bluuebunny/crossref_metadata_2025 huggingface dataset:
Persuasive constraint and expert versus non‐expert influence in intention to quit smoking
Authors: Falomir‐Pichastor Juan Manuel , Butera Fabrizio , Mugny Gabriel
Published: October 2002

In a 2 × 2 design, after listing important personal reasons for smoking, 70 smokers were randomly told either that they had sufficient reasons for smoking (low internal constraint to change) or that they did not have sufficient reasons (high internal constraint to change) and were exposed to an anti‐smoking message from a source with either expert (high external constraint to change) or non‐expert (low external constraint to change) status. The main dependent variable was change in intention to give up smoking. The analyses revealed the predicted interaction between external and internal constraint: High internal constraint increased non‐expert influence but not expert influence. Supplementary analysis showed that, when internal constraint was high, non‐expert influence was related to the perceived quality of the message whereas when internal constraint was low, expert influence was related to the source's perceived motivation to inform, i.e. rather than to convince. These results were predicted on the basis of the link that targets establish in social influence settings between constraints to change that are internal (i.e. related to their personal beliefs, feelings or attitudes) and those that are external (i.e. related to the characteristics of the persuasive communication such as the status of the source). Copyright © 2002 John Wiley & Sons, Ltd.
The relationship between acculturation strategies, relative fit and intergroup relations: immigrant‐majority relations in Germany
Authors: Zagefka Hanna , Brown Rupert
Published: October 2002

This study examined the impact of the acculturation strategy preferences of both immigrants and host society on intergroup relations. It was expected that integration would lead to the best outcome for both groups. Moreover, it was tested whether the relative ‘fit’ between host society and immigrant strategy preference would predict intergroup relations. The predictive power of two different operationalisations of fit was compared. School students (193 German host society members and 128 immigrants to Germany) participated in a questionnaire study. Findings revealed that both acculturation strategies of one group and relative ‘fit’ between immigrant and host society strategy preference were predictive of intergroup relations. In general, a strategy of integration was associated with more favourable intergroup relations in both groups, and a mismatch between host and immigrant preferred strategies yielded the most negative outcomes. Copyright © 2002 John Wiley & Sons, Ltd.
Asymmetrical impact: vigilance for differences and self‐relevant stimuli
Authors: Olson James M. , Janes Leslie M.
Published: October 2002

We hypothesized that people are ‘vigilant’ for differences between stimuli. In particular, we compared the reactions elicited by unexpected differences versus unexpected similarities. Participants imagined themselves in several situations where they learned something unexpected. This unexpected information showed either that two things previously thought to be similar were actually different or that two things previously thought to be different were actually similar. Also, the new information was either beneficial, neutral, or detrimental to the perceiver. Participants indicated for each situation how surprised they would be and how they would feel. Unexpected differences were rated as more surprising than unexpected similarities for positive and negative events, though not for neutral events. Participants also reported that beneficial differences would produce more positive affect than beneficial similarities, whereas detrimental differences would produce more negative affect than detrimental similarities. These findings support the asymmetrical impact hypothesis that differences have more psychological impact than similarities. Copyright © 2002 John Wiley & Sons, Ltd.
Smiling and self‐presentation of men and women for job photographs
Authors: Vrugt Anneke , Van Eechoud Marieke
Published: October 2002

The present research studied the factors that influence the smiling behaviour of men and women. We assumed that men and women who actively engage in self‐presentation use smiling as a strategy to take advantage of the expectations of others in order to realize their own goals. In the research situation, the participants imagined that they wanted to obtain a certain part‐time job. We expected that gender‐role expectations, the gender‐typing and status of the job in question, and the importance of social contacts for carrying out the job would influence the extent to which men and women would smile for a photo to be sent with a job application. The results partly support this expectation: men and women smiled more in response to a low‐status job than to a high‐status job; women smiled more in response to a job in which social contacts are important than to a job in which social contacts are unimportant; and women smiled more than men in response to a feminine low‐status job in which social contacts are important. Copyright © 2002 John Wiley & Sons, Ltd.
Photoclastogenicity—an improved protocol, its validation, and investigation of the photogenotoxicity of DMBA
Authors: Murli H. , Aardema M. , Lawlor T. , Spicer C.
Published: October 2002

