorly understood feature of the tauopathies is their very different clinical presentations. The frontotemporal lobar degeneration (FTLD) spectrum is dominated by motor and emotional/psychiatric abnormalities, whereas cognitive and memory deficits are prominent in the early stages of Alzheimer's disease (AD). We report two novel mouse models overexpressing different human tau protein constructs. One is a full-length tau carrying a double mutation [P301S/G335D; line 66 (L66)] and the second is a truncated 3-repeat tau fragment which constitutes the bulk of the PHF core in AD corresponding to residues 296-390 fused with a signal sequence targeting it to the endoplasmic reticulum membrane (line 1; L1). L66 has abundant tau pathology widely distributed throughout the brain, with particularly high counts of affected neurons in hippocampus and entorhinal cortex. The pathology is neuroanatomically static and declines with age. Behaviourally, the model is devoid of a higher cognitive phenotype but presents with sensorimotor impairments and motor learning phenotypes. L1 displays a much weaker histopathological phenotype, but shows evidence of neuroanatomical spread and amplification with age that resembles the Braak staging of AD. Behaviourally, the model has minimal motor deficits but shows severe cognitive impairments affecting particularly the rodent equivalent of episodic memory which progresses with advancing age. In both models, tau aggregation can be dissociated from abnormal phosphorylation. The two models make possible the demonstration of two distinct but nevertheless convergent pathways of tau molecular pathogenesis. L1 appears to be useful for modelling the cognitive impairment of AD, whereas L66 appears to be more useful for modelling the motor features of the FTLD spectrum. Differences in clinical presentation of AD-like and FTLD syndromes are therefore likely to be inherent to the respective underlying tauopathy, and are not dependent on presence or absence of concomitant APP pathology.

Health evaluation of penguins (Sphenisciformes) following mortality in the Falklands (South Atlantic).

In the Falklands, heavy mortality of rock-hopper penguins Eudyptes chrysocome occurred during the 1985-86 breeding season. Starvation was diagnosed as the primary cause of death, possibly caused by a shortage of euphausiid crustaceans (krill) due to unusual meterological conditions. 'Puffinosis' may possibly have been a contributory factor; otherwise no conclusive evidence of infectious disease or toxicosis was found and also no evidence of radioactive contamination. In the 1986-87 breeding season no unusual mortality occurred, but 99 apparently healthy penguins were examined, i.e., rockhoppers Eudyptes chrysocome syn E. crestatus, gentoos Pygoscelis papua and Magellanics Spheniscus magellanicus. Full necropsies were carried out on 54. Tissue examinations were made for cadmium, copper, iron, manganese, mercury, lead and zinc. High tissue cadmium concentrations found in healthy birds in 1987 were similar to those in penguins which died in 1986, and therefore not considered to be of pathological significance. Although there has been no repetition of the unusually hot 1985-86 breeding season in the Falklands, penguins and other seabirds have had fluctuating breeding successes since then. The precise cause, including the roles of meteorological conditions and overexploitation of some forms of prey species, is unclear.

The gene and pseudogenes of Cbx3/mHP1 gamma.

The HP1 class of chromobox (Cbx) genes encode an evolutionarily conserved family of proteins involved in the packaging of chromosomal domains into a repressive heterochromatic state. The murine Cbx5, Cbx1 and Cbx3 genes encode the three mouse HP1 proteins, mHP1 alpha, -beta and -gamma respectively. Here, we report the cloning of the mouse Cbx3/HP1 gamma gene and the chromosomal localisation of Cbx3 and three Cbx3-related pseudogenes. The Cbx3 structural gene is located on mouse Chromosome 6, close to the Hoxa cluster. Two Cbx3 processed pseudogenes are separated by just 300 bp and are arranged in a head-to-tail configuration on Chromosome 13 while a third pseudogene is found on mouse Chromosome 4. The genomic intron-exon arrangement of Cbx3 is different from the conserved organisation of three other mammalian HP1 genes, Cbx1 (mHP1 beta), CBX3 (hHP1 gamma), and Cbx5 (mHP1 alpha) in that Cbx3 lacks an intron that is present in the others.

Conservation of heterochromatin protein 1 function.

Heterochromatin represents a cytologically visible state of heritable gene repression. In the yeast, Schizosaccharomyces pombe, the swi6 gene encodes a heterochromatin protein 1 (HP1)-like chromodomain protein that localizes to heterochromatin domains, including the centromeres, telomeres, and the donor mating-type loci, and is involved in silencing at these loci. We identify here the functional domains of swi6p and demonstrate that the chromodomain from a mammalian HP1-like protein, M31, can functionally replace that of swi6p, showing that chromodomain function is conserved from yeasts to humans. Site-directed mutagenesis, based on a modeled three-dimensional structure of the swi6p chromodomain, shows that the hydrophobic amino acids which lie in the core of the structure are critical for biological function. Gel filtration, gel overlay experiments, and mass spectroscopy show that HP1 proteins can self-associate, and we suggest that it is as oligomers that HP1 proteins are incorporated into heterochromatin complexes that silence gene activity.

