bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of the Homotypic Fusion and Vacuole Protein Sorting or Golgi-Associated Retrograde Protein Vesicle Tethering Complexes Results in Gentamicin Sensitivity in the Yeast
Saccharomyces cerevisiae
Authors: Wagner Mark C. , Molnar Elizabeth E. , Molitoris Bruce A. , Goebl Mark G.
Published: January 2006

Gentamicin continues to be a primary antibiotic against gram-negative infections. Unfortunately, associated nephro- and ototoxicity limit its use. Our previous mammalian studies showed that gentamicin is trafficked to the endoplasmic reticulum in a retrograde manner and subsequently released into the cytosol. To better dissect the mechanism through which gentamicin induces toxicity, we have chosen to study its toxicity using the simple eukaryote
Saccharomyces cerevisiae
. A recent screen of the yeast deletion library identified multiple gentamicin-sensitive strains, many of which participate in intracellular trafficking. Our approach was to evaluate gentamicin sensitivity under logarithmic growth conditions. By quantifying growth inhibition in the presence of gentamicin, we determined that several of the sensitive strains were part of the Golgi-associated retrograde protein (GARP) and homotypic fusion and vacuole protein sorting (HOPS) complexes. Further evaluation of their other components showed that the deletion of any GARP member resulted in gentamicin-hypersensitive strains, while the deletion of other HOPS members resulted in less gentamicin sensitivity. Other genes whose deletion resulted in gentamicin hypersensitivity included
ZUO1
,
SAC1
, and
NHX1
. Finally, we utilized a Texas Red gentamicin conjugate to characterize gentamicin uptake and localization in both gentamicin-sensitive and -insensitive strains. These studies were consistent with our mammalian studies, suggesting that gentamicin toxicity in yeast results from alterations to intracellular trafficking pathways. The identification of genes whose absence results in gentamicin toxicity will help target specific pathways and mechanisms that contribute to gentamicin toxicity.
In Vivo Transfer of the
vanA
Resistance Gene from an
Enterococcus faecium
Isolate of Animal Origin to an
E. faecium
Isolate of Human Origin in the Intestines of Human Volunteers
Authors: Lester Camilla H. , Frimodt-Møller Niels , Sørensen Thomas Lund , Monnet Dominique L. , Hammerum Anette M.
Published: January 2006

Transient colonization by vancomycin-resistant enterococci of animal origin has been documented in the intestines of humans. However, little is known about whether transfer of the
vanA
gene occurs in the human intestine. Six volunteers ingested a vancomycin-resistant
Enterococcus faecium
isolate of chicken origin, together with a vancomycin-susceptible
E. faecium
recipient of human origin. Transconjugants were recovered in three of six volunteers. In one volunteer, not only was vancomycin resistance transferred, but also quinupristin-dalfopristin resistance. This study shows that transfer of the
vanA
gene from an
E. faecium
isolate of animal origin to an
E. faecium
isolate of human origin can occur in the intestines of humans. It suggests that transient intestinal colonization by enterococci carrying mobile elements with resistance genes represents a risk for spread of resistance genes to other enterococci that are part of the human indigenous flora, which can be responsible for infections in certain groups of patients, e.g., immunocompromised patients.
Occurrence of OXA-58-Like Carbapenemases in
Acinetobacter
spp. Collected over 10 Years in Three Continents
Authors: Coelho Juliana , Woodford Neil , Afzal-Shah Mariya , Livermore David
Published: January 2006

OXA-58 is a recently described carbapenemase from
Acinetobacter
spp. in Europe. We examined earlier worldwide
Acinetobacter
collections and found
bla
OXA-58
in 30 carbapenem-nonsusceptible isolates, including several isolates collected in Argentina and Kuwait in 1995 and 1996 and in a British outbreak strain from 2000. Most isolates (28 of 30) also had
bla
OXA-51.
We conclude that
bla
OXA-58
is geographically widespread and has occurred in
Acinetobacter
spp. for over 10 years.
Efficacy of Telavancin against Penicillin-Resistant Pneumococci and
Staphylococcus aureus
in a Rabbit Meningitis Model and Determination of Kinetic Parameters
Authors: Stucki Armin , Gerber Peter , Acosta Fernando , Cottagnoud Marianne , Cottagnoud Philippe
Published: January 2006

The penetration of telavancin was 2% into inflamed meninges and ca. 1‰ into noninflamed meninges after two intravenous injections (30 mg/kg of body weight). In experimental meningitis, telavancin was significantly superior to vancomycin combined with ceftriaxone against a penicillin-resistant pneumococcal strain. Against a methicillin-sensitive staphylococcal strain, telavancin was slightly but not significantly superior to vancomycin.
Emergence of
Enterobacteriaceae
Isolates Producing CTX-M Extended-Spectrum β-Lactamase in Austria
Authors: Eisner Alexandra , Fagan Elizabeth J. , Feierl Gebhard , Kessler Harald H. , Marth Egon , Livermore David M. , Woodford Neil
Published: January 2006