An improved protocol was developed to detect light‐induced clastogenic photoproducts in Chinese hamster ovary (CHO) cells. Dishes (60 mm) containing cells and the test material or vehicle control in 3 mL of phosphate‐buffered saline were exposed to light using a SUNTEST CPS solar simulation unit. Importantly, cells were exposed at about 25 cm from the light source, thereby allowing a short exposure time of 2 min. With this exposure the assay was conducted with lids removed during the UV exposure with minimal risk of contamination. After preliminary experiments an exposure of 165.6 mJ/cm2 UVA: 17.0 mJ/cm2 UVB was selected for treatments with the different phototoxins. Under these exposure conditions about 10–15% aberrant cells were induced in vehicle control cultures with no or minimal cytotoxicity. The well‐known photoclastogens 8‐methoxypsoralen (8‐MOP) and chlorpromazine (CLZ) were tested. In agreement with published data, 8‐MOP and CLZ were clastogenic (lowest observed effect level, LOEL, was 0.0159 μg/mL and 1.03 μg/mL, respectively). In the absence of UV, 8‐MOP was clastogenic at a much higher concentration (LOEL 251 μg/mL without UV vs. 0.0159 μg/mL with UV) while CLZ was negative up to a toxic concentration of 35 μg/mL. 7,12‐Dimethylbenz[a]anthracene (DMBA), which is photomutagenic in bacteria, was clastogenic at ≥0.005 μg/mL with UV light (without S9) and at ≥2.53 μg/mL with S9 (without UV light). These results demonstrate the utility of the protocol for the detection of photoclastogenicity and expand the characterization of DMBA's photogenotoxic activity. Environ. Mol. Mutagen. 40:41–49, 2002. © 2002 Wiley‐Liss, Inc.
Development and application of a fatty acid based microbial community structure similarity index
Authors: Werker Alan , Hall Eric
Published: October 2002

This article presents an index of similarity that has application in monitoring relative changes of complex microbial communities for the purpose of understanding the impact of community instability in biological wastewater treatment systems. Gas chromatographic data quantifying microbial fatty acid esters extracted from biosolids samples can be used to infer the occurrence of changes in mixed culture community structure. One approach to rapidly assess the relative dissimilarity between samples is to calculate a similarity index scaled between 0 and 1. The many arbitrary scales that are associated with the available calculation methods for similarity indices limits the extent of application. Therefore, a specialized index of similarity was derived from consideration of the measurement errors associated with the chromatographic data. The resultant calculation method provides a clear mechanism for calibrating the sensitivity of the similarity index, such that inherent measurement variability is accommodated and standardization of scaling is achieved. The similarity index sensitivity was calibrated with respect to an effective gas chromatographic peak coefficient of variation, and this calibration was particularly important for facilitating comparisons made between different systems or experiments. The proposed index of similarity was tested with data acquired from a recently completed study of contaminant removal from pulp mill wastewater. The results suggest that this index can be used as a screening tool to rapidly process microbial fatty acid (MFA) compositional data, with the objective of making preliminary identification of underlying trends in (MFA) community structure, over time or between experimental conditions. Copyright © 2002 John Wiley & Sons, Ltd.
Active viscous damping system with amplifying braces for control of MDOF structures
Authors: Gluck J. , Ribakov Y.
Published: October 2002

The development and the applications of an active controlled viscous damping device with amplifying braces are described. The system of the dampers, defined as active viscous damping system (AVDS), connected to an amplifying brace (AB) is presented herein. Instantaneous control theory with velocity and acceleration feedback is used to obtain the control forces at each time step during an excitation. Control of the damping forces is possible due to the mechanical structure of the proposed AVDS, and the connection to the AB. The proposed system can be efficiently used to enhance the damping of a structure without modifying its stiffness. The added damping forces can be adjusted in a wide range. The efficiency of the presented system is demonstrated by a numerical simulation of a seven‐storey building subjected to earthquakes. The simulation shows a considerable reduction of control forces required for control to the AVDS with AB, compared to the same system without AB. Copyright © 2002 John Wiley & Sons, Ltd.
A rare landform: Yerköprü travertine bridges in the Taurids Karst Range, Turkey
Authors: Bayari C. Serdar
Published: October 2002