The M31 gene has a complex developmentally regulated expression profile and may encode alternative protein products that possess diverse subcellular localisation patterns.

HP1-like chromobox genes comprise an evolutionarily conserved family of genes that encode components of centromeric heterochromatin. In order to investigate the role of the murine HP1-like gene, M31, in heterochromatin formation we have isolated its gene and characterised its transcripts and protein products. PCR products that represent M31 transcripts were detected at the one-cell stage and were maternal in origin. Maternal provision of M31 transcripts may reflect a need for M31 in the formation of a functional centromere in order that there is proper segregation of chromosomes during the early cleavage divisions; studies in fission yeast and Drosophila have suggested a crucial role for HP1-like genes in centromere function. There are three protein products encoded by the M31 gene. Surprisingly, the two smaller products are found almost exclusively in the cytoplasm.

M32, a murine homologue of Drosophila heterochromatin protein 1 (HP1), localises to euchromatin within interphase nuclei and is largely excluded from constitutive heterochromatin.

Mice possess two structural homologues of Drosophila HP1, termed M31 and M32 (Singh et al., 1991). We have previously shown that an M31-specific monoclonal antibody (MoAb), MAC 353, localises to constitutive heterochromatin (Wreggett et al., 1994). Here we report that a MoAb raised against the M32 protein (MAC 385) recognises a 22-kDa protein in murine nuclear extracts and that M32 is distributed in a fine-grain "speckled" pattern within interphase nuclei. M32 is also largely excluded from the large masses of constitutive heterochromatin that are labelled by MAC 353.

Platelet activating factor antagonist design. 3. X-ray crystal structure and intermolecular crystal lattice interactions of methyl trans-4-acetoxymethyl-4,5-dihydro-2,5-bis(3,4-methylenedioxyphenyl)- 3-furancarboxylate.

C23H20O9, Mr = 440.41, monoclinic, P21/c, a = 11.433 (1), b = 7.808 (2), c = 23.313 (3) A, beta = 99.67 (1) degree, V = 2052 A3, Z = 4, Dx = 1.43 g cm-3, lambda(MoK alpha) = 0.71073 A, mu = 0.69 cm-1, F(000) = 920, T = 293 K, final R = 0.048 for 1645 observed [Fo greater than or equal to 5 sigma(Fo)] reflections. The observed structure reveals a trans relationship for the 4-acetoxymethyl and 5-aryl substituents. The 4,5-dihydrofuran ring system adopts an envelope conformation. There is no crystallographically imposed symmetry. Several intermolecular van der Waals interactions occur in the cell lattice of this compound.

Haematology of wild penguins (spenisciformes) in the Falkland Islands.

Haematological values were determined in 50 Rockhopper (Eudyptes crestatus), 19 Gentoo (Pygoscelis papua) and 12 Magellanic (Spheniscus magellanicus) penguins from various sites on the Falkland Islands. Adult Magellanic penguins had significantly lower haemoglobin (Hb) levels, packed cell volumes (PCV) and red cell counts (RBC) than adults of the other two species. Hb, PCV and RBC values were also lower in juvenile birds than in adults and lower in post-moult than in pre-moult adults. Comparison of findings in wild Rockhopper and Gentoo penguins with values obtained from captive birds showed slight but significant differences in Hb and mean cell haemoglobin concentration, and in the relative numbers of heterophils, lymphocytes, monocytes and eosinophils present.

Plasma alpha-tocopherol, total lipids and total cholesterol in wild rockhopper, magellanic and gentoo penguins before and after moulting.

Post moult rockhopper penguins (Eudyptes crestatus) had significantly higher plasma alpha-tocopherol (vitamin E), total lipid and total cholesterol concentrations than their pre-moult counterparts. In the magellanic penguins (Spheniscus magellanicus) there were post moult increases in total lipid, cholesterol and alpha-tocopherol concentrations, but only the increase in alpha-tocopherol was significant. Plasma alpha-tocopherol, total lipid and total cholesterol concentrations in post moult gentoo (Pygoscelis papua) chicks were similar to those in non-moulting adult gentoos. Species differences in the levels of these nutrients in plasma may be due to differences in their dietary habits.

Antibodies to brain clathrin recognise plant coated vesicles.

Coated vesicles isolated from carrot suspension culture cells were immune-blotted against four antibodies to porcine brain clathrin. Positive cross-reaction was obtained with three antibodies. Two of these cross-reacted with both the heavy clathrin chain and the putative light chains. Three out of five antibodies immunofluorescently stained permeabilised carrot suspension culture cells.