bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updating in Response to the Experience of Lacking Knowledge
Authors: Pazy Asya 
Published: June 2004

Cette étude considère que la mise à jour professionnelle est un exemple d’apprentissage adulte autorégulé. Elle explore les relations entre le comportement de mise à jour et les variables phénoménologiques représentées par trois facteurs en rapport avec l’apprentissage: l’environnement, la cognition et la motivation/affectivité. 75 ingénieurs de l’industrie israélienne de haute technologie ont décrit de façon détaillée des incidents où ils ressentirent un manque de connaissances. L’analyse de contenu de ces témoignages a détecté les dimensions phénoménologiques de première importance que sont l’environnement, la cognition et la motivation/affectivité dans les expériences de lacunes de connaissances. La relation entre ces dimensions et la description d’une conduite de mise à jour a étéétudiée grâce à une analyse de régression logistique. L’analyse montra que les données correspondaient significativement au modèle. En particulier, la probabilité d’apparition d’un comportement de mise à jour était plus forte quand le manque de connaissance était éprouvé lors d’une tâche (et non lors d’une réunion), quand il stimulait un besoin d’apprendre, quand l’intéressé l’attribuait à une négligence antérieure et quand, exprimé par le comportement, il était transparent pour autrui. On expose en quoi ces résultats peuvent encourager l’apprentissage individuel dans les organisations.This study examines the relationships between updating behavior and variables that represent key learning‐related factors—context, cognition, and motivation/affect—as they are described in the lack of knowledge experience. Seventy‐five technical professionals employed in the Israeli high‐tech industry described in detail incidents in which they lacked knowledge. Analysis revealed that updating behavior was higher when lack of knowledge was experienced in the course of task performance (more than during a meeting). Updating was associated with learning motivation. It occurred when the lack of knowledge was visible to others through one's behavior, and when the individual attributed this lack to past avoidance. Implications of these findings for supporting individual learning in organisations are discussed.
Summer vegetation, deglaciation and the anomalous bird diversity gradient in eastern North America
Authors: Hawkins Bradford A. 
Published: June 2004

ABSTRACTAim  Geographic variation in the species richness of birds has been shown to be strongly associated with annual water and energy levels (actual evapotranspiration, AET) at the global scale. However, the gradient in eastern North America appears to be anomalous, because richness is greatest around the Great Lakes, whereas AET is highest in the south‐eastern US. Here I examine if birds may be responding to vegetation produced during the breeding season rather than to annual production.Location  North America east of longitude 98° W.Methods  The bird richness pattern was examined using climatic variables, remotely sensed estimates of annual and seasonal plant biomass, and time since areas were exposed by the retreating Laurentide ice sheet from 20,000 to 6000 yr bp.Results  Average summer GVI (Global Vegetation Index, derived from NDVI) was found to be positively linearly associated with richness, explaining 82% of the variance, whereas the relationships between richness and annual measures of both AET and GVI were curvilinear. The pattern of retreat of the Laurentide ice sheet explained an additional 6% of the variance in richness, consistent with a previous analysis of Canadian birds.Main conclusions  In eastern North America, a seasonal variable associated with plant production explains the diversity gradient rather than the annual measures, but it does not undermine a general conclusion that bird diversity is closely linked with plant biomass. Further, both contemporary and historical factors appear to influence the gradient, and an association between bird richness and the geographic pattern of glacial retreat is detectable in both climatic and plant‐biomass models of bird diversity.
Higher Education Outcomes, Graduate Employment and University Performance Indicators
Authors: Bratti Massimiliano , McKnight Abigail , Naylor Robin , Smith Jeremy 
Published: June 2004

SummaryOfficial employment-related performance indicators in UK higher education are based on the population of students responding to the ‘First destination supplement’ (FDS). This generates potentially biased performance indicators as this population of students is not necessarily representative of the full population of leavers from each institution. University leavers who do not obtain qualifications and those who do not respond to the FDS are not included within the official analysis. We compare an employment-related performance indicator based on those students who responded to the FDS with alternative approaches which address the potential non-random nature of this subgroup of university leavers.
An Overview of Risk-Adjusted Charts
Authors: Grigg O. , Farewell V. 
Published: June 2004

