The pursuit of excellence is not optional in the voluntary sector, it is essential.

This paper outlines the continuous improvement journey of a voluntary organisation. The significant level of organisational growth and improving quality of services described is clearly linked to the organisation's commitment to improvement. One of the approaches used in adopting a total quality culture was the EFQM model, specifically interpreted for the voluntary sector. Until recently such an approach would have been considered alien to the sector, not least because of its origins in the business community. This article contradicts this assumption. Issues addressed include how the improvement process is driven, the use of performance measurement, external verification and the difficulties in accessing sector appropriate benchmark data. It is suggested that the pursuit of excellence is no longer optional for the voluntary sector, it is essential.     

Structure of a quinohemoprotein amine dehydrogenase with an uncommon redox cofactor and highly unusual crosslinking

The crystal structure of the heterotrimeric quinohemoprotein amine dehydrogenase from Paracoccus denitrificans has been determined at 2.05-A resolution. Within an 82-residue subunit is contained an unusual redox cofactor, cysteine tryptophylquinone (CTQ), consisting of an orthoquinone-modified tryptophan side chain covalently linked to a nearby cysteine side chain. The subunit is surrounded on three sides by a 489-residue, four-domain subunit that includes a diheme cytochrome c. Both subunits sit on the surface of a third subunit, a 337-residue seven-bladed beta-propeller that forms part of the enzyme active site. The small catalytic subunit is internally crosslinked by three highly unusual covalent cysteine to aspartic or glutamic acid thioether linkages in addition to the cofactor crossbridge. The catalytic function of the enzyme as well as the biosynthesis of the unusual catalytic subunit is discussed.     

High-Throughput Variation Detection and Genotyping Using Microarrays

The genetic dissection of complex traits may ultimately require a large number of SNPs to be genotyped in multiple individuals who exhibit phenotypic variation in a trait of interest. Microarray technology can enable rapid genotyping of variation specific to study samples. To facilitate their use, we have developed an automated statistical method (ABACUS) to analyze microarray hybridization data and applied this method to Affymetrix Variation Detection Arrays (VDAs). ABACUS provides a quality score to individual genotypes, allowing investigators to focus their attention on sites that give accurate information. We have applied ABACUS to an experiment encompassing 32 autosomal and eight X-linked genomic regions, each consisting of approximately 50 kb of unique sequence spanning a 100-kb region, in 40 humans. At sufficiently high-quality scores, we are able to read approximately 80% of all sites. To assess the accuracy of SNP detection, 108 of 108 SNPs have been experimentally confirmed; an additional 371 SNPs have been confirmed electronically. To access the accuracy of diploid genotypes at segregating autosomal sites, we confirmed 1515 of 1515 homozygous calls, and 420 of 423 (99.29%) heterozygotes. In replicate experiments, consisting of independent amplification of identical samples followed by hybridization to distinct microarrays of the same design, genotyping is highly repeatable. In an autosomal replicate experiment, 813,295 of 813,295 genotypes are called identically (including 351 heterozygotes); at an X-linked locus in males (haploid), 841,236 of 841,236 sites are called identically.     

Endoscopic management of colorectal polyps: From benign to malignant polyps

Colorectal cancer(CRC) is the third most common cancer worldwide and the second leading cause of cancer related death in the world. The early detection and removal of CRC precursor lesions has been shown to reduce the incidence of CRC and cancer-related mortality. Endoscopic resection has become the first-line treatment for the removal of most precursor benign colorectal lesions and selected malignant polyps. Detailed lesion assessment is the first critical step in the evaluation and management of colorectal polyps. Polyp size, location and both macro-and micro-features provide important information regarding histological grade and endoscopic resectability. Benign polyps and even malignant polyps with superficial submucosal invasion and favorable histological features can be adequately removed endoscopically. When compared to surgery, endoscopic resection is associated with lower morbidity, mortality, and higher patient quality of life. Conversely, malignant polyps with deep submucosal invasion and/or high risk for lymph node metastasis will require surgery. From a practical standpoint,the most appropriate strategy for each patient will need to be individualized,based not only on polyp-and patient-related characteristics, but also on local resources and expertise availability. In this review, we provide a broad overview and present a potential decision tree algorithm for the evaluation and management of colorectal polyps that can be widely adopted into clinical practice.     