Among 149 extended-spectrum β-lactamase (ESBL)-producing
Enterobacteriaceae
isolates collected from patients in southeast Austria from 1998 to 2004, 38
Escherichia coli
isolates and 11
Klebsiella
spp. were CTX-M producers. The proportion of CTX-M-producers among all ESBL producers rose from 0% in 1998 to 58% in 2004. In general, CTX-M-producers had heterogeneous pulsed-field gel electrophoresis patterns, but one
E. coli
isolate was identical to a United Kingdom epidemic CTX-M-15-producing strain, although no epidemiological link with the United Kingdom was apparent.
In Vitro Activity of Doripenem against
Pseudomonas aeruginosa
and
Burkholderia cepacia
Isolates from both Cystic Fibrosis and Non-Cystic Fibrosis Patients
Authors: Traczewski M. M. , Brown S. D.
Published: January 2006

The in vitro activities of doripenem, imipenem, levofloxacin, piperacillin, ceftazidime, aztreonam, tobramycin, and cefepime were determined for 160 isolates of
Pseudomonas aeruginosa
(82 from cystic fibrosis [CF] patients) and 34 isolates of
Burkholderia cepacia
. Doripenem MIC
90
s were lower than those of all other comparative agents against all isolates combined and against all
P. aeruginosa
isolates. Doripenem was as active as levofloxacin and 2- to 32-fold more active than the other comparative agents against
B. cepacia
.
Industry sponsored anti-smoking ads and adolescent reactance: test of a boomerang effect
Authors: Henriksen L , Dauphinee A L , Wang Y , Fortmann S P
Published: January 2006

Objective:To examine whether adolescents’ exposure to youth smoking prevention ads sponsored by tobacco companies promotes intentions to smoke, curiosity about smoking, and positive attitudes toward the tobacco industry.

Design:A randomised controlled experiment compared adolescents’ responses to five smoking prevention ads sponsored by a tobacco company (Philip Morris or Lorillard), or to five smoking prevention ads sponsored by a non-profit organisation (the American Legacy Foundation), or to five ads about preventing drunk driving.

Setting:A large public high school in California’s central valley.

Subjects:A convenience sample of 9th and 10th graders (n  =  832) ages 14–17 years.

Main outcome measures:Perceptions of ad effectiveness, intention to smoke, and attitudes toward tobacco companies measured immediately after exposure.

Results:As predicted, adolescents rated Philip Morris and Lorillard ads less favourably than the other youth smoking prevention ads. Adolescents’ intention to smoke did not differ as a function of ad exposure. However, exposure to Philip Morris and Lorillard ads engendered more favourable attitudes toward tobacco companies.

Conclusions:This study demonstrates that industry sponsored anti-smoking ads do more to promote corporate image than to prevent youth smoking. By cultivating public opinion that is more sympathetic toward tobacco companies, the effect of such advertising is likely to be more harmful than helpful to youth.
Are comprehensive environmental changes as effective as health education for smoking cessation?
Authors: Kadowaki T , Kanda H , Watanabe M , Okayama A , Miyamatsu N , Okamura T , Hayakawa T , Hishida K , Kita Y , Ueshima H
Published: January 2006

Objectives:To compare the effectiveness of health education on smoking cessation for all smokers regardless of their willingness to quit smoking and cumulative environmental changes including designation of smoking places, legislation, and price rise.

Design:Comparison of smoking cessation rates over two time periods: the period of health education on smoking cessation (1997–1999), and the period of cumulative environmental changes (2002–2004).

Setting:An occupational setting in a radiator manufacturing factory in Japan.

Subjects:All habitual male smokers who remained in the worksite through the pertinent time period (n  =  202 in the period of health education and n  =  170 in the period of environmental changes).

Main outcome measurements:Smoking cessation rates at the end of each time period.

Results:The smoking cessation rates over the periods of health education and environmental changes were 8.9% and 7.1%, respectively. There was no difference between these two proportions in a χ2test (p  =  0.513). The age adjustment did not significantly alter the cessation rate.

Conclusions:Cumulative environmental changes are fairly effective in promoting smoking cessation, and may yield similar smoking cessation rates as a health education intervention reaching all smokers regardless of their willingness to quit smoking.
OPTICAL SPECTRA OF SOME PATHOLOGICAL CONDITIONS OF STOMACH TISSUES
Authors: GIRAEV K. M. , ASHURBEKOV N. A. , KOBSEV O. V.
Published: January 2006

Diffuse reflection spectra, diffuse and collimated transmittance spectra of the mucous tissue of stomach anthrus in norm and at a low-differential form of stomach cancer are measured in 300–800 nm spectrum range. The optical coefficients of absorption (μa), scattering (μs) and anisotropy factor (g) for tissues with pathological changes have been calculated by the three-flux model and diffusion approximation methods. It has been determined that the magnitude of optical parameters grows with the development of malignant processes in stomach tissues which indicates the prevalence of forward light scattering and the increase in Mi scatter contribution to the total scattering coefficient of malignant tissues. It has also been shown that the application of two independent theories as methods of tissues' optical parameters determination (μa,μs,g) gives satisfactorily similar results.
A CASE STUDY OF SME–UNIVERSITY RESEARCH COLLABORATION IN THE CONTEXT OF A SMALL PERIPHERAL COUNTRY (CYPRUS)
Authors: HADJIMANOLIS ATHANASIOS
Published: January 2006

The issue of the cooperation of private industrial firms with universities and the relevant transfer of knowledge is discussed here with special reference to the problems and opportunities that small and medium size enterprises face in such cases. A typology of barriers and facilitators within a broad network framework provides a structural approach to the description of these problems and opportunities. The longitudinal investigation of a case study enables an in-depth consideration of the evolution of barriers and facilitators of collaboration over time. The case indicates a fluid pattern of knowledge generation, transmission and absorption, which is then compared to (and contrasted with) the findings of the existing literature.
Indoxyl sulfate induces complex redox alterations in mesangial cells
Authors: Gelasco Andrew K. , Raymond John R.
Published: January 2006

Indoxyl sulfate is a protein metabolite that is concentrated in the serum of patients with chronic renal insufficiency. It also is a uremic toxin that has been implicated in the progression of chronic renal disease in rodent models. We have shown previously that mesangial cell redox status is related to activation of mitogen-activated protein kinases and cell proliferation, which are factors related to glomerular damage. We used three methods to examine the ability of indoxyl sulfate to alter mesangial cell redox as a possible mechanism for its toxicity. Indoxyl sulfate increases mesangial cell reduction rate in a concentration-dependent manner as demonstrated by redox microphysiometry. Alterations occurred at concentrations as low as 100 μM, with more marked alterations occurring at higher concentrations associated with human renal failure. We demonstrated that indoxyl sulfate induces the production of intracellular reactive oxygen species (ROS) in mesangial cells (EC50 = 550 μM) by using the ROS-sensitive fluorescent dye CM-DCF. ROS generation was only partially (∼50%) inhibited by the NADPH oxidase inhibitor diphenylene iodinium at low (≤300 μM) indoxyl sulfate concentrations. Diphenylene iodinium was without effect at higher concentrations of indoxyl sulfate. We also used electron paramagnetic spin resonance spectroscopy with extracellular and intracellular spin traps to show that indoxyl sulfate increases extracellular SOD-sensitive O2−· production and intracellular hydroxyl radical production that may derive from an initial O2−· burst. These results document that indoxyl sulfate, when applied to renal mesangial cells at pathological concentrations, induces rapid and complex changes in mesangial cell redox.
Inhibition of Ras/ERK1/2 signaling protects against postischemic renal injury
Authors: Sabbatini Massimo , Santillo Mariarosaria , Pisani Antonio , Paternò Roberto , Uccello Francesco , Serù Rosalba , Matrone Gianfranco , Spagnuolo Gianrico , Andreucci Michele , Serio Vittorio , Esposito Pasquale , Cianciaruso Bruno , Fuiano Giorgio , Avvedimento Enrico V.
Published: January 2006

The small GTPase p21 Ras and its downstream effectors play a central role in the control of cell survival and apoptosis. We studied the effects of Ras/ERK1/2 signaling inhibition on oxidative damage in cultured renal and endothelial cells and on renal ischemia-reperfusion injury in the rat. Primary human renal tubular and human endothelial ECV304 cells underwent significant cell death when subjected to oxidative stress. This type of stress induced robustly ERK1/2 and phosphoinositide 3-kinase (PI3-kinase) signaling. Inhibition of Ras/ERK1/2 with a farnesyl transferase inhibitor, chaetomellic acid A (S-FTI), or with PD-98059, an inhibitor of MEK, a kinase upstream ERK1/2, significantly reduced the fraction of dead cells. The inhibitor of the PI3-kinase/Akt pathway, LY-294002, failed to exert a protective effect. We have translated these data in a rat model of renal ischemic injury in vivo. In uninephrectomized animals, anesthetized with pentobarbital sodium (Nembutal, 50 mg/kg ip), 24 h after an acute ischemic renal insult (45-min occlusion of left renal artery) a significant fraction of kidney cells succumbed to cell death resulting in renal failure [glomerular filtration rate (GFR) 0.17 ± 0.1 vs. 0.90 ± 0.4 ml·min−1·100 g body wt−1in normal rats]. Rats treated with S-FTI maintained the renal function (GFR 0.50 ± 0.1 ml·min−1·100 g body wt−1), and the kidneys showed a significant reduction of tubular necrosis. Reduction of ischemic damage in kidney and tubular cells paralleled Ha-Ras inhibition, assayed by cytosolic translocation of the protein. These data demonstrate that inhibition of farnesylation and consequently of Ras/ERK1/2 signaling significantly reduces acute postischemic renal injury.
Changes in subcellular distribution of the ammonia transporter, Rhcg, in response to chronic metabolic acidosis
Authors: Seshadri Ramanathan M. , Klein Janet D. , Smith Tekla , Sands Jeff M. , Handlogten Mary E. , Verlander Jill W. , Weiner I. David
Published: January 2006

The primary mechanism by which the kidneys mediate net acid excretion is through ammonia metabolism. In the current study, we examined whether chronic metabolic acidosis, which increases ammonia metabolism, alters the cell-specific and/or the subcellular expression of the ammonia transporter family member, Rhcg, in the outer medullary collecting duct in the inner stripe (OMCDi). Chronic metabolic acidosis was induced in normal SD rats by HCl ingestion for 7 days; controls were pair-fed. The subcellular distribution of Rhcg was determined using immunogold electron microscopy and morphometric analyses. In intercalated cells, acidosis increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the apical plasma membrane. Intracellular Rhcg decreased significantly, and basolateral Rhcg was unchanged. Because apical plasma membrane length increased in parallel with apical Rhcg immunolabel, apical plasma membrane Rhcg density was unchanged. In principal cells, acidosis increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the apical plasma membrane while decreasing the intracellular proportion. In contrast to the intercalated cell, chronic metabolic acidosis did not significantly alter apical boundary length; accordingly, apical plasma membrane Rhcg density increased. In addition, basolateral Rhcg immunolabel increased in response to chronic metabolic acidosis. These results indicate that in the rat OMCDi 1) chronic metabolic acidosis increases apical plasma membrane Rhcg in both the intercalated cell and principal cell where it may contribute to enhanced apical ammonia secretion; 2) increased apical plasma membrane Rhcg results from both increased total protein and changes in the subcellular distribution of Rhcg; 3) the mechanism of Rhcg subcellular redistribution differs in intercalated and principal cells; and 4) Rhcg may contribute to regulated basolateral ammonia transport in the principal cell.
Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion
Authors: Yang Baoxue , Zhao Dan , Qian Liman , Verkman A. S.
Published: January 2006

Transgenic mouse models of defective urinary concentrating ability produced by deletion of various membrane transport or receptor proteins, including aquaporin-2 (AQP2), are associated with neonatal mortality from polyuria. Here, we report an inducible mouse model of AQP2 gene deletion with severe polyuria in adult mice. LoxP sequences were inserted into introns 1 and 2 in the mouse AQP2 gene by homologous recombination in embryonic stem cells. Mating of germ-line AQP2-loxP mice with tamoxifen-inducible Cre-expressing mice produced offspring with inducible homozygous Cre-AQP2-loxP, which had a normal phenotype. Tamoxifen injections over 10 days resulted in AQP2 gene excision, with undetectable full-length AQP2 transcript in kidney and a >95% reduction in immunoreactive AQP2 protein. Urine osmolality decreased from ∼2,000 to <500 mosmol/kgH2O after 4–5 days, with urine output increasing from 2 to 25 ml/day. Urine osmolality did not increase after water deprivation. Interestingly, AQP3 protein expression in the collecting duct was increased by about fivefold after AQP2 gene excision. Mild renal damage was seen after 6 wk of polyuria, with collecting duct dilatation, yet normal creatinine clearance and serum chemistries. These results establish the first adult model of nephrogenic diabetes insipidus (NDI) caused by AQP2 deficiency, with daily urine output comparable to body weight, although remarkable preservation of renal function compared with non-inducible NDI models.
Physiological and Anatomical Properties of Mouse Medial Vestibular Nucleus Neurons Projecting to the Oculomotor Nucleus
Authors: Sekirnjak Chris , du Lac Sascha
Published: January 2006

Neurons in the medial vestibular nucleus (MVN) vary in their projection patterns, responses to head movement, and intrinsic firing properties. To establish whether neurons that participate in the vestibulo-ocular reflex (VOR) have distinct intrinsic physiological properties, oculomotor nucleus (OMN)–projecting neurons were identified in mouse brainstem slices by fluorescent retrograde labeling from the oculomotor complex and targeted for patch-clamp recordings. Such neurons were located in the magnocellular portion of the MVN contralateral to tracer injection, were mostly multipolar, and had soma diameters of around 20 μm. They fired spontaneous action potentials at rates higher than those of other MVN neurons and their spikes were of unusually short duration. OMN-projecting neurons responded to 1-s intracellular current injection with exceptionally high firing rates of >500 spikes/s. Their current–firing relationship was highly linear, with weak firing response adaptation during steady depolarization and little postinhibitory rebound firing after membrane hyperpolarization. Their firing responses were approximately in phase with sinusoidal current injection. The response dynamics of OMN-projecting neurons could be simulated with a simple integrate-and-fire model modified with the addition of small adaptation and rebound conductances. These findings indicate that the membrane properties of OMN-projecting neurons allow them to respond to head movements reliably and with high sensitivity but without substantially altering input dynamics.
The Apostolic Fathers: The Didache
Authors: Draper Jonathan A.
Published: January 2006

The Didache is perhaps the earliest test in the collection of writings known as the Apostolic Fathers. It purports to be a collection of instructions given by Jesus, through the twelve apostles, to provide catechesis for new Gentile converts prior to|baptism. The text is particularly important in providing insight into the life of an early Jewish Christian community, including its baptismal and Eucharistic liturgy, as well as offering evidence for the evolution of leadership structures in at least one early Christian community.
Introduction to Special Issue
Authors: Gathercole Virginia C. Mueller
Published: January 2006

This special issue focuses on evidence bearing on the specific ways in which linguistic differences across languages may affect what is learned early (or late) in language and to what extent language-specific structures interact with cognition. The ultimate question is whether or not development follows a universal course or is influenced by the linguistic system being acquired. Of particular interest in the linguistic realm are data exploring what governs the late development of linguistic forms; of particular interest in the cognitive realm are areas for which crosslinguistic data reveal linguistic influences on the timing of development of cognitive concepts or on attentional patterns in children. The combined research suggests that the morphosyntactic structure of the language, the semantic notions encoded in the language and the cognitive underpinnings related to those structures all play a role in the course of development.
The influence of typology and modality on the acquisition of verb agreement morphology in British Sign Language
Authors: Morgan Gary , Barrière Isabelle , Woll Bencie
Published: January 2006

The development of morphological verb agreement in childrenís language involves several different linguistic phenomena. Languageñspecific influences impact on developmental patterns and age of acquisition. This study addresses three potential factors involved in the development of verb agreement morphology in sign languages and more specifically in a case study of one deaf child of native signing parents acquiring British Sign Language. The data were collected longitudinally between the ages of 1;10 and 3;0 with analysis concentrating on the emergence and mastery of the inflectional system for encoding person agreement. The data are compared with other studies of verb agreement in both signed and spoken language acquisition. Analysis reveals a relatively late onset of verb use and protracted development of the agreement system with productive use of inflectional morphology reached at 3;0. The observed developmental patterns and age of acquisition are explained by the combined influence of a set of both typological and modality-specific factors.
Consciousness, self-consciousness, and the modern self
Authors: Brinkmann Klaus
Published: January 2006

The concept of the self is embedded in a web of relationships of other concepts and phenomena such as consciousness, self-consciousness, personal identity and the mind–body problem. The article follows the ontological and epistemological roles of the concept of selfconsciousness and the structural co-implication of consciousness and self-consciousness from Descartes and Locke to Kant and Sartre while delineating its subject matter from related inquiries into the relationship between the mind and the body, personal identity, and the question whether consciousness is an irreducible reality sui generis or essentially a neurobiological entity. Over the course of its history, the modern self turns out to become an ever more elusive phenomenon, while its roles as a bearer of individual responsibility and as a subject of reflective endorsement of the truth become ever more pronounced.
The reflexivity of cognitive science: the scientist as model of human nature
Authors: Cohen-Cole Jamie
Published: January 2006

This article examines how experimental psychology experienced a revolution as cognitive science replaced behaviorism in the mid-20th century. This transition in the scientific account of human nature involved making normal what had once been normative: borrowing ideas of democratic thinking from political culture and conceptions of good thinking from philosophy of science to describe humans as active, creatively thinking beings, rather than as organisms that simply respond to environmental conditions. Reflexive social and intellectual practices were central to this process as cognitive scientists used anti-positivist philosophy of science simultaneously to justify their own work as valid and also as a model of human thinking. In the process, the normative philosophy of science or ‘good academic thinking’ that cognitive scientists used to reshape the discipline of psychology and characterize themselves became, at the same time, the descriptive model of human nature.
The Protestant Ethic thesis: Weber’s missing psychology
Authors: Mather Ronald
Published: January 2006

Commentators on Weber’s The Protestant Ethic and the Spirit of Capitalism have tended to view that work within the context of world-historical social processes and change. Recently, more literary forms of analyses have come to the fore emphasizing Weber’s indebtedness to the philosophical/literary efforts of Nietzsche and Goethe, among others. The following offers the preliminary observation that the concept of ‘drive’ understood as a mode of psychological operation and process considerably complicates any possible interpretation of the essay itself. Weber’s refusal to specify the exact nature and extent of the psychological Antriebe underlying his rational actor may make a decisive interpretation of the text impossible. Nevertheless, there may be good reason for supposing that Weber’s usage of the terms ‘drive’ and ‘maxim’ is indicative of a Fichtean synthesis of anthropological impulses and the operations of the rational intellect via his reading of Hugo Münsterberg.
The way of the social: from Durkheim’s society to a postmodern sociality
Authors: Gafijczuk Dariusz
Published: January 2006

This article investigates the meaning of the ‘social’ based on Durkheim’s philosophy of society as a ‘collective representation’. I argue that the social, the way Durkheim formulates it, is an abstract sign for reality, a metaphor, which operates on the level of language. Because of this fact, the ‘social’ is from the start limited in its functionality as a descriptor, but it also contains within its own linguistic form, in its word, the possibility of renewal and renaming that is the unique force inherent in language. I propose that this origin of the social operates according to the ‘spirit of postmodernism’, which constitutes a common response to modernity, by what later differentiates itself into the currents of sociology and postmodernism.
Supporting information technology across health boards in New Zealand: themes emerging from the development of a shared services organization
Authors: Day K. J. , Norris A. C.
Published: January 2006

Shared services organizations are ascribed with adding value to business in several ways but especially by sharing resources and leading to economies of scale. However, these gains are not automatic and in some instances, particularly healthcare, they are difficult to achieve. This article describes a project to develop a shared services information technology infrastructure across two district health boards in New Zealand. The study reveals valuable insight into the crisis issues that accompany change management and identifies emergent themes that can be used to reduce negative impact.
Quality labelling of medical web content
Authors: Mayer Miquel Angel , Karkaletsis Vangelis , Archer Phil , Ruiz Pau , Stamatakis Konstantinos , Leis Angela
Published: January 2006

As the number of medical websites in various languages increases, it is increasingly necessary to establish specific criteria and control measures that give consumers some guarantee that the health websites they are visiting meet a minimum level of quality standards. Further, reassurance is needed that the professionals offering the information are suitably qualified. The paper briefly presents the current mechanisms for labelling medical web content and introduces the work done in the EC-funded project Quatro. This has defined a vocabulary for quality labels and a schema to deliver them in a machine-processable format. In addition, the paper proposes the development of a labelling platform that will assist the work of medical labelling agencies in automating, up to a certain level, the retrieval of unlabelled medical websites and their labelling, and the monitoring of labelled websites as to whether they are still satisfying the criteria.
Art, crafts and Paleolithic art
Authors: Abadía Oscar Moro
Published: January 2006

This article initially examines the foundations of our modern understanding of Paleolithic art. Taking the period 1860-1905 into account, I show that the depiction of Paleolithic art elaborated by Western archaeologists at that time was largely based on the projection of categories used to characterize craft at the end of the nineteenth century with prehistoric art. As I depict in the final section of the article, the weakening of evolutionism and the recognition of the complexity of primitive societies at the turn of the century provoked a new definition of Paleolithic art, which included cave paintings.
Yahweh and His Clio: Critical Theory and the Historical Criticism of the Hebrew Bible
Authors: Miller R. D.
Published: January 2006

Discussion about the reconstruction of the history of ancient Israel seldom interacts with theoretical literature on the nature of history. Modern attempts to write Israel’s history, however, have been shaped by their theoretical underpinnings for the past two centuries. This essay explores the epistemological underpinnings of the historical criticism of the Hebrew Bible, outlines trends in historiographical theory, and assesses the impact newer theories of intellectual cultural history can have on studies of the history of the social world of ancient Israel.
Ark-Eology: Shifting Emphases in ‘Ark Narrative’ Scholarship
Authors: Bodner Keith
Published: January 2006

A central character in 1 Samuel 4-6 is the Ark of the Covenant. The Ark is captured in battle, and subsequently wreaks havoc throughout the land of the Philistines until its subsequent return to the borders of Israel. Commonly referred to as the ‘Ark Narrative’ in scholarly literature, 1 Samuel 4-6 has often been viewed as a separate unit within the larger Deuteronomistic History. Although the Ark Narrative has been the subject of considerable scholarly interest, the methodological foci of such studies appear to have undergone a shift in more recent times. While earlier studies espoused a host of different critical approaches, such as tradition-historical, form-critical and redactional methodologies, it would seem that more recent studies have exhibited greater interest in literary appraisal and narrative criticism. This article presents a summary of recent research on the Ark Narrative of 1 Samuel 4-6 by 12 scholars: Robert Gordon, Lyle Eslinger, Peter Miscall, Walter Brueggemann, Yehoshua Gitay, Robert Polzin, J.P. Fokkelman, Bruce Birch, E.M.M. Eynikel, Graeme Auld, Barbara Green and Antony F. Campbell, SJ.
Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis
Authors: Schulze Harald , Korpal Manav , Hurov Jonathan , Kim Sang-We , Zhang Jinghang , Cantley Lewis C. , Graf Thomas , Shivdasani Ramesh A.
Published: January 2006

To produce blood platelets, megakaryocytes elaborate proplatelets, accompanied by expansion of membrane surface area and dramatic cytoskeletal rearrangements. The invaginated demarcation membrane system (DMS), a hallmark of mature cells, has been proposed as the source of proplatelet membranes. By direct visualization of labeled DMS, we demonstrate that this is indeed the case. Late in megakaryocyte ontogeny, the DMS gets loaded with PI-4,5-P2, a phospholipid that is confined to plasma membranes in other cells. Appearance of PI-4,5-P2 in the DMS occurs in proximity to PI-5-P-4-kinase α (PIP4Kα), and short hairpin (sh) RNA-mediated loss of PIP4Kα impairs both DMS development and expansion of megakaryocyte size. Thus, PI-4,5-P2 is a marker and possibly essential component of internal membranes. PI-4,5-P2 is known to promote actin polymerization by activating Rho-like GTPases and Wiskott-Aldrich syndrome (WASp) family proteins. Indeed, PI-4,5-P2 in the megakaryocyte DMS associates with filamentous actin. Expression of a dominant-negative N-WASp fragment or pharmacologic inhibition of actin polymerization causes similar arrests in proplatelet formation, acting at a step beyond expansion of the DMS and cell mass. These observations collectively suggest a signaling pathway wherein PI-4,5-P2 might facilitate DMS development and local assembly of actin fibers in preparation for platelet biogenesis.
Detection and properties of the human proliferative monocyte subpopulation
Authors: Clanchy Felix I L , Holloway Alice C , Lari Roya , Cameron Paul U , Hamilton John A
Published: January 2006

Peripheral blood monocyte subpopulations have been reported and can give rise to diverse, differentiated phenotypes. A subpopulation(s) of human monocytes can proliferate in vitro in response to macrophage-colony stimulating factor (M-CSF; or CSF-1). This population, termed the proliferative monocyte (PM), is presumably less mature than other monocytes; however, it has not been defined further. Previous studies monitoring the frequency of the slowly cycling PM from different donors indicated that the assay for their reproducible measurement required improvement. We demonstrate that for optimal PM detection, high 5-bromo-2′-deoxyuridine concentrations are required over a delayed and wide time-frame. Surface marker phenotyping by flow cytometry showed that freshly isolated PM are CD14+ and could be distinguished from two other human monocyte subpopulations, namely, the CD14loCD16+ and CD14loCD64– subsets. PM express relatively high levels of CD64 and CD33 but have relatively low CD13 expression; they are also c-Fms+ and human leukocyte antigen-DR+. Labeling with carboxyfluorescein diacetate succinimidyl ester (CFSE) enabled the estimation of the number of PM divisions over time. Following CFSE labeling and culture, PM were sorted from the nonproliferating population and shown to have a distinctive, spindle-shaped morphology and higher capacity to form multinucleated, tartrate-resistant acid phosphatase+ cells in the presence of M-CSF and receptor activator of nuclear factor-κB ligand. The phenotype and properties of the PM subpopulation were examined as a prelude to determining its role in disease using methods that can be applied to clarify human monocyte heterogeneity.
Smooth muscle of the dorsal aorta shares a common clonal origin with skeletal muscle of the myotome
Authors: Esner Milan , Meilhac Sigolène M. , Relaix Frédéric , Nicolas Jean-François , Cossu Giulio , Buckingham Margaret E.
Published: January 2006

We show that cells of the dorsal aorta, an early blood vessel, and of the myotome, the first skeletal muscle to form within the somite, derive from a common progenitor in the mouse embryo. This conclusion is based on a retrospective clonal analysis, using a nlaacZ reporter targeted to the α-cardiac actin gene. A rare intragenic recombination event results in a functional nlacZ sequence, giving rise to clones ofβ-galactosidase-positive cells. Periendothelial and vascular smooth muscle cells of the dorsal aorta are the main cell types labelled,demonstrating that these are clonally related to the paraxial mesoderm-derived cells of skeletal muscle. Rare endothelial cells are also seen in some clones. In younger clones, arising from a recent recombination event, myotomal labelling is predominantly in the hypaxial somite, adjacent to labelled smooth muscle cells in the aorta. Analysis of Pax3GFP/+ embryos shows that these cells are Pax3 negative but GFP positive, with fluorescent cells in the intervening region between the aorta and the somite. This is consistent with the direct migration of smooth muscle precursor cells that had expressed Pax3. These results are discussed in terms of the paraxial mesoderm contribution to the aorta and of the mesoangioblast stem cells that derive from it.
Epidemiology of Vancomycin-Induced Neutropenia In Patients Receiving Home Intravenous Infusion Therapy
Authors: Pai Manjunath P , Mercier Renee-Claude , Koster Sarah A
Published: January 2006

Background:

Vancomycin is frequently used to manage serious resistant gram-positive Infections. Neutropenia, whose epidemiology has not been well characterized, is a potentially serious adverse event associated with the use of vancomycin.

Objective:

To characterize the incidence and risk factors for development of vancomycin-induced neutropenia in patients treated with home intravenous vancomycin therapy.

Methods:

A retrospective chart review was conducted of adult patients receiving vancomycin therapy through the University of New Mexico Home Intravenous Infusion Clinic between January 1998 and December 2004. Data collection included demographics, comorbid conditions, dose and duration of vancomycin therapy, indications for vancomycin use, vancomycin concentrations, all concurrent medications, laboratory data, culture and susceptibility data, reasons for antibiotic alteration or discontinuations, all other recorded adverse events, management of adverse events, and outcomes of adverse events.

Results:

A total of 372 charts of patients managed through the clinic were reviewed and 114 patients treated with vancomycin were identified. Fourteen (12%) cases of vancomycin-induced neutropenia were identified; 4 (3.5%) cases included a reduction in absolute neutrophil count to 500 cells/mm3 or less. The mean ± SD duration of vancomycin therapy and time to neutropenia were 32 ± 29 and 26 ± 15 days, respectively. Laboratory monitoring was performed on a weekly basis and resolution of vancomycin-induced neutropenia occurred promptly after discontinuation. Total vancomycin doses used and serum concentrations were not associated with the development of neutropenia.

Conclusions:

Vancomycin-induced neutropenia may occur at a higher frequency than previously reported. Clinicians should monitor hematologic parameters at least weekly in patients receiving home intravenous vancomycin therapy.
Allocentric Spatial Referencing of Neuronal Activity in Macaque Posterior Cingulate Cortex
Authors: Dean Heather L. , Platt Michael L.
Published: January 2006

Neuronal activity in posterior cingulate cortex (CGp) is modulated by visual stimulation, saccades, and eye position, suggesting a role for this area in visuospatial transformations. The goal of this study was to determine whether neuronal responses in CGp are anchored to the eyes, head, or outside the body (allocentrically). To discriminate retinocentric from nonretinocentric spatial referencing, the activity of single CGp neurons was recorded while monkeys (Macaca mulatta) performed delayed-saccade trials initiated randomly from three different starting positions to a linear array of targets passing through the neuronal response field. For most neurons, tuning curves, segregated by fixation point, aligned more closely when plotted with respect to the display than when plotted with respect to the eye, suggesting a nonretinocentric frame of reference. A second experiment differentiated between spatial referencing in coordinates anchored to the head or body and allocentric spatial referencing. Monkeys shifted gaze from a central fixation point to the array of previously used targets both before and after whole-body rotation with respect to the display. For most neurons, tuning curves, segregated by fixation position, aligned more closely when plotted as a function of target position in the room than when plotted as a function of target position with respect to the monkey. These data indicate that a population of CGp neurons encodes visuospatial events in allocentric coordinates.
Spontaneous Pain, Both Neuropathic and Inflammatory, Is Related to Frequency of Spontaneous Firing in Intact C-Fiber Nociceptors
Authors: Djouhri Laiche , Koutsikou Stella , Fang Xin , McMullan Simon , Lawson Sally N.
Published: January 2006

Spontaneous pain, a poorly understood aspect of human neuropathic pain, is indicated in animals by spontaneous foot lifting (SFL). To determine whether SFL is caused by spontaneous firing in nociceptive neurons, we studied the following groups of rats: (1) untreated; (2) spinal nerve axotomy (SNA), L5 SNA 1 week earlier; (3) mSNA (modified SNA), SNA plus loose ligation of the adjacent L4 spinal nerve with inflammation-inducing chromic gut; and (4) CFA (complete Freund’s adjuvant), intradermal complete Freund’s adjuvant-induced hindlimb inflammation 1 and 4 d earlier. In all groups, recordings of SFL and of spontaneous activity (SA) in ipsilateral dorsal root ganglion (DRG) neurons (intracellularly) were made. Evoked pain behaviors were measured in nerve injury (SNA/mSNA) groups. Percentages of nociceptive-type C-fiber neurons (C-nociceptors) with SA increased in intact L4 but not axotomized L5 DRGs in SNA and mSNA (to 35%), and in L4/L5 DRGs 1–4 d after CFA (to 38–25%). SFL occurred in mSNA but not SNA rats. It was not correlated with mechanical allodynia, extent of L4 fiber damage [ATF3 (activation transcription factor 3) immunostaining], or percentage of L4 C-nociceptors with SA. However, L4 C-nociceptors with SA fired faster after mSNA (1.8 Hz) than SNA (0.02 Hz); estimated L4 total firing rates were ∼5.0 and ∼0.6 kHz, respectively. Similarly, after CFA, faster L4 C-nociceptor SA after 1 d was associated with SFL, whereas slower SA after 4 d was not. Thus, inflammation causes L4 C-nociceptor SA and SFL. Overall, SFL was related to SA rate in intact C-nociceptors. Both L5 degeneration and chromic gut cause inflammation. Therefore, both SA and SFL/spontaneous pain after nerve injury (mSNA) may result from cumulative neuroinflammation.
Rapid Brain Discrimination of Sounds of Objects
Authors: Murray Micah M. , Camen Christian , Gonzalez Andino Sara L. , Bovet Pierre , Clarke Stephanie
Published: January 2006

Electrical neuroimaging in humans identified the speed and spatiotemporal brain mechanism whereby sounds of living and man-made objects are discriminated. Subjects performed an “oddball” target detection task, selectively responding to sounds of either living or man-made objects on alternating blocks, which were controlled for in their spectrogram and harmonics-to-noise ratios between categories. Analyses were conducted on 64-channel auditory evoked potentials (AEPs) from nontarget trials. Comparing responses to sounds of living versus man-made objects, these analyses tested for modulations in local AEP waveforms, global response strength, and the topography of the electric field at the scalp. In addition, the local autoregressive average distributed linear inverse solution was applied to periods of observed modulations. Just 70 ms after stimulus onset, a common network of brain regions within the auditory “what” processing stream responded more strongly to sounds of man-made versus living objects, with differential activity within the right temporal and left inferior frontal cortices. Over the 155–257 ms period, the duration of activity of a brain network, including bilateral temporal and premotor cortices, differed between categories of sounds. Responses to sounds of living objects peaked ∼12 ms later and the activity of the brain network active over this period was prolonged relative to that in response to sounds of man-made objects. The earliest task-related effects were observed at ∼100 ms poststimulus onset, placing an upper limit on the speed of cortical auditory object discrimination. These results provide critical temporal constraints on human auditory object recognition and semantic discrimination processes.
Consolidation stress effects on the strength of stabilised Swedish soils
Authors: Åhnberg H.
Published: January 2006

Common estimates of the design strength of soft soils stabilised by deep mixing do not take into account the effect of the confining stresses on the behaviour of the material. This is largely an effect of the limited knowledge of how different consolidation stresses affect the strength of such soils. Furthermore, an increasing variety of binders is used nowadays in deep mixing of soils, and it is uncertain whether these affect the stress dependence in different ways. To gain increased insight into this aspect, a series of triaxial compression tests, unconfined compression tests and oedometer tests has been performed on soils stabilised with cement, lime, cement–lime, cement–slag, cement–fly ash and slag–lime. The results show that both the drained and the undrained strength are dependent on the confining stresses. The extent of this stress dependence is affected by the stress and strength level. The type of binder used affects the achieved strength level to a great extent, but in principle is of less importance for the response of the material. The results provide a set of parameters for rough estimates of the stress dependence for both the undrained and drained strength of stabilised soils. By applying the concept of quasi-preconsolidation pressures, an improved method of modelling the strength of stabilised soils is proposed.

Les évaluations courantes de la résistance nominale des sols tendres stabilisés par mixage profond ne prennent pas en compte l'effet des contraintes de confinement sur le comportement de la matière. Ceci est dû, en grande partie, au niveau de connaissance limité sur les effets de différentes contraintes de consolidation sur la résistance de ces sols. De plus, une variété croissante d'agents liants est utilisée aujourd'hui dans le mixage profond des sols; or, on ne peut déterminer dans quelle mesure ceux-ci affectent le rôle de la contrainte. Pour mieux étudier ce point, une série d'essais de compression triaxiale, d'essais de compression non confinée et d'essais oedométriques a été réalisée dans des sols stabilités au ciment, à la chaux, au ciment-chaux, au ciment-machefer, au ciment-cendre volante et au machefer-chaux. Les résultats montrent que tant la résistance drainée que la résistance non drainée dépendent des contraintes de confinement. L'étendue de cette dépendance est affectée par le niveau de contrainte et de résistance. Le type d'agent liant utilisé affecte dans une grande mesure le niveau de résistance atteint mais en principe, son importance est moindre quant à la réponse de la matière. Les résultats donnent un jeu de paramètres qui servira à des évaluations approximatives de la dépendance vis-à-vis de la contrainte pour la résistance non drainée et la résistance drainée des sols stabilisés. En appliquant le concept de pressions de quasi-préconsolidation, nous proposons une méthode améliorée pour la modélisation de la résistance des sols stabilisés.