bluuebunny/crossref_metadata_2025 huggingface dataset:
Industrial dynamics and managerial networking in an emerging market: the case of China
Authors: Luo Yadong
Published: November 2003

This study examines how industrial conditions influence the level of executives' managerial networking with decision‐makers in other entities such as buyers, suppliers, competitors, distributors, and regulators in an emerging market. Corroborating a view that social capital holds contingent value, we theorize that executives facing different industrial conditions have different levels of commitment to exploiting interpersonal ties for fulfilling organizational needs. We propose that managerial networking is influenced by exogenous industrial attributes such as structural uncertainty, sales growth, regulatory stringency, competitive pressure, and production capacity utilization. Our analysis of executives in 364 firms in China demonstrates that the level of managerial networking increases when uncertainty, regulation, and competition increase and production capacity utilization decreases. For a specific firm, the link between industrial dynamics and managerial networking is moderated by its strategic proactiveness. Copyright © 2003 John Wiley & Sons, Ltd.
Punishing dangerousness through preventive detention: Illustrating the institutional link between school and prison
Authors: Casella Ronnie
Published: November 2003

Evidence‐based observations of how the juvenile justice and educational systems can work together more effectively are presented.
High‐poverty secondary schools and the juvenile justice system: How neither helps the other and how that could change
Authors: Balfanz Robert , Spiridakis Kurt , Neild Ruth Curran , Legters Nettie
Published: November 2003

Evidence‐based observations of how the juvenile justice and educational systems can work more effectively together are presented.
Interaction of intact type VI collagen with hyaluronan
Authors: McDevitt Cahir A. , Marcelino Jose , Tucker Lynne
Published: November 2003

The capacity of non‐pepsinyzed type VI collagen to oind to hyaluronan was investigated. Type VI collagen was extracted from bovine meniscal cartilage with 6 M GuHCl and purified by extraction of PEG precipitates and dissociative Sephacryl S‐500 HR chromatography. Type VI collagen, detected with a monoclonal antibody, bound in 0.5 M NaCl to hyaluronan‐coated micro‐wells, the degree of binding being higher at 37°C than 23°C and 4°C. Incubation of type VI collagen in competitive inhibition assays with testicular hyaluronidase digests of hyaluronan in liquid phase, reduced binding of the protein to hyaluronan‐coated microwells to background levels. Thus, non‐pepsinyzed type VI collagen binds to hyaluronan in vitro.
Structure/function relationships in the inhibition of thimet oligopeptidase by carboxyphenylpropyl‐peptides
Authors: Knight C.Graham , Barrett Alan J.
Published: November 2003

Some novel N‐[1(RS)‐carboxy‐3‐phenylpropyl]tripeptide p‐aminobenzoates have been synthesised as inhibitors of thimet oligopeptidase (EC 3.4.24.15). These compounds are considered to bind as substrate analogues with the Cpp group in S1 and the peptide portion in the S′ sites. The most potent inhibitor is Cpp‐Ala‐Pro‐Phe‐pAb, which has a K
1 = 7 nM. Substitution of Gly for Ala at P1′ leads to weaker binding which can be ascribed to increased rotational freedom. Good substrates often have Pro at P2′ and Pro is favoured over Ala at this position in the inhibitors, too. When P2′ is Pro, Phe is preferred over Tyr and Trp in P3′. The p‐aminobenzoate group makes an important contribution to the binding, probably by forming a salt bridge, and removal of the C‐terminal negative charge results in much less potent inhibitors.
Fragmentation of proteins by S. aureus strain V8 protease
Authors: Sørensen Steen Bech , Sørensen Thomas Lykke , Breddam Klaus
Published: November 2003

Staphylococcus aureus strain V8 protease is a serine endopeptidase which cleaves peptide bonds at the carboxyl side of Glu and Asp. Specific cleavage at Glu has previously been achieved in ammonium bicarbonate whereas in sodium phosphate cleavage at both Glu and Asp was observed. However, it is shown here that bicarbonate does not restrict the specificity to Glu‐X bonds, it simply inhibits the enzyme. The degradation of a mixture of oxidized insulin and glucagon proceeds similarly in the two buffers, although faster in phosphate.
Separation of active and inactive (nonphosphorylating) Ca2+‐ATPase in sacroplasmic reticulum subfractions from low‐frequency‐stimulated rabbit muscle
Authors: Matsushita Shigeki , Dux László , Pette Dirk
Published: November 2003

Chronic low‐frequency stimulation elicits in rabbit fast‐twitch muscle a partial inactivation of the sarcoplasmic reticulum (SR) Ca2+‐ATPase and Ca2+‐uptake activities. Inactive Ca2+‐ATPase was enriched in a light microsomal fraction by sucrose density gradient centrifugation after calcium oxalate loading in the presence of ATP. This fraction showed a reduced specific activity and phosphoprotein formation of the Ca2+‐transport ATPase. These results suggest that the inactivation of the Ca2+‐ATPase as induced by increased contractile activity, is confined to a specific SR vesicle population.
Phosphorylation of recoverin, the calcium‐sensitive activator of photoreceptor guanylyl cyclase
Authors: Lambrecht H.-G. , Koch K.-W.
Published: November 2003