Downregulation of the inhibitor of apoptosis protein survivin in keratinocytes and endothelial cells in psoriasis skin following infliximab therapy

BACKGROUND: Survivin, an inhibitor of apoptosis protein (IAP), has been implicated in endothelial cell stability, through inhibition of apoptosis and in cell proliferation. OBJECTIVES: To evaluate the effect of antitumour necrosis factor (TNF)-alpha therapy on survivin expression in psoriasis skin at 0, 2 and 12 weeks after infliximab therapy. METHODS: Skin biopsies were obtained from 16 patients; 11 also had arthritis with active skin/joint disease. Clinical scores [Psoriasis Area and Severity Index (PASI), involved body surface area (BSA), Disease Activity Score (DAS28) and Health Assessment Questionnaire] were recorded. Inflammatory infiltration and survivin protein expression were examined and graded by immunohistochemical staining, and mRNA levels were determined by real-time polymerase chain reaction. RESULTS: Survivin mRNA and protein were demonstrated in all baseline lesional biopsies. Survivin mRNA and protein expression was significantly greater in lesional compared with nonlesional baseline skin (P < 0.05). Differential cellular localization of survivin was demonstrated with cytoplasmic survivin protein expression localized to the perivascular/endothelial regions and strong nuclear staining localized in the basal layer of the epidermis. Infliximab produced a dramatic clinical response in skin and joints (P < 0.05), paralleled by significant reduction in the inflammatory infiltrate and survivin protein expression (P < 0.05) which was reflected at the mRNA level where expression was significantly reduced by week 12 (P < 0.01). Survivin protein levels before and after treatment significantly correlated with PASI (r = 0.478, P < 0.05) and BSA scores (r = 0.528, P < 0.024). PASI strongly correlated with BSA (r = 0.949, P < 0.0001) and DAS28 (r = 0.717, P < 0.002) scores. CONCLUSIONS: Survivin correlates with disease activity in patients with psoriasis and is significantly downregulated following anti-TNF-alpha treatment. Understanding the role of IAPs in cell survival/antiapoptosis and proliferation mechanisms may provide important insights into downstream therapeutic targeting in inflammation.     

Uterine rupture in a multiparous woman during labor induction with oral misoprostol.

A multigravida with gestational diabetes, mild pregnancy-induced hypertension and a previous curettage received four doses of misoprostol (100 microg) at three hourly intervals for induction of labor at term. Vaginal delivery of a live healthy baby occurred 1 h after the fourth dose. Hindwaters were bloodstained. Three hours later, she had excessive bleeding. Examination showed that the left lateral uterine wall had ruptured. She recovered after hysterectomy and blood transfusions.     

Compartment syndrome of the well leg as a result of the hemilithotomy position: a report of two cases and review of literature.

Compartment syndrome in the well leg as a complication of prolonged positioning in a hemilithotomy position is a serious complication that is rarely reported in the orthopaedic literature. A similar entity has been well described in urologic, gynecologic, and general surgery literature but, to the authors' knowledge, has been reported in only seven patients in the orthopaedic literature. The authors report two cases of unilateral compartment syndrome in a well leg during femoral nailing of the contralateral leg. Risk factors, theories of pathogenesis, and preventive measures are identified and discussed.     

The natural history of renal disease in Australian Aborigines. Part 1. Changes in albuminuria and glomerular filtration rate over time.

BACKGROUND: The purpose of this study was to describe changes over time in albuminuria and glomerular filtration rate (GFR) in a cohort of Australian Aborigines from a community with high rates of renal disease and renal failure. METHODS: Participants were 486 adult community members (20+ years at first exam) who were screened for renal disease and related factors on at least two occasions (mean 2.7 occasions), at least a year apart, between 1990 and 1997. Renal function was assessed by the albumin:creatinine ratio (ACR; g/mol) on a random urine specimen and by the GFR estimated from the Cockcroft-Gault formula. Evolution over time was expressed as the average annual changes in these parameters. RESULTS: On baseline examination, 70% of participants had albuminuria (ACR 1.1+ g/mol) There was a significant net increase in ACR and a fall in GFR in the cohort over time. Among individuals, however, changes were strongly correlated with ACR levels at baseline. There was no loss of GFR in persons with normal renal parameters at baseline and a rapid loss of GFR in those with substantial levels of albuminuria at baseline. Other factors significantly correlated with progression of ACR included age, baseline body mass index and systolic blood pressure, the presence of diabetes (or levels of fasting glucose), and elevated levels of serum gamma glutamyl transferase. Factors significantly associated with loss of GFR included body mass index, diabetes, systolic and diastolic blood pressures, microscopic hematuria, and marginally high cholesterol levels. CONCLUSION: Albuminuria progresses and GFR is lost over time in individuals in this community, at rates that are strongly dependent on levels of pre-existing albuminuria. Much loss of GFR and all renal failure should be avoided by preventing the development of albuminuria and minimizing its progression. This depends on improving the weight, blood pressure, and metabolic profile of the entire community and reducing infections. Modification of the course in people with established disease depends on vigorous control of blood pressure and the metabolic profile and the specific use of angiotensin-converting enzyme inhibitors.