SummaryThe paper provides an overview of risk-adjusted charts, with examples based on two data sets: the first consisting of outcomes following cardiac surgery and patient factors contributing to the Parsonnet score; the second being age–sex-adjusted death-rates per year under a single general practitioner. Charts presented include the cumulative sum (CUSUM), resetting sequential probability ratio test, the sets method and Shewhart chart. Comparisons between the charts are made. Estimation of the process parameter and two-sided charts are also discussed. The CUSUM is found to be the least efficient, under the average run length (ARL) criterion, of the resetting sequential probability ratio test class of charts, but the ARL criterion is thought not to be sensible for comparisons within that class. An empirical comparison of the sets method and CUSUM, for binary data, shows that the sets method is more efficient when the in-control ARL is small and more efficient for a slightly larger range of in-control ARLs when the change in parameter being tested for is larger. The Shewart p-chart is found to be less efficient than the CUSUM even when the change in parameter being tested for is large.
Simultaneous Modelling of Multiple Traffic Safety Performance Indicators by using a Multivariate Generalized Linear Mixed Model
Authors: Bailey Trevor C. , Hewson Paul J. 
Published: June 2004

SummaryTraffic safety in the UK is one of the increasing number of areas where central government sets targets based on ‘outcome-focused’ performance indicators (PIs). Judgments about such PIs are often based solely on rankings of raw indicators and simple league tables dominate centrally published analyses. There is a considerable statistical literature examining health and education issues which has tended to use the generalized linear mixed model (GLMM) to address variability in the data when drawing inferences about relative performance from headline PIs. This methodology could obviously be applied in contexts such as traffic safety. However, when such models are applied to the fairly crude data sets that are currently available, the interval estimates generated, e.g. in respect of rankings, are often too broad to allow much real differentiation between the traffic safety performance of the units that are being considered. Such results sit uncomfortably with the ethos of ‘performance management’ and raise the question of whether the inference from such data sets about relative performance can be improved in some way. Motivated by consideration of a set of nine road safety performance indicators measured on English local authorities in the year 2000, the paper considers methods to strengthen the weak inference that is obtained from GLMMs of individual indicators by simultaneous, multivariate modelling of a range of related indicators. The correlation structure between indicators is used to reduce the uncertainty that is associated with rankings of any one of the individual indicators. The results demonstrate that credible intervals can be substantially narrowed by the use of the multivariate GLMM approach and that multivariate modelling of multiple PIs may therefore have considerable potential for introducing more robust and realistic assessments of differential performance in some contexts.
Statistical Issues in the Prospective Monitoring of Health Outcomes Across Multiple Units
Authors: Marshall Clare , Best Nicky , Bottle Alex , Aylin Paul 
Published: June 2004

SummaryFollowing several recent inquiries in the UK into medical malpractice and failures to deliver appropriate standards of health care, there is pressure to introduce formal monitoring of performance outcomes routinely throughout the National Health Service. Statistical process control (SPC) charts have been widely used to monitor medical outcomes in a variety of contexts and have been specifically advocated for use in clinical governance. However, previous applications of SPC charts in medical monitoring have focused on surveillance of a single process over time. We consider some of the methodological and practical aspects that surround the routine surveillance of health outcomes and, in particular, we focus on two important methodological issues that arise when attempting to extend SPC charts to monitor outcomes at more than one unit simultaneously (where a unit could be, for example, a surgeon, general practitioner or hospital): the need to acknowledge the inevitable between-unit variation in ‘acceptable’ performance outcomes due to the net effect of many small unmeasured sources of variation (e.g. unmeasured case mix and data errors) and the problem of multiple testing over units as well as time. We address the former by using quasi-likelihood estimates of overdispersion, and the latter by using recently developed methods based on estimation of false discovery rates. We present an application of our approach to annual monitoring ‘all-cause’ mortality data between 1995 and 2000 from 169 National Health Service hospital trusts in England and Wales.
Statistical Analysis of Performance Indicators in UK Higher Education
Authors: Draper David , Gittoes Mark 
Published: June 2004

SummaryAttempts to measure the quality with which institutions such as hospitals and universities carry out their public mandates have gained in frequency and sophistication over the last decade. We examine methods for creating performance indicators in multilevel or hierarchical settings (e.g. students nested within universities) based on a dichotomous outcome variable (e.g. drop-out from the higher education system). The profiling methods that we study involve the indirect measurement of quality, by comparing institutional outputs after adjusting for inputs, rather than directly attempting to measure the quality of the processes unfolding inside the institutions. In the context of an extended case-study of the creation of performance indicators for universities in the UK higher education system, we demonstrate the large sample functional equivalence between a method based on indirect standardization and an approach based on fixed effects hierarchical modelling, offer simulation results on the performance of the standardization method in null and non-null settings, examine the sensitivity of this method to the inadvertent omission of relevant adjustment variables, explore random-effects reformulations and characterize settings in which they are preferable to fixed effects hierarchical modelling in this type of quality assessment and discuss extensions to longitudinal quality modelling and the overall pros and cons of institutional profiling. Our results are couched in the language of higher education but apply with equal force to other settings with dichotomous response variables, such as the examination of observed and expected rates of mortality (or other adverse outcomes) in investigations of the quality of health care or the study of retention rates in the workplace.
Glycosaminoglycan‐dependent and ‐independent inhibition of neurite outgrowth by agrin
Authors: Baerwald‐De La Torre Kristine , Winzen Uwe , Halfter Willi , Bixby John L. 
Published: June 2004

AbstractAgrin is a proteoglycan that can inhibit neurite outgrowth from multiple neuronal types when present as a substrate. Agrin's neurite inhibitory activity is confined to the N‐terminal segment of the protein (agrin N150), which contains heparan sulfate (HS) and chondroitin sulfate (CS) side chains. We have examined the activities of various purified recombinant agrin fragments and their glycosaminoglycan (GAG) side chains in neurite outgrowth inhibition. Inhibitory activity was tested using dissociated chick ciliary ganglion neurons or dorsal root ganglion explants growing on laminin or N‐cadherin. Initial experiments demonstrated that agrin N150 lacking GAG chains inhibited neurite outgrowth. Both halves of N150, each containing HS and/or CS side chains, could also inhibit neurite growth. Experiments using agrin fragments in which the GAG acceptor residues were mutated, or using agrin fragments purified from cells deficient in GAG synthesis, demonstrated that inhibition by the N‐terminal portion of N150 requires GAGs, but that inhibition from the C‐terminal part of N150 does not. Thus, the core protein or other types of glycosylation are important for inhibition from the more C‐terminal region. Our results suggest that there are two distinct mechanisms for neurite outgrowth inhibition by agrin, one that is GAG‐dependent and one that is GAG‐independent.
A single amino acid substitution in a proteasome subunit triggers aggregation of ubiquitinated proteins in stressed neuronal cells
Authors: Li Zongmin , Arnaud Lisette , Rockwell Patricia , Figueiredo‐Pereira Maria E. 
Published: June 2004

AbstractAccumulation of ubiquitinated proteins in inclusions is common to various neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis, although it occurs in selective neurons in each disease. The mechanisms generating such abnormal aggregates and their role in neurodegeneration remain unclear. Inclusions appear in familial and non‐familial cases of neurodegenerative disorders, suggesting that factors other than particular mutations contribute to protein accumulation and aggregation. Proteasome impairment triggered by aging or conditions such as oxidative stress may contribute to protein accumulation and aggregation in neurodegeneration. To test this hypothesis in mouse neuronal cells, we overexpressed a 20S proteasome β5 subunit with an active site mutation. The N‐terminal threonine to alanine substitution resulted in impairment of the chymotrypsin‐like activity, which is a rate‐limiting step in protein degradation by the proteasome. The Thr1Ala mutation was not lethal under homeostatic conditions. However, this single amino acid substitution significantly hypersensitized the cells to oxidative stress, triggering not only the accumulation and aggregation of ubiquitinated proteins, including synuclein, but also cell death. Our results demonstrate that this genetic manipulation of proteasome activity involving a single amino acid substitution causes the formation of protein aggregates in stressed neuronal cells independently of the occurrence of mutations in other cellular proteins. These results support the notion that proteasome disruption may be central to the development of familial as well as sporadic cases of neurodegeneration.
Phospholipid synthesis is decreased in neuronal tissue in a mouse model of Sandhoff disease
Authors: Buccoliero Rosaria , Bodennec Jacques , Van Echten‐Deckert Gerhild , Sandhoff Konrad , Futerman Anthony H. 
Published: June 2004

AbstractSandhoff disease is a progressive neurodegenerative disorder caused by mutations in the HEXB gene which encodes for the β‐subunit of β‐hexosaminidase A and B, resulting in ganglioside GM2 accumulation in the brain. We now demonstrate that phospholipid metabolism is altered in both cultured neurons and in brain tissue from a mouse model of Sandhoff disease, the Hexb–/– mouse. Metabolic labelling using [methyl‐14C]choline and l‐[3‐3H]serine demonstrated reduced incorporation of [methyl‐14C]choline into phospholipids in brain tissue but not in liver or spleen. Phospholipid mass was also reduced in brain. The activities of CTP : phosphocholine cytidylyltransferase (CCT) and phosphatidylserine synthase were also reduced in brain tissue from Hexb–/– mice, probably because of post‐translational modification as no changes were observed in levels of enzyme expression. The relevance of these findings to Sandhoff disease in human patients is strengthened by observations made over 30 years ago on autopsy tissue of Tay Sachs and Sandhoff disease patients, in which reduced phospholipid levels were observed. We suggest that changes in phospholipid metabolism are not simply because of loss of neuronal tissue as a result of degeneration but rather may cause degeneration, and we discuss the possible effects that changes in phospholipid metabolism could play in the neuropathophysiology of Sandhoff disease.
Environment‐ and mutation‐dependent aggregation behavior of Alzheimer amyloid β‐protein
Authors: Yamamoto Naoki , Hasegawa Kazuhiro , Matsuzaki Katsumi , Naiki Hironobu , Yanagisawa Katsuhiko 
Published: June 2004

AbstractThe deposition of amyloid β‐protein in the brain is a fundamental process in the development of Alzheimerís disease; however, the mechanism underlying aggregation of amyloid β‐protein remains to be determined. Here, we report that a membrane‐mimicking environment, generated in the presence of detergents or a ganglioside, is sufficient per se for amyloid fibril formation from soluble amyloid β‐protein. Furthermore, hereditary variants of amyloid β‐protein, which are caused by amyloid precursor protein gene mutations, including the Dutch (E693Q), Flemish (A692G) and Arctic (E693G) types, show mutually different aggregation behavior in these environments. Notably, the Arctic‐type amyloid β‐protein, in contrast to the wild‐type and other variant forms, shows a markedly rapid and higher level of amyloid fibril formation in the presence of sodium dodecyl sulfate or GM1 ganglioside. These results suggest that there are favorable local environments for fibrillogenesis of amyloid β‐protein.
Microglia release activators of neuronal proliferation mediated by activation of mitogen‐activated protein kinase, phosphatidylinositol‐3‐kinase/Akt and delta–Notch signalling cascades
Authors: Morgan Sarah C. , Taylor Deanna L. , Pocock Jennifer M. 
Published: June 2004

AbstractMicroglia, the resident macrophage of the brain, can release substances that aid neuronal development, differentiation and survival. We have investigated the effects of non‐activated microglia on the survival of cultured rat cerebellar granule neurones. Microglial‐conditioned medium, collected from primary rat microglial cultures, was used to treat 7‐day‐in‐vitro neurones, and neuronal viability and proliferation was assessed following a further 1 or 7 days in culture. Microglial‐conditioned medium enhanced neuronal survival by up to 50% compared with untreated neurones and this effect was completely abated by pretreatment of the microglia with l‐leucine methyl ester. The expression of the proliferation marker Ki‐67 increased in neuronal cultures treated with microglial‐conditioned medium suggesting enhanced proliferation of precursor neurones. Microglial‐induced neuronal proliferation could be attenuated by specific inhibition of mitogen‐activated protein kinase or phosphatidylinositol‐3‐kinase/Akt signalling pathways, and by selective fractionation and immunodepletion of the microglial‐conditioned medium. Activation of the Notch pathway was enhanced as antibody against the Notch ligand, delta‐1, prevented the microglial‐induced neuronal proliferation. These results show that microglia release stable neurotrophic factors that can promote neuronal precursor cell proliferation.
Differential contribution of plasmalemmal Na+/Ca2+ exchange isoforms to sodium‐dependent calcium influx and NMDA excitotoxicity in depolarized neurons
Authors: Kiedrowski Lech , Czyż Aneta , Baranauskas Gytis , Li Xiao‐Fang , Lytton Jonathan 
Published: June 2004

AbstractInhibition of Na+,K+‐ATPase during NMDA applications greatly increased NMDA‐induced excitotoxicity in primary cultures of forebrain neurons (FNs), but not in cerebellar granule cells (CGCs). Because Na+,K+‐ATPase inhibition promotes reversal of plasmalemmal Na+/Ca2+ exchangers, we compared the activities of reversed K+‐independent (NCX) and K+‐dependent (NCKX) Na+/Ca2+ exchangers in these cultures. To this end, we measured gramicidin‐induced and Na+‐dependent elevation in cytosolic [Ca2+] ([Ca2+]c) that represents Ca2+ influx via reversed NCX and NCKX; NCX activity was dissected out by removing external K+. The [Ca2+]c elevations mediated by NCX alone, and NCX plus NCKX combined, were 17 and 6 times more rapid in FNs than in CGCs, respectively. Northern blot analysis showed that FNs preferentially express NCX1 whereas CGCs expressed NCX3. Differences in expression of other isoforms (NCX2, NCKX2, NCKX3 and NCKX4) were less pronounced. We tested whether the NCX or NCKX family of exchangers contributes most to the toxic NMDA‐induced Ca2+ influx in depolarized neurons. We found that in FNs, inhibition of NCX alone was sufficient to significantly limit NMDA excitotoxicity, whereas in CGCs, inhibition of both NCX and NCKX was required. The data suggest that the high activity of NCX isoforms expressed in FNs, possibly NCX1, sensitizes these neurons to NMDA excitotoxicity.
The interaction of Bex and OMP reveals a dimer of OMP with a short half‐life
Authors: Koo Jae Hyung , Gill Stephanie , Pannell Lewis K. , Menco Bert Ph. M. , Margolis Joyce W. , Margolis Frank L. 
Published: June 2004

AbstractOlfactory marker protein (OMP) participates in the olfactory signal transduction pathway. This is evident from the behavioral and electrophysiological deficits of OMP‐null mice, which can be reversed by intranasal infection of olfactory sensory neurons with an OMP‐expressing adenovirus. Bex, brain expressed X‐linked protein, has been identified as a protein that interacts with OMP. We have now further characterized the interaction of OMP and Bex1/2 by in vitro binding assays and by immuno‐coprecipitation experiments. OMP is a 19 kDa protein but these immunoprecipitation studies have revealed the unexpected presence of a 38 kDa band in addition to the expected 19 kDa band. Furthermore, the 38 kDa form was preferentially co‐immunoprecipitated with Bex from cell extracts. In‐gel tryptic digestion, mass spectrometry, and two‐dimensional gel electrophoresis indicate that the 38 kDa protein behaves as a covalently cross‐linked OMP‐homodimer. The 38 kDa band was also identified in western blots of olfactory epithelium demonstrating its presence in vivo. The stabilities and subcellular localizations of the OMP‐monomer and ‐dimer were studied in transfected cells. These results demonstrated that the OMP‐dimer is much less stable than the monomer, and that while the monomer is present both in the nuclear and cytosolic compartments, the dimer is preferentially located in a Triton X‐100 insoluble cytoskeletal fraction. These novel observations led us to hypothesize that regulation of the level of the rapidly turning‐over OMP‐dimer and its interaction with Bex1/2 is critical for OMP function in sensory transduction.