Recoverin, a new calcium binding protein from bovine rod photoreceptor cells, activates guanylyl cyclase below a free calcium concentration of 200 nM. We show here that recoverin is phosphorylated by an endogeneous kinase and Mg‐ATP at the same decreased calcium concentration. The calcium‐dependent activation of guanylyl cyclase is enhanced in the presence of ATP. We suggest that phosphorylation of recoverin reinforces the stimulation of guanylyl cyclase at decreased calcium concentrations.
2‐Deoxy‐2‐fluoro‐D‐galactose protein N‐glycosylation
Authors: Loch Nikolaus , Geilen Christoph C. , Spörndle Irmgard , Oberdorfer Franz , Keppler Dietrich , Tauber Rudolf , Reutter Werner
Published: November 2003

2‐Deoxy‐2‐fluoro‐D‐galactose (dGalF), added to the medium of primary cultured rat hepatocytes, inhibited N‐glycosylation on membrane (gp 120) and secretory glycoproteins (α
1‐macroglobulin) in a concentration dependent manner. Complete inhibition of N‐glycosylation was achieved at concentrations of 1 mM and above. At identical concentrations, 2‐deoxy‐2‐fluoro‐D‐glucose (dGlcF) caused only incomplete inhibition of N‐glycosylation. dGalF reduced incorporation of D‐[2,6‐3H]mannose into lipid‐linked oligosaccharides indicating interference with their assembly in the dolichol cycle.
Ubiquitination of endogenous calmodulin in rabbit tissue extracts
Authors: Laub Markus , Jennissen Herbert P.
Published: November 2003

Previously we were able to show that purified calmodulins from vertebrates, plants (spinach) and the mold Neurospora crassa can be covalently conjugated to ubiquitin in a Ca2+‐dependent manner. It was therefore pertinent to answer the question if a tissue extract contains all the components necessary for the endogenous synthesis of ubiquityl calmodulin (uCaM). Therefore [125I]ubiquitin, ATP/Mg2+ and Ca2+ were added to tissue extracts enriched by a single ion exchange step. In such extracts of red blood cells, skeletel muscle and testis a novel ubiquitin conjugate of 27–29 kDa is formed. This novel band could be identified as ubiquityl‐calmodulin by the following methods: (i) identical R
1‐value of novel conjugate and standard uCaM in SDS‐PAGE; (ii) Ca2+‐dependent conjugate formation; (iii) Ca2+‐dependent adsorption to fluphenazine‐Sepharose; (iv) Ca2+‐dependent mobility change of the novel conjugate during SDS‐PAGE; and (v) inhibition of conjugate band formation by phosphorylate kinase. These experiments clearly demonstrate that ubiquityl calmodulin can be endogenously generated in enriched cellular extracts and strongly indicate that this reaction is of importance in vivo.
The major endogenous bovine brain protein kinase C inhibitor is a heat‐labile protein
Authors: Fraser Elaine D. , Walsh Michael P.
Published: November 2003

A crude cytosolic fraction prepared from bovine brain contained protein kinase C, as shown by immunoblotting, but its activity was undetectable, suggesting the presence of interfering factors. Phosphatase, ATPase and protease activities did not account for the absence of detectable protein kinase C activity. The major contributing factor was found to be a heat‐labile protein which was separated from the kinase by ion‐exchange chromatography. The contribution to the total inhibitory activity of heat‐stable proteins was relatively minor, suggesting that they may not function physiologically as protein kinase C inhibitors.
Oral glucosamine and the management of feline idiopathic cystitis
Authors: Gunn-Moore D.A. , Shenoy C.M.
Published: November 2003

Oral glucosamine was compared to a placebo for the management of cats with feline idiopathic cystitis (FIC) in a randomised, double-blinded, placebo-controlled, study. Forty cats with a history of recurrent cystitis due to FIC were divided into two groups and treated daily per os with either 125 mg N-acetyl glucosamine or a placebo for six months. Owners graded their cats' clinical signs at the beginning and end of the study, and kept daily diaries documenting signs of cystitis using visual analogue scales. Further episodes of cystitis were seen in 26 (65%) of the cats during the study. Affected cats experienced a mean of five recurrences (range 1–19) with each recurrence lasting a mean of four days (range 1–64 days).

There were no significant differences between the two groups when considering the owners assessments of the mean health score ( P > 0.5), the average monthly clinical score ( P = 0.22) or the average number of days with clinical signs ( P = 0.28). Two cats suffered from such severe recurrent urethral obstruction that they were euthanased; they were both in the placebo group. Compared to the start of the study the majority of cats in both groups improved significantly ( P < 0.001) (mean health score of each group at the start was 0.5 ± SD 0.5, compared to glucosamine 4.4 ± 0.7 and placebo 3.9 ± 1.6 at the end). This is believed to have occurred because the owners of 36 of the 40 cats (90%) started feeding more canned cat food. The urine specific gravity at the start of the trial was significantly higher (mean 1.050 ± SD 1.007) than when reassessed one month later (1.036 ± 1.010, P < 0.01).
Inflammatory prompts produce isoform‐specific changes in the expression of leukotriene B4 ω‐hydroxylases in rat liver and kidney
Authors: Kalsotra Auinash , Cui Xiaoming , Antonovic Leposava , Robida Aaron M , Morgan Edward T , Strobel Henry W
Published: November 2003

Cytochrome P450 (CYP) 4Fs metabolize leukotriene B4 and other inflammatory mediators in the arachidonic acid cascade. Here we show that lipopolysaccharide (LPS) treatment suppresses CYP4F4 and up‐regulates CYP4F5 mRNA expression in rat liver whereas renal CYP4Fs are essentially unchanged. BaSO4 treatment, in contrast, increases both hepatic and renal CYP4F expression levels. Thus, distinct regulatory mechanisms in CYP4F expression might operate under different inflammatory prompts. To examine hepatic totipotency, primary hepatocytes were treated with varying doses of LPS resulting in decrease in all the CYP4F isoforms. Treatment of hepatocytes with 5 ng/ml of interleukin‐1β mimics the in vivo effects of LPS on CYP4F expression.
Caenorhabditis elegans dna‐2is involved in DNA repair and is essential for germ‐line development
Authors: Lee Myon Hee , Han Sung Min , Han Ji Won , Kim Yun Mi , Ahnn Joohong , Koo Hyeon-Sook
Published: November 2003

Caenorhabditis elegansgerm cell proliferation and development were severely damaged in second generationdna‐2homozygotes. Even in the first generation, a much higher incidence of aberrant chromosomes in oocytes and resultantly higher embryonic lethality were found vs. wild type, when DNA breaks were induced by γ‐rays or camptothecin. The deficiency ofdna‐2in combination with RNA interference onmre‐11gene expression synergistically aggravated germ‐line development, especially oocyte formation. These results suggest thatC. elegansDna‐2 is involved in a DNA repair pathway paralleling homologous recombination or non‐homologous end joining withmre‐11participation.
D‐Ribose improves diastolic function and quality of life in congestive heart failure patients: a prospective feasibility study
Authors: Omran Heyder , Illien Stefan , MacCarter Dean , St. Cyr John , Lüderitz Berndt
Published: November 2003

Patients with chronic coronary heart disease often suffer from congestive heart failure (CHF) despite multiple drug therapies. D‐Ribose has been shown in animal models to improve cardiac energy metabolism and function following ischaemia. This was a prospective, double blind, randomized, crossover design study, to assess the effect of oral D‐ribose supplementation on cardiac hemodynamics and quality of life in 15 patients with chronic coronary artery disease and CHF. The study consisted of two treatment periods of 3 weeks, during which either oral D‐ribose or placebo was administered followed by a 1‐week wash out period, and then administration of the other supplement. Assessment of myocardial functional parameters by echocardiography, quality of life using the SF‐36 questionnaire and functional capacity using cycle ergometer testing was performed. The administration of D‐ribose resulted in an enhancement of atrial contribution to left ventricular filling (40±11 vs. 45±9%, P=0.02), a smaller left atrial dimension (54±20 vs. 47±18 ml, P=0.02) and a shortened E wave deceleration (235±64 vs. 196±42, P=0.002) by echocardiography. Further, D‐ribose also demonstrated a significant improvement of the patient's quality of life (417±118 vs. 467±128, P≤0.01). In comparison, placebo did not result in any significant echocardiographic changes or in quality of life. This feasibility study in patients with coronary artery disease in CHF revealed the beneficial effects of D‐ribose by improving diastolic functional parameters and enhancing quality of life.
Reference ranges for natriuretic peptides for diagnostic use are dependent on age, gender and heart rate
Authors: Loke Ian , Squire Iain B. , Davies Joan E. , Ng Leong L.
Published: November 2003

Background:

Plasma natriuretic peptide levels may be useful in the diagnosis of heart failure. The available natriuretic peptide assays differ markedly in their performance characteristics. In addition, plasma levels are influenced by a number of factors including age and gender.

Aims:

The aim of this study was to describe, in a healthy population, the influence of clinical and echocardiographic parameters on three natriuretic peptide moieties.

Methods:

1360 individuals were screened for the presence of left ventricular systolic dysfunction. We identified a cohort (n=720) of men aged 45–80 years (n=417) and women aged 55–80 years (n=303). None had history of cardiovascular disease or were taking any cardiovascular medication. All had normal echocardiographic and ECG findings. B‐type (BNP), N‐terminal pro‐B‐type (N‐BNP) and N‐terminal pro‐Atrial (N‐ANP) natriuretic peptides were assayed using in‐house immunoluminometric assays.

Results:

Of the considered clinical variables, only gender and heart rate (each P<0.005) were independently associated with levels of all three natriuretic peptides. Plasma levels of N‐ANP (15%), BNP (25%) and N‐BNP (75%) were higher in women compared to men. An increase in heart rate of 10 bpm corresponded to a reduction of 9% in N‐ANP or BNP and a 15% reduction in N‐BNP. Each 10 years of age was associated with 16% and 74% increase in ANP and N‐BNP levels, respectively, but no increase in plasma BNP. Left ventricular ejection fraction could be assessed in 582 (81%) subjects and correlated positively with N‐ANP (rs=6.48×10−3, P<0.001) and BNP (rs=2.4×10−2, P<0.001) but not N‐BNP (P=0.405). No parameter of diastolic function was associated with any peptide level.

Conclusions:

In this healthy population, plasma levels of N‐ANP, BNP and N‐BNP were variably influenced by clinical covariates. While all three peptides were higher in women, only N‐ANP and N‐BNP were influenced by age. Levels of all peptides were inversely correlated with heart rate. Using this immunoluminometric assay, plasma BNP is not influenced by age, in contrast to N‐ANP and N‐BNP. In constructing normal ranges for diagnostic use, covariates such as age and gender must be considered, in addition to the format of assay being used.
Adverse mortality effect of central sympathetic inhibition with sustained‐release moxonidine in patients with heart failure (MOXCON)
Authors: Cohn Jay N. , Pfeffer Marc A. , Rouleau Jean , Sharpe Norman , Swedberg Karl , Straub Matthias , Wiltse Curtis , Wright Theressa J. ,   for the MOXCON Investigators
Published: November 2003

Background:

The association between sympathetic activation and mortality in chronic heart failure and the favorable effect of beta blocking drugs has raised the possibility of therapeutic efficacy for central sympathetic inhibition with sustained‐release (SR) moxonidine, an imidazoline receptor agonist.

Methods:

A randomized double‐blind, placebo‐controlled trial was initiated in 425 centers in 17 countries with a plan to enter 4533 patients with New York Heart Association class II–IV heart failure and a reduced ejection fraction. Moxonidine SR or matching placebo was titrated to a target dose of 1.5 mg BID. The trial was powered to detect a 20% reduction in mortality, which required a total of 724 deaths.

Findings:

An early increase in death rate and adverse events in the moxonidine SR group led to premature termination of the trial because of safety concerns after 1934 patients were entered. Final analysis revealed 54 deaths (5.5%) in the moxonidine SR group and 32 deaths (3.4%) in the placebo group during the active treatment phase. Survival curves revealed a significantly (P=0.012) worse outcome in the moxonidine SR group. Hospitalization for heart failure, acute myocardial infarction and adverse events were also more frequent in the moxonidine SR group. Plasma norepinephrine was significantly decreased by moxonidine SR (−18.8% from baseline) vs. placebo (+6.9%).

Interpretation:

Early termination of the trial limited conclusions regarding the long‐term effects of central sympathetic inhibition. Nonetheless, the excess early mortality and morbidity suggest the likelihood of an adverse effect of moxonidine SR and raise concerns regarding the efficacy of generalized sympathetic inhibition in heart failure.
Josiane F. Hamers and Michel H.A. Blanc,
Bilinguality and bilingualism. 2nd ed. Cambridge:
Cambridge University Press, 2000. Pp. xiv + 468 pages. Hb $90.00,
pb $30.00.
Authors: Muysken, Pieter
Published: November 2003

This is the second edition of a very impressive
handbook that was published first in French in 1983, and
subsequently in English in 1989. This new edition was prepared
directly in English. Josiane Hamers is Professor of
Psycholinguistics and Bilingualism at the Université
de Laval, Québec, and Michel Blanc is Emeritus Reader
of Applied Linguistics and Bilingualism at Birkbeck College,
University of London.
John F. A. Sawyer and J. M.Y. Simpson (eds.),
Concise encyclopedia of language and religion. Amsterdam:
Elsevier, 2001. Pp. 612. Hb $194.50.
Authors: Tomlinson Matt
Published: November 2003

The Concise encyclopedia of language and
religion is distilled from the Encyclopedia of language
and linguistics, published in ten volumes in 1994. In their
preface, editors John F. A. Sawyer and J. M.Y. Simpson note
that more than 110 new articles have been written for this concise
edition, presumably to shift the focus from language alone to
the nexus of language and religion. Unfortunately, the book
reads like a philological encyclopedia that has seen a monk
scribbling in the margins, adding “religion” bits
copiously but not integrating them fully into the corpus on
language.
Barry Hallen, The Good, The Bad and The Beautiful.
Discourse about Values in Yoruba Culture. Bloomington:
Indiana University Press. 2001. Pp. 219. Hb $39.95.
Authors: Agyekum Kofi
Published: November 2003

This book combines culture, philosophy and
linguistics by examining everyday language. It concentrates
on the semantic interrelations between aspects of epistemic,
moral and aesthetic values of a person's life in Yoruba
society. The book contains six chapters and an appendix of
Yoruba-language quotations.
Zoltán Kövecses, Metaphor: A practical
introduction. New York: Oxford University Press, 2002.
Pp. xvi, 285. Pb. $19.95.
Authors: Lin Chienjer Charles
Published: November 2003

This is the first textbook on metaphor to
appear after the cognitive linguistic revolution of metaphorical
research launched two decades ago by Lakoff & Johnson with
their pioneering work, Metaphors we live by. Much
scholarship has since been devoted to this paradigm of research.
Twenty years have passed, and Kövecses takes this as a
good time to summarize the development of the field. Writing
a textbook on metaphor certainly reflects the maturation of
the study of metaphor within the cognitive linguistic tradition.
Targeted readers are undergraduate and graduate students with
interests in metaphor and cognitive linguistics. Experienced
researchers may also find this book helpful in motivating new
ideas.
Nikolay Vakhtin. Jazyki narodov severa v XX veke:
Ocherki jazykovogo sdviga [Languages of
the Peoples of North in the 20th century: Outline of the language
shift]. St. Petersburg: Dmitry Bulanin, 2001. Pp.
344. HB, n.p.
Authors: Perehvalskaya Elena
Published: November 2003

It would be unjust to say that languages of
ethnic minorities of Siberia and the Far East of Russia have
not received the attention of linguists and anthropologists,
yet until now there has been no book that has gathered, classified,
and compared data on the sociolinguistic situation of these
minorities over the whole Soviet period. This is the topic of
Vakhtin's new book. It deals almost exclusively with the
exterior aspect of the history of the languages; it does not
analyze structural changes in the languages themselves.
Joy Kreeft Peyton, Donald A. Ranard, & Scott
McGinnis (eds.), Heritage languages in America: Preserving
a national resource. Washington, DC: Center for Applied
Linguistics and Delta Systems, 2001. Pp. vi, 327. Pb $20.95.
Authors: Dutkova-Cope Lida
Published: November 2003

This volume, a product of the First National Conference on Heritage
Languages in America, held in Long Beach, California, in 1999, opens
with the editors' introduction, followed by fourteen chapters within
five thematic sections: “Defining the field,”
“Shaping the field,” “Educational issues,”
“Research and practice,” and “A call to
action.” Together, they make a compelling case for the
need to preserve and exploit heritage languages in the US as
a national resource. The book provides a comprehensive overview
of pressing issues and challenges within the growing field of
heritage language (henceforth HL) education, and it successfully
demonstrates “why those who are involved in the heritage
language movement believe that it is important for the United
States to preserve its non-English languages” (5). The
volume is intended primarily for “educators, community
leaders, researchers, grant makers and policymakers” (5),
though its clear, nontechnical language makes it accessible
to any reader interested in the subject. Its effective thematic
organization, likely to appeal to both novice and expert readers,
and its overall coherence, accentuated by ample cross-referencing,
testify to careful editorial preparation and suggest the desire
of all involved to speak with one voice as they build their
case and issue a call for action on behalf of heritage languages
in the US.
Kirk Hazen. Identity and ethnicity in the rural
South: A sociolinguistic view through past and present
Be. Durham, NC: Duke University Press for the American Dialect
Society, 2000. Pp. xii, 178. Pb $20.00.
Authors: José Brian
Published: November 2003

This book is the revised version of Hazen's 1997
Ph.D. dissertation at the University of North Carolina
(Chapel Hill). In it, Hazen investigates the linguistic behavior
of three ethnic groups in Warren County, North Carolina, both
individually and collectively, with respect to copula absence
and leveling of past be, with the aim of ascertaining
the linguistic boundaries that delineate the ethnic groups.
These ethnic groups are African Americans (comprising 57% of
the overall population in the 1990 Census), European Americans
(38%), and Native Americans (4%). In addition to ethnicity,
Hazen considers the influence of age, sex, and cultural identity.
He situates his data and findings in the broader sociolinguistic
context by discussing, for example, the contributions that they
make to the origins debate and the divergence/convergence
debate surrounding African American Vernacular English (AAVE).
Perhaps the two most significant contributions of the study,
however, are the discussion of wont as an innovative
variant descended from wasn't, a past-tense corollary
of present tense ain't (cf. Hazen 1998), and the
discussion of the influence of cultural identity on
sociolinguistic variation (cf. Hazen 2002).
Gender, publication and citation in sociolinguistics and
linguistic anthropology: The construction of a scholarly canon
Authors: McELHINNY BONNIE , HOLS MARIJKE , HOLTZKENER JEFF , UNGER, SUSANNE , HICKS CLAIRE
Published: November 2003

Feminist scholars have begun to ask how existing
conceptual schemes and organizational structures in academic
disciplines have excluded women and feminist ideas, and to provide
suggestions for transformation. One strand of this work has
been the exploration of how canons of thought are constructed
in such fields as economics, sociology, and sociocultural
anthropology. This article begins such an investigation for
sociolinguistics and linguistic anthropology by reviewing how
gender correlates with publication and citation over a 35-year
period (1965–2000) in five key journals, and in 16 textbooks
published in the 1990s. It describes some marked differences
in the publication of works by women and on gender in the five
journals, as well as some significant differences in the degree
to which men and women cite the work of women. It also considers
how the rate of publication of articles on sex, gender, and
women is correlated with publication of female authors. It
concludes with a discussion of the implications of this study
for changing institutional practices in our field.
HEALTH CARE RESOURCE USE AND STROKE OUTCOME
Authors: Asplund Kjell , Ashburner Sharron , Cargill Kathy , Hux Margaret , Lees Ken , Drummond for the GAIN International Investigators Michael
Published: November 2003

Background and Purpose: Outcome in patients hospitalized for acute stroke varies considerably between populations. Within the framework of the GAIN International trial, a large multicenter trial of a neuroprotective agent (gavestinel, glycine antagonist), stroke outcome in relation to health care resource use has been compared in a large number of countries, allowing for differences in case mix.

Methods: This substudy includes 1,422 patients in 19 countries grouped into 10 regions. Data on prognostic variables on admission to hospital, resource use, and outcome were analyzed by regression models.

Results: All results were adjusted for differences in prognostic factors on admission (NIH Stroke Scale, age, comorbidity). There were threefold variations in the average number of days in hospital/institutional care (from 20 to 60 days). The proportion of patients who met with professional rehabilitation staff also varied greatly. Three-month case fatality ranged from 11% to 28%, and mean Barthel ADL score at three months varied between 64 and 73. There was no relationship between health care resource use and outcome in terms of survival and ADL function at three months. The proportion of patients living at home at three months did not show any relationship to ADL function across countries.

Conclusions: There are wide variations in health care resource use between countries, unexplained by differences in case mix. Across countries, there is no obvious relationship between resource use and clinical outcome after stroke. Differences in health care traditions (treatment pathways) and social context seem to be major determinants of resource use. In making comparisons between countries, great care should be exercised in using outcome variables as indicators of quality of stroke care.
IMPACT OF GENE PATENTS ON THE COST-EFFECTIVE DELIVERY OF CARE: THE CASE OF BRCA1 GENETIC TESTING
Authors: Sevilla Christine , Julian-Reynier Claire , Eisinger François , Stoppa-Lyonnet Dominique , Bressac-de Paillerets Brigitte , Sobol Hagay , Moatti Jean-Paul
Published: November 2003

Background: In 1994/95, two genes, BRCA1/2, associated with a predisposition to breast or ovarian cancer were identified. Genetic testing of deleterious BRCA1/2 mutations consequently can be proposed to individuals with a family history of breast or ovarian cancer to identify who is at risk. The granting of U.S. patents on BRCA1/2 to a privately owned company has led to the monopoly use of a unique technique (Direct Sequencing of the gene, DS) for BRCA1/2 testing in this country. Alternative strategies using prescreening techniques, however, have been experienced worldwide.

Methods: On the basis of data collected at three laboratories of French public hospitals, we carried out a cost-effectiveness study comparing DS to 19 alternative strategies with the number of deleterious BRCA1 mutations detected as the outcome.

Results: Results show that the DS strategy presents the highest average cost per mutation detected (9,882.5 °) and that there exist strategies using prescreening techniques that can reach similar effectiveness while reducing total costs. Moreover, other strategies can obtain a four- to sevenfold reduction in the average cost per mutation detected as soon as some rates of false negatives (2% to 13%) are deemed to be acceptable.

Conclusions: Results suggest that gene patents with a very broad scope, covering all potential medical applications, may prevent health care systems from identifying and adopting the most efficient genetic testing strategies due to the monopoly granted for the exploitation of the gene. Policy implications for regulatory authorities, in the current context of the extension of BRCA1/2 patents in other countries, are discussed.
COMPARING COMMUNITY-PREFERENCE–BASED AND DIRECT STANDARD GAMBLE UTILITY SCORES: EVIDENCE FROM ELECTIVE TOTAL HIP ARTHROPLASTY
Authors: Feeny David , Blanchard Christopher , Mahon Jeffrey L. , Bourne Robert , Rorabeck Cecil , Stitt Larry , Webster-Bogaert Susan
Published: November 2003

Objectives: Do utility scores based on patient preferences and scores based on community preferences agree? The purpose is to assess agreement between directly measured standard gamble (SG) utility scores and utility scores from the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) systems.

Methods: Patients were assessed repeatedly throughout the process of waiting to see a surgeon, waiting for surgery, and recovery after total hip arthroplasty (THA). Group mean scores are compared using paired t-tests. Agreement is assessed using the intraclass correlation coefficient (ICC).

Results: The mean SG, HUI2, and HUI3 (SD) scores at assessment 1 are 0.62 (0.31), 0.62 (0.19), and 0.52 (0.21); n=103. At assessment 2, the means are 0.67 (0.30), 0.68 (0.30), and 0.58 (0.22); n=84. There are no statistically significant differences between group mean SG and HUI2 scores. Mean SG and HUI3 scores are significantly different. ICCs are low.

Conclusions: At the mean level for the group, SG and HUI2 scores match closely. At the individual level, agreement is poor. HUI2 scores were greater than HUI3 scores. HUI2 and HUI3 are appropriate for group level analyses relying on community preferences but are not a good substitute for directly measured utility scores at the individual leve.
ASSESSMENT OF DIAGNOSTIC TESTS TO INFORM POLICY DECISIONS-VISUAL ELECTRODIAGNOSIS
Authors: Johnston Renea V. , Burrows Elizabeth , Raulli Alexandra
Published: November 2003

Objectives: To conduct a systematic review of the evidence for the effectiveness of five visual electrodiagnostic tests to inform the Medical Services Advisory Committee (MSAC) of the Department of Health and Ageing (Australia) in its decision in allocating public funding for new technologies.

Methods: We searched the biomedical literature to identify English-language articles published from 1966 to September 2000. We assessed validity of methodology of included studies against the following criteria: investigators (i) compared test with an appropriate reference test; (ii) tested an appropriate spectrum of patients; (iii) masked assessment of study and reference tests; (iv) measured the study test independently of clinical information; and (v) measured the reference test before any interventions.

Results: Sixty-one articles met inclusion criteria for critical appraisal: nineteen were cross-sectional studies that compared a study test with another test, thirty-four were case-control studies that compared a test in a group of patients with an eye disease to a group of subjects without eye disease, and eight studies were case series. None of the included studies met all of the validity criteria. Only four studies provided enough information to calculate diagnostic characteristics but were flawed due to inclusion of patients already diagnosed with disease or lack of an appropriate reference test and, thus, overestimated test accuracy.

Conclusions: Identified studies did not provide sufficient valid evidence of the clinical value of the five visual tests in diagnosing diseases of the retina or optic nerve. Thus, MSAC recommended that the tests not be supported by public funding.
Formal methods for the validation of automotive product configuration data
Authors: SINZ CARSTEN , KAISER ANDREAS , KÜCHLIN WOLFGANG
Published: November 2003

In the automotive industry, the compilation and maintenance of correct product configuration data is a complex task. Our work shows how formal methods can be applied to the validation of such business critical data. Our consistency support tool BIS works on an existing database of Boolean constraints expressing valid configurations and their transformation into manufacturable products. Using a specially modified satisfiability checker with an explanation component, BIS can detect inconsistencies in the constraints set and thus help increase the quality of the product data. BIS also supports manufacturing decisions by calculating the implications of product or production environment changes on the set of required parts. In this paper, we give a comprehensive account of BIS: the formalization of the business processes underlying its construction, the modifications of satisfiability-checking technology we found necessary in this context, and the software technology used to package the product as a client–server information system.
Involvement of glutamate in ischemic neurodegeneration in isolated
retina
Authors: IZUMI YUKITOSHI , HAMMERMAN SETH B. , KIRBY CHARITY O. , BENZ ANN M. , OLNEY JOHN W. , ZORUMSKI CHARLES F.
Published: November 2003

Retinal ischemia, a major cause of visual loss, is believed to result
from overexcitation of glutamate receptors. However, under euglycemic
and normoxic conditions, exogenously applied glutamate is not
neurotoxic in the retina. Under such conditions, exogenous glutamate
typically causes glia swelling and requires very high concentrations to
produce neurotoxicity. To determine whether ischemic conditions enhance
the neurotoxicity of endogenous and exogenous glutamate, we examined
the effects of simulated ischemia (deprivation of both glucose and
oxygen) on retinal morphology and lactate dehydrogenase (LDH) release.
In an ex vivo rat retinal preparation, glutamate was
administered during simulated ischemia in the presence of riluzole, an
inhibitor of glutamate release. Deprivation of both glucose and oxygen
for 60 min at 30°C produced severe acute neurodegeneration. This
neurodegeneration, characterized by bull's eye formation in the
inner nuclear layer and spongy appearance in the inner plexiform layer,
was prevented by the combination of MK-801 and DNQX, antagonists of
N-methyl-D-aspartate (NMDA) and non-NMDA receptors, indicating that the
damage results from activation of both glutamate receptors. We also
found that administration of glutamate pyruvate transaminase (alanine
aminotransaminase) with pyruvate diminished the neurodegeneration
during simulated ischemia. Furthermore, riluzole, an inhibitor of
glutamate release, attenuated the neurodegeneration, suggesting the
importance of endogenous glutamate in ischemic damage. In the presence
of riluzole and simulated ischemia, exogenously applied glutamate
failed to cause Müller cell swelling but was extremely neurotoxic.
These results suggest that simulated ischemia enhances
glutamate-mediated neurotoxicity in part by depressing glutamate
uptake. When glutamate transport is impaired, sub-millimolar glutamate
concentrations become profoundly neurotoxic.
Spontaneous regenerative activity in mammalian retinal bipolar
cells: Roles of multiple subtypes of voltage-dependent Ca2+
channels
Authors: MA YU-PING , PAN ZHUO-HUA
Published: November 2003

Patch-clamp recordings were used to investigate the properties of the
regenerative activity in acutely isolated bipolar cells from the rat
retina. Spontaneous, pacemaker-like membrane potential oscillations
were observed in all rod bipolar cells and the majority of cone bipolar
cells. The waveform of the regenerative potential was stereotypical but
distinct among different bipolar cell groups, especially between rod
and cone bipolar cells. The spontaneous activity was completely blocked
by Co2+, suggesting that Ca2+ influx through
voltage-dependent Ca2+ channels was required for initiating
such activity. Ca2+-induced Ca2+ release, however,
was not found to be involved. The spontaneous activity was also blocked
by mibefradil, a T-type Ca2+ channel antagonist. In contrast,
application of nimodipine, an L-type Ca2+ current antagonist,
affected mainly the waveform of the regenerative potential. This study
shows that mammalian retinal bipolar cells in isolation are also capable
of generating Ca2+-dependent spontaneous regenerative potential.
However, T-type Ca2+ channels appear to be essential for the
initiation of the spontaneous activity in mammalian bipolar cells.
Evidence for low-voltage-activated (LVA) calcium currents in the
dendrites of tiger salamander retinal ganglion cells
Authors: HENDERSON DORI , MILLER ROBERT F.
Published: November 2003

We have evaluated the spatial distribution of low-voltage-activated
calcium currents in ganglion cells of the tiger salamander retina.
Whole-cell recordings were obtained from ganglion cells in a retinal
slice preparation and from acutely dissociated ganglion cells that were
identified through retrograde dye injection. In single dissociated
cells, we estimated the magnitude (pA) and current density (pA/pF)
of LVA currents in ganglion cells, both with and without dendritic
processes. Ganglion cells that retained a portion of their dendritic
arbor had larger LVA calcium currents and higher LVA current densities
than those which lacked processes. When cell capacitance measurements
were used to derive the surface area of the soma and dendritic
processes, we concluded that a higher LVA current density was present
in the dendrites; we estimate that, on average, the current density in
the dendrites is approximately five times that of the soma. The
presence of a significant density of LVA calcium channels in the
dendrites of ganglion cells suggests that they could be involved in a
number of cellular functions, including dendritic integration of
synaptic currents, impulse generation, and homeostatic functions
related to changes in the intradendritic calcium concentration.
Cell density ratios in a foveal patch in macaque retina
Authors: AHMAD KAREEM M. , KLUG KARL , HERR STEVE , STERLING PETER , SCHEIN STAN
Published: November 2003

We examine the assumptions that the fovea contains equal numbers of
inner (invaginating or ON) and outer (flat or OFF) midget bipolar cells
and equal numbers of inner and outer diffuse bipolar cells. Based on
reconstruction from electron photomicrographs of serial thin sections
through the fovea of a macaque monkey, we reject both assumptions.
First, every foveal L and M cone is presynaptic to one inner and one
outer midget bipolar cell; however, S cones are presynaptic to one
outer but no inner midget bipolar cell. Second, we measure the density
of all foveal cells in the same patch of fovea, affording accurate cell
density ratios. For each foveal cone pedicle, at a density of 26,500
mm−2, there is close to one (0.88) outer diffuse
bipolar cell but only 0.40 inner diffuse bipolar cells. This
asymmetry may be related to differences in resolution and
sensitivity for light increments and decrements. We also
find one (1.01) Müller cell, one (1.01) amacrine cell in the inner
nuclear layer, and close to one (0.83) horizontal cell for each cone
pedicle. In addition, for each S cone, there are two inner S-cone
bipolar cells and two small bistratified ganglion cells. In total,
there are 3.4 cone bipolar cells per cone but only 2.6 ganglion cells
per cone. The latter ratio is enough to accommodate one midget ganglion
cell for each midget bipolar cell.
Response to “Reading Futility: Reflections on a Bioethical
Concept” by Donald Joralemon (CQ Vol 11, No 2), The Rise and Fall
of Death: The Plateau of Futility
Authors: Schneiderman Lawrence J. , Teetzel Holly , Gilmer Todd
Published: November 2003

Researchers tracking social trends have discovered a remarkable
labor-saving device called the computer. They sit down before the instrument,
call up a search engine, enter a key word that they believe represents the
trend, and count the number of articles aroused by that key word. They track
these numbers over a period of time and even graph them. Those who dislike a
certain concept are happy to report the concept's rise and fall. Such has
occurred with two articles, one of which appeared in CQ, reporting
the rise and fall of medical futility. We are impressed with the power of this
research methodology, which seems capable of eliminating concepts, even when
our own more labor-intensive yet apparently less perceptive daily experience
finds evidence of their existence all around us.
Abstracts of Note: The Bioethics Literature
Authors: Iserson Kenneth V.
Published: November 2003

This section is meant to be a mutual effort. If you find an article you
think should be abstracted in this section, do not be bashful—submit
it for consideration to feature editor Kenneth V. Iserson care of CQ. If you
do not like the editorial comments, this will give you an opportunity to
respond in the letters section. Your input is desired and anticipated.
A View of Bioethics from Down Under
Authors: ANKENY RACHEL A.
Published: November 2003

When I immigrated to Australia from the United States a few years
ago, at first I found many similarities between the countries. But
underneath the apparent similarities, notably a shared language, lay
much deeper differences in history, politics, and culture that have
considerable impacts on attitudes and approaches to issues in bioethics
and medicine. For instance, debates continue regarding cloning and
embryonic stem cell research, particularly given the long history of
research in reproductive medicine and reproductive technologies in
Australia. Although there are individuals and groups opposed to such
research on grounds associated with pro-life or anti-abortion stances,
the discussions more often hinge on what should be funded by the
government and eventually what should be provided to all within the
public system of healthcare. This theme is one common thread that
unites many current controversies in bioethics, but perhaps not for the
reasons that an outsider might at first expect. Indeed, allocation of
limited resources is part of what is considered relevant, but money is
rarely presented as the decisive issue in these debates.
Instead, considerations such as what is medically necessary (based on a
broad definition of what is medical), what contributes to a “good
life” (as defined by what are increasingly heterogeneous
community standards), and how to respect and enable fulfillment of
autonomous decisions by individuals and families in this rapidly
changing context are key to many of the disputes. This brief report is
necessarily selective, but it is designed to give a flavor of the terms
of the debates as they are currently developing.
Israel: Bioethics in a Jewish-Democratic State
Authors: GROSS MICHAEL L. , RAVITSKY VARDIT
Published: November 2003

Unlike most Western nations, Israel does not recognize full
separation of church and state but seeks instead a gentle fusion of
Jewish and democratic values. Inasmuch as important religious norms
such as sanctity of life may clash with dignity, privacy, and
self-determination, conflicts frequently arise as Israeli lawmakers,
ethicists, and healthcare professionals attempt to give substance to
the idea of a Jewish-democratic state. Emerging issues in Israeli
bioethics—end-of-life treatment, fertility, genetic research, and
medical ethics during armed conflict—highlight this conflict
vividly.
Cognitive functioning and psychiatric symptomatology in patients with chronic hepatitis C
Authors: Hilsabeck Robin C. , Hassanein Tarek I. , Carlson Meghan D. , Ziegler Elizabeth A. , Perry William
Published: November 2003

Hepatitis C virus (HCV) infection is a major public-health-care problem, with over 170 million infected worldwide. Patients with chronic HCV infection often complain of various cognitive problems as well as symptoms of depression, anxiety, and fatigue. Relatively little is known, however, about the specific cognitive deficits that are common among HCV patients, and the influence of psychiatric symptomatology on cognitive functioning. In the current study of 21 chronically infected HCV patients, we assessed subjective cognitive dysfunction, depression, anxiety, and fatigue and compared these symptom areas to cognitive tests assessing visuoconstruction, learning, memory, visual attention, psychomotor speed, and mental flexibility. Results revealed that cognitive impairment ranged from 9% of patients on a visuoconstruction task to 38% of patients on a measure of complex attention, visual scanning and tracking, and psychomotor speed, and greater HCV disease severity as indicated by liver fibrosis was associated with greater cognitive dysfunction. Objective cognitive impairment was not related to subjective cognitive complaints or psychiatric symptomatology. These findings suggest that a significant portion of patients with chronic HCV experience cognitive difficulties that may interfere with activities of daily living and quality of life. Future research using cognitive measures with HCV-infected patients may assist researchers in identifying if there is a direct effect of HCV infection on the brain and which patients may be more likely to progress to cirrhosis and hepatic encephalopathy. (JINS, 2003, 9, 847–854.)