Two examples of travertine bridges are observed at 8 to 15 m above stream level in the Lower Zamanti Basin, Eastern Taurids, Turkey. Yerköprü‐1 and Yerköprü‐2 bridges are currently being deposited from cool karstic groundwaters with log PCO2 > 10−2 atm. The surface area and the total volume of travertine in Yerköprü‐1 bridge are 4350 m2 and 40 000 m3, whereas the values for Yerköprü‐2 are 2250 m2 and 20 000 m3, respectively. The interplay of hydrogeological structure, local topography, calcite‐saturated hanging springs, algal activity and rapid downcutting in the streambed appear to have led to the formation of travertine bridges. Aeration through cascades and algal uptake causes efficient carbon dioxide evasion that enhances travertine formation. Algal curtains aid lateral development of travertine rims across the stream. Model calculations based on a hypothetical deposit in the form of a half‐pyramid implied that lateral development should have occurred from both banks of the stream in the Yerköprü‐1 bridge, whereas one‐sided growth has been sufficient for Yerköprü‐2. The height difference between travertine springs and the main stream appears to be a result of Pleistocene glaciation during which karstic base‐level lowering was either stopped or slowed down while downcutting in the main stream continued. Copyright © 2002 John Wiley & Sons, Ltd.
Calculating basal temperatures in ice sheets: an Excel spreadsheet method
Authors: Glasser Neil F. , Siegert Martin J.
Published: October 2002

The flow of ice sheets and their geomorphological impact is greatly influenced by their basal thermal regime. Calculations of basal temperatures in ice sheets are therefore fundamental in evaluating glacier dynamics and in determining the spatial distribution of zones of erosion and deposition beneath ice masses. Calculations of basal temperatures are not frequently attempted, however, primarily because of the techniques required to solve the heat conduction equation between the ice surface and the base. This paper describes a new Excel spreadsheet method of solving this equation that can readily be applied to both former and contemporary ice sheets. The application of the spreadsheet is illustrated with two examples. The first provides a calculation of basal thermal regime beneath the north eastern part of the Scottish ice sheet during the last glacial maximum; the second shows how basal ice temperatures can be calculated beneath the modern Antarctic ice sheet. Copyright © 2002 John Wiley & Sons, Ltd.
Missing links: Eugène Dubois and the origins of paleoanthropology
Authors: Shipman Pat , Storm Paul
Published: October 2002

Examining the origins of various scientific fields may help to identify particular individuals whose thought, work, and discoveries have had a disproportionately large influence. Such individuals seem to serve as catalysts for a wider set of intellectual reactions, which then give rise to an entire field of study. In this paper, we propose explicit criteria for recognizing the founders of new fields. We contend that Eugène Dubois, best known as the man who found the “missing link” between apes and humans, should be recognized as one of the founding fathers of paleoanthropology.
Is the medium the message? Biological traits and their regulation
Authors: Weiss Kenneth
Published: October 2002

Much about the nature of biological processes is logically necessary but functionally arbitrary. What does this mean about biology?
Wastewater Treatment during Contingency Operations: The Balkans Challenge
Authors: Zettersten Garry C. , Best Raymond K. , Dale Debra A.
Published: October 2002

This article focuses on wastewater treatment during contingency operations at Eagle Base in Bosnia and Camp

Monteith and Camp Bondsteel in Kosovo. Operating in areas with limited regulation, U.S. forces in Europe have again

shown “the ability to demonstrate and incorporate environmental stewardship in all aspects of the

mission.” Over the past four years, environmental protection efforts associated with Balkan contingency

operations have evolved from an “extra duty” to a mission enabler and force protection issue. In the

process, U.S. Army Europe (USAREUR) has established and operates under the following principles:

(1) protect the force; (2) limit U.S. liability against claims; (3) spend

U.S. dollars wisely; and (4) demonstrate and incorporate environmental stewardship in all aspects of

the mission. © 2002 Wiley Periodicals, Inc.*
Hybrid Bioreactors for Decontamination of Water and Air
Authors: Boles Jeffrey L. , Gamble Johnny R.
Published: October 2002

The Tennessee Valley Authority (TVA) has developed and patented innovative Hybrid Bioreactors that

destroy water and air contaminants, with dramatic savings over existing technologies. Hybrid Bioreactors

accomplish single‐step destruction of contaminants without generating contaminated off‐gases or

other secondary waste streams. Contaminants destroyed include a wide variety of volatile organic compounds,

chlorinated solvents, and other compounds. The bioreactors can be used in a variety of applications ranging

from site restoration to industrial compliance. Treatment costs using Hybrid Bioreactors are generally less

than one‐tenth of costs reported at Superfund sites. A gas stream application of the new technology was

field‐demonstrated at Anniston Army Depot in a project funded by the U.S. Army Environmental Center. A

300‐cubic‐foot Hybrid Bioreactor is being demonstrated this year at TVA's Wetlands Complex

in Muscle Shoals, Alabama. Additional information is available at

http://www.tva.gov/environment/envservices/alw_biofilter.htm. © 2002 Wiley

Periodicals, Inc.*
A differential equation for approximate wall distance
Authors: Fares E. , Schröder W.
Published: October 2002

A partial differential equation to compute the distance from a surface is derived and solved numerically. The benefit of such a formulation especially in combination with turbulence models is shown. The details of the formulation as well as several examples demonstrating the influence of its parameters are presented. The proposed formulation has computational advantages and can be favourably incorporated into one‐ and two‐equation turbulence models like e.g. the Spalart–Allmaras, the Secundov or Menter's SST model. Copyright © 2002 John Wiley & Sons, Ltd.
Futures price limit moves as options
Authors: Holder Mark E. , Ma Christopher K. , Mallett James E.
Published: October 2002

This note demonstrates that an asset's price in an environment with price limit rules can be replicated by

the price of a portfolio consisting of a riskless asset and two synthetic options. A procedure is developed to

unbundle the unobservable option values imbedded in the actual futures price and impute a theoretical true futures

price. Using this framework, evidence from the Treasury Bond futures market suggests that theoretical true futures

prices diverge from actual futures prices, on average, 3 h prior to the activation of price limit rules,

indicating that price limit moves might be predictable. The reversal of both the actual futures prices and the

theoretical futures prices back within the limit range after a limit move provides support for the possibility

that traders tend to overreact when market prices are near price limits. © 2002 Wiley Periodicals, Inc. Jrl

Fut Mark 22:901–913, 2002
Preferential expression of a mutant allele of the amplified MDR1 (ABCB1) gene in drug‐resistant variants of a human sarcoma
Authors: Chen Kevin G. , Lacayo Norman J. , Durán George E. , Wang Yan , Bangs C. Dana , Rea Susan , Kovacs Mary , Cherry Athena M. , Brown J. Martin , Sikic Branimir I.
Published: October 2002

Activation of the MDR1 (ABCB1) gene is a common event conferring multidrug resistance (MDR) in human cancers. We investigated MDR1 activation in MDR variants of a human sarcoma line, some of which express a mutant MDR1, which facilitated the study of allelic gene expression. Structural alterations of MDR1, gene copy numbers, and allelic expression were analyzed by cytogenetic karyotyping, oligonucleotide hybridization, Southern blotting, polymerase chain reaction, and DNA heteroduplex assays. Both chromosome 7 alterations and several cytogenetic changes involving the 7q21 locus are associated with the development of MDR in these sarcoma cells. Multistep‐selected cells and their revertants contain three‐ to six‐fold MDR1 gene amplification compared with that of the drug‐sensitive parental cell line MES‐SA and single‐step doxorubicin‐selected mutants. MDR1 gene amplification precedes the emergence of a mutant allele in cells that were coselected with doxorubicin and a cyclosporin inhibitor of P‐glycoprotein (P‐gp). Allele‐specific oligonucleotide hybridization showed that the endogenous mutant allele was present as a single copy, with multiple copies of the normal allele. Reselection of revertant cells with doxorubicin in either the presence or the absence of the P‐gp inhibitor resulted in exclusive reexpression of the mutant MDR1 allele, regardless of the presence of multiple wild‐type MDR1 alleles. These data provide new insights into how multiple alleles are regulated in the amplicon of drug‐resistant cancer cells and indicate that increased expression of an amplified gene can result from selective transcription of a single mutant allele of the gene. © Wiley‐Liss, Inc.
No evidence for hypermethylation of the hSNF5/INI1 promoter in pediatric rhabdoid tumors
Authors: Zhang Fan , Tan Lu , Wainwright Luanne M. , Bartolomei Marisa S. , Biegel Jaclyn A.
Published: October 2002

The hSNF5/INI1 gene on chromosome 22 has been implicated as a tumor suppressor gene in pediatric rhabdoid tumor, an aggressive malignancy that generally occurs in the first two years of life. The most common sites for tumor development are the brain and kidney. We and other investigators have identified deletions and mutations of the INI1 gene in the majority of rhabdoid tumors of the central nervous system, kidney, and extrarenal tissues. At least 20% of cases do not have genomic alterations of INI1, although expression at the RNA or protein level may be decreased. The aim of this study was to determine whether hypermethylation or mutation of the 5′ promoter region of INI1, or hypermethylation of CpG dinucleotides in a GC‐rich repeat region within the first intron, could account for the decreased expression of INI1 observed in these tumors. We employed bisulfite modification, polymerase chain reaction, and sequence analysis to determine the methylation status of the cytosine nucleotides in the predicted promoter region of the INI1 gene, and two GC repeat regions in intron 1. DNA from 24 tumors with or without coding‐sequence mutations was analyzed. None of the tumors demonstrated methylation of the promoter or intron 1 regions. This mechanism is unlikely to account for the inactivation of INI1 in rhabdoid tumors without coding‐sequence mutations. One tumor demonstrated a potential mutation in the promoter region, but further studies are required for determining its functional significance. © 2002 Wiley‐Liss, Inc.
Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components
Authors: Actor Bertrand , Cobbers J.M.J. Ludwig , Büschges Rainer , Wolter Marietta , Knobbe Christiane B. , Reifenberger Guido , Weber Ruthild G.
Published: October 2002

Gliosarcoma is a variant of glioblastoma multiforme characterized by two components displaying gliomatous or sarcomatous differentiation. We investigated 38 gliosarcomas for aberrations of tumor‐suppressor genes and proto‐oncogenes that are commonly altered in glioblastomas. Amplification of CDK4, MDM2, EGFR, and PDGFRA were found in 11% (4/35), 8% (3/38), 8% (3/38), and 3% (1/35) of the tumors, respectively. Nine of 38 gliosarcomas (24%) carried TP53 mutations. PTEN mutations were identified in 45% (9/20) of the investigated tumors. Twenty gliosarcomas were analyzed by comparative genomic hybridization (CGH). Chromosomal imbalances commonly detected were gains on chromosomes 7 (15/20; 75%), X (4/20; 20%), 9q, and 20q (3/20, 15% each); and losses on chromosomes 10 and 9p (7/20, 35% each), and 13q (3/20, 15%). Five different high‐level amplifications were mapped to 4q12–q21 (1 case), 6p21 (1 case), 7p12 (2 cases), proximal 12q (4 cases), and 14q32 (1 case) by CGH. Southern blot and/or differential PCR analyses identified amplification of PDGFRA (4q12), CCND3 (6p21), EGFR (7p12), CDK4 (12q14) and/or MDM2 (12q14.3–q15), and AKT1 (14q32.3) in the respective tumors. Separate analysis of the gliomatous and sarcomatous components of eight gliosarcomas by CGH after microdissection and universal DNA amplification revealed that both components shared 57% of the chromosomal imbalances detected. Taken together, our data indicate that the genomic changes in gliosarcomas closely resemble those found in glioblastomas. However, the number of chromosomes involved in imbalances in gliosarcomas was significantly lower than that in glioblastomas, indicating a higher genomic stability in gliosarcomas. In addition, we provide further support for the hypothesis that the gliomatous and sarcomatous components are derived from a single precursor cell clone, which progressed into subclones with distinct morphological features during tumor evolution. According to our data, gain/amplification of genes on proximal 12q may facilitate the development of a sarcomatous phenotype. © 2002 Wiley‐Liss, Inc.
Differential expression of multiple isoforms of the ELKS mRNAs involved in a papillary thyroid carcinoma
Authors: Nakata Tomoko , Yokota Takashi , Emi Mitsuru , Minami Shiro
Published: October 2002

A novel gene, ELKS, whose 5′ portion was fused to the RET gene, was found in a papillary thyroid carcinoma. A cDNA of this gene obtained from a human‐brain cDNA library revealed that it encoded a peptide of 948 amino acids, termed ELKSα. We identified four other isoforms, which encoded ELKSβ, ELKSγ, ELKSδ, and ELKSϵ proteins consisting, respectively, of 992, 720, 1088, and 1116 amino acid residues. Analysis of the gene structure revealed that the isoforms were generated by alternative splicing. Isoforms β, γ, δ, and ϵ all contain an optional exon (exon14a), but ELKSγ, ‐δ, and ‐ϵ lack exon 1b. ELKSγ lacks exons 3 to 6. ELKSδ and ‐ϵ lack exons 12 and 17; ELKSϵ contains an optional exon (exon 6a). Analysis by RT‐PCR suggested that ELKSα and ELKSβ mRNAs are abundant in the brain, ELKSδ and ELKSϵ mRNAs predominate in testis and thyroid, and ELKSϵ mRNA predominates in other tissues. To prove whether the fusion of different ELKS isoforms to RET (between ELKS coiled‐coil domains and the RET kinase domain) could produce chimeric proteins that could be autophosphorylated, we synthesized ELKSγ‐RET, ELKSδ‐RET, and ELKSϵ‐RET fusion proteins in vitro. Immunoblotting with anti‐ELKS, anti‐RET, and anti‐phosphotyrosine antibodies demonstrated that the chimeric proteins were constitutively phosphorylated at tyrosine residues, whereas native RET protein was not. These results indicate that the ELKS gene is alternatively spliced, and that every type of ELKS‐RET chimeric protein having oligomerization domains can activate RET's cytoplasmic tyrosine kinase. © 2002 Wiley‐Liss, Inc.
Axes establishment during eye morphogenesis in Xenopus by coordinate and antagonistic actions of BMP4, Shh, and RA
Authors: Sasagawa Satoru , Takabatake Takashi , Takabatake Yuka , Muramatsu Tatsuo , Takeshima Kazuhito
Published: October 2002

Summary: We have examined the roles of BMP4, Shh, and retinoic acid in establishing the proximal‐distal and dorsal‐ventral axes in the developing Xenopus eye. Misexpression of BMP4 caused the absence of an optic stalk and the expansion of dorsal and distal markers, tbx2/3/5, and pax6, at the expense of ventral and proximal markers vax2 and pax2. When Shh or Noggin, an antagonist of BMPs, was misexpressed, the reverse expression patterns of these marker genes were observed. These results suggest that BMP4 is involved in the specification of not only dorsal in the optic cup but also distal in the optic vesicle. Because Shh did not suppress bmp4 expression, unlike Noggin, Shh and BMP4 may antagonistically regulate common downstream genes in developing eye. We also found the difference between the effects of Shh and retinoic acid, another possible ventralizing factor, suggesting that Shh could promote ventralization independently of retinoic acid. These findings provide important clues to the coordinate and antagonistic actions of BMP4, Shh, and retinoic acid in axes specifications of Xenopus eyes. genesis 33:86–96, 2002. © 2002 Wiley‐Liss, Inc.
A human CD2 minigene directs CRE‐mediated recombination in T cells in vivo
Authors: Wilson Trevor J. , Cowdery Helen E. , Xu Dakang , Kola Ismail , Hertzog Paul J.
Published: October 2002

Summary: We have produced a mouse line that expresses the Cre recombinase under the regulation of a human CD2 minigene to facilitate Cre‐specific recombination in T lymphocytes. These mice express Cre in thymocytes and T cells and are capable of efficient site‐specific recombination as shown in the spleen and thymus, but not other tissues. These mice thus provide an excellent resource for the study of gene function during thymocyte development and in mature T cells. genesis 33:181–184, 2002. © 2002 Wiley‐Liss, Inc.
Mantel statistics to correlate gene expression levels from microarrays with clinical covariates
Authors: Shannon William D. , Watson Mark A. , Perry Arie , Rich Keith
Published: October 2002

Mantel statistics provide an additional step to standard approaches in the analysis of gene expression and covariate data, allow the calculation of standard statistics such as correlation, partial correlation, and regression coefficients, and, with permutation tests, provide P values for these statistics to relate the sample covariates to the expression levels. In this article we describe the Mantel statistics and illustrate their use and interpretation with data from a study of seven human oligodendrogliomas (brain tumors) where expression levels of 1,013 genes and five covariates were previously analyzed using standard approaches. In the previous analysis of these data, qualitative relationships were found between gene expressions and two of the clinical covariates. We show in this article how the Mantel statistics are able to formally quantify and provide P values to determine statistical significance of these relationships. We also show how the Mantel statistics can be used to rank subsets of genes, found using standard clustering methods, in terms of differential expression across samples. Genet. Epidemiol. 23:87–96, 2002. © 2002 Wiley‐Liss, Inc.
Role of gene expression microarray analysis in finding complex disease genes
Authors: Gu Chi C. , Rao D.C. , Stormo Gary , Hicks Chindo , Province Michael A.
Published: October 2002

The promise of gene expression studies using microarray technology has inspired much new hope for finding complex diseases genes. It has become clear that complex diseases result from collective actions of many genetic and nongenetic factors. Therefore, genetic dissection of complex diseases should be carried out in a global context. The technology of gene expression microarray analysis (GEMA) can provide such global information on transcription activities of essentially all genes simultaneously. It is hoped that this promising technology can be applied to samples drawn from large‐scale, well‐defined genetic epidemiological studies and help us untangle the web of pathways leading to complex diseases. However, extremely noisy GEMA data pose serious challenges in terms of the statistical methodologies needed. Extensive work is needed in order to respond to the challenges before one can fully utilize the potential power provided by GEMA. We begin in this paper by identifying several statistical problems related to the application of GEMA to genetic epidemiological analysis, and consider study designs that might benefit from this promising new technology. While it is still too early to tell how much of the enormous potential of GEMA will be realized ultimately, its success will probably depend most critically on the ability of statistical genetics to rise to the challenge of mining information from a sea of noise. Genet. Epidemiol. 23:37–56, 2002. © 2002 Wiley‐Liss, Inc.
Depositional environment and sequence architecture of the Silurian Coralliferous Group, Southern Pembrokeshire, UK
Authors: Hillier Robert D.
Published: October 2002

