A framework for using business excellence models for performance improvement at operational level.

It is important that manufacturing organisations are able to measure their performance in a way that will enable them to better manage their organisation to achieve competitive advantage. This paper argues that there are already appropriate methodologies that have been developed for this purpose, namely self-assessment against quality awards and business excellence models. Subject to development to overcome their weaknesses, these can be used for measuring manufacturing performance at an operational level. The research reported here outlines the development of such a framework and its successful application to a case example of a manufacturing facility in the UK

Self Assessment: use at operational level to promote continuous improvement.

The European Foundation for Quality Management (EFQM) Excellence 2000 Model is widely adopted by organizations as a means of self-assessment to enhance performance. This self-assessment has focussed mainly on the company or strategic level, but it is argued here that the self-assessment process can be modified to more appropriately suit the different needs of continual improvement at an operational or departmental level. This paper reports a generic process, applicable to the majority of situations, whereby self-assessment can be developed to meet the continual improvement needs of individual departments. The development process involves the application of Grounded Theory Learning Activities to generate a set of departmentally relevant constructs or issues which are then reviewed against a simple five-step model of self-assessment to determine the most appropriate departmental approach. The process is illustrated through a case application showing the use of the methodology

Novel O-palmitolylated beta-E1 subunit of pyruvate dehydrogenase is phosphorylated during ischemia/reperfusion injury

<p>Abstract</p> <p>Background</p> <p>During and following myocardial ischemia, glucose oxidation rates are low and fatty acids dominate as a source of oxidative metabolism. This metabolic phenotype is associated with contractile dysfunction during reperfusion. To determine the mechanism of this reliance on fatty acid oxidation as a source of ATP generation, a functional proteomics approach was utilized.</p> <p>Results</p> <p>2-D gel electrophoresis of mitochondria from working rat hearts subjected to 25 minutes of global no flow ischemia followed by 40 minutes of aerobic reperfusion identified 32 changes in protein abundance compared to aerobic controls. Of the five proteins with the greatest change in abundance, two were increased (long chain acyl-coenzyme A dehydrogenase (48 ± 1 versus 39 ± 3 arbitrary units, n = 3, P < 0.05) and α subunit of ATP synthase (189 ± 15 versus 113 ± 23 arbitrary units, n = 3, P < 0.05)), while two were decreased (24 kDa subunit of NADH-ubiquinone oxidoreductase (94 ± 7 versus 127 ± 9 arbitrary units, n = 3, P < 0.05) and D subunit of ATP synthase (230 ± 11 versus 368 ± 47 arbitrary units, n = 3, P < 05)). Two forms of pyruvate dehydrogenase βE1 subunit, the rate-limiting enzyme for glucose oxidation, were also identified. The protein level of the more acidic form of pyruvate dehydrogenase was reduced during reperfusion (37 ± 4 versus 56 ± 7 arbitrary units, n = 3, P < 05), while the more basic form remained unchanged. The more acidic isoform was found to be O-palmitoylated, while both isoforms exhibited ischemia/reperfusion-induced phosphorylation. <it>In silico </it>analysis identified the putative kinases as the insulin receptor kinase for the more basic form and protein kinase Cζ or protein kinase A for the more acidic form. These modifications of pyruvate dehydrogenase are associated with a 35% decrease in glucose oxidation during reperfusion.</p> <p>Conclusions</p> <p>Cardiac ischemia/reperfusion induces significant changes to a number of metabolic proteins of the mitochondrial proteome. In particular, ischemia/reperfusion induced the post-translational modification of pyruvate dehydrogenase, the rate-limiting step of glucose oxidation, which is associated with a 35% decrease in glucose oxidation during reperfusion. Therefore these post-translational modifications may have important implications in the regulation of myocardial energy metabolism.</p

Book reviews

Title: Geriatrics (Guidelines in Medicine — Vo.1) Authors: A.N. Exton-Smith, P.W. Overstall. Publishers: MTP Press Limited. Pages 344. Publication Date: 1979Title: The M.R.C.G.P. Examination. Authors: A.J. Moulds, T.A. Bouchier Hayes &amp; K.H.M. Young. Publishers: M.T.P. Press Limited, International Medical Publishers. Pages 131. publication Date: November 1978. Price: £4.95Title: Local Analgesia — 2nd edition. Author: Dr. Clive Jolly. Publishers: H.K. Lewis &amp; Co. Ltd., London. Pages: 152 (illusr. — 19) Publication date: 1979. Price: £5.00 net

^(13)CH_3OH in OMC-1

We report the identification of several previously unidentified or misidentified lines toward OMC-1 as components the J = 5 → 4 α-type band of ^(13)CH_30H, deduced by combining accurate laboratory spectroscopy with sensitive broad-band astronomical line searches. An LTE fit to the data yields a rotational temperature of T_(rot)~ 120 K and a ^(13)CH_30H column density of ~1.3 x 10^(15) cm^(-2), averaged over a 30" beam. A ^(12)C/^(13)C ratio of ~30 is derived. The assignment of the feature at 236063 MHz to the blended K = ±2 E transitions of ^(13)CH_30H, rather than to CO^+, removes a major discrepancy between observation and the predictions of ion-molecule chemical models of dense interstellar clouds

Prednisolone or pentoxifylline for alcoholic hepatitis

BACKGROUND: Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists.METHODS: We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline.RESULTS: A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002).CONCLUSIONS: Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Antarctic last interglacial isotope peak in response to sea ice retreat not ice-sheet collapse

Several studies have suggested that sea-level rise during the last interglacial implies retreat of the West Antarctic Ice Sheet (WAIS). The prevalent hypothesis is that the retreat coincided with the peak Antarctic temperature and stable water isotope values from 128,000 years ago (128 ka); very early in the last interglacial. Here, by analysing climate model simulations of last interglacial WAIS loss featuring water isotopes, we show instead that the isotopic response to WAIS loss is in opposition to the isotopic evidence at 128 ka. Instead, a reduction in winter sea ice area of 65±7% fully explains the 128 ka ice core evidence. Our finding of a marked retreat of the sea ice at 128 ka demonstrates the sensitivity of Antarctic sea ice extent to climate warming