The Lower Silurian siliciclastic Coralliferous Group is shown to have been deposited in an intra‐shelf position 10–15 km south of the palaeogeographic shelf‐break of the Welsh Basin. After a phase of thermal subsidence related to the development of the predominantly Llandovery Skomer Volcanic Group, the shelf basin was transgressed. This transgression was punctuated by an episode of tectonic uplift in southern Pembrokeshire, resulting in subaerial exposure of the shelf and a significant basinward shift in sedimentary environments. Erosion and sediment bypass ensued, with coarse‐grained low‐sinuosity fluvial channels transporting sediment to the northerly Welsh Basin, where significant submarine fans developed. During the early Telychian, renewed transgression took place, with lowstand gravels being ravined and reworked into parasequences of the transgressive systems tract. These thin, coarse‐grained parasequences record deposition within high‐energy wave‐dominated shoreface/inner shelf environments. Further coastal onlap resulted in the closing down of significant coarse‐grained sediment supply, with the remaining Coralliferous Group being dominated by wave‐influenced silts, mud‐shales and thin sandstones comprising the highstand systems tract. Copyright © 2002 John Wiley & Sons, Ltd.
Glial induction of blood‐brain barrier‐Like L‐system amino acid transport in the ECV304 cell line
Authors: Chishty M. , Reichel A. , Begley D.J. , Abbott N.J.
Published: October 2002

The blood‐brain barrier (BBB) is formed by the presence of tight junction complexes between brain endothelial cells that restrict paracellular permeability. As a consequence, a number of transport proteins are expressed on cerebral endothelial cells to facilitate the transport of nutrients into the brain. Although the modulation of barrier tight junction properties by glial‐conditioned medium and by second messengers is well established, little is known about the effects of these factors on carrier‐mediated BBB transport processes. The ECV304 cell line shows an endothelial phenotype and can be induced to upregulate certain BBB features in the presence of glial factors. In the present study, we have examined the effect of conditioned medium derived from rat C6‐glioma cells (C6CM) on the function of the L‐system amino acid transporter in ECV304 cells, using L‐leucine as the model substrate, and have determined whether the changes observed can be mimicked by modulating intracellular cAMP levels. ECV304 cells exposed to C6CM exhibited a significant increase in both the affinity of leucine transport and the diffusional constant (Michaelis‐Menten), while the maximal transport capacity remained unchanged. Conversely, acute exposure to modulators of the PKA and PKC second messenger pathways was found to reduce significantly the maximal transport capacity and diffusion constants, while transport affinity remained unchanged. In both cases, the maximal flux of leucine was increased, indicating transport of greater efficiency. This study indicates that exposure of ECV304 cells to C6CM provides an influence inducing L‐system transport properties characteristic of brain endothelial cells. Furthermore, it appears that L‐system‐mediated transport of amino acids can be modulated by several distinct pathways. GLIA 39:99–104, 2002. © 2002 Wiley‐Liss, Inc.
GM‐CSF and M‐CSF modulate β‐chemokine and HIV‐1 expression in microglia
Authors: Si Qiusheng , Cosenza Melissa , Zhao Meng‐Liang , Goldstein Harris , Lee Sunhee C.
Published: October 2002

Significant numbers of patients with acquired immunodeficiency syndrome (AIDS) develop CNS infection primarily in macrophages and microglial cells. Therefore, the regulation of human immunodeficiency virus type 1 (HIV‐1) infection and activation of the brain mononuclear phagocytes subsequent to infection are important areas of investigation. In the current report, we studied the role of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and macrophage‐CSF (M‐CSF) in the expression of antiviral β‐chemokines and HIV‐1 p24 in cultures of primary human fetal microglia. We found that stimulation with GM‐CSF or M‐CSF induced macrophage inflammatory proteins (MIP‐1α and MIP‐1β) and augmented RANTES expression, after HIV‐1 infection of microglia. This was not due to the effect of GM‐CSF on viral expression because GM‐CSF was neither necessary nor stimulatory for viral infection, nor did GM‐CSF enhance the expression of env‐pseudotyped reporter viruses. Blocking GM‐CSF‐induced microglial proliferation by nocodazole had no effect on β‐chemokine or p24 expression. The functional significance of the GM‐CSF‐induced β‐chemokines was suggested by the finding that, in the presence of GM‐CSF, exogenous β‐chemokines lost their anti‐HIV‐1 effects. We further show that although HIV‐1‐infected microglia produced M‐CSF, they failed to produce GM‐CSF. In vivo, GM‐CSF expression was localized to activated astrocytes and some inflammatory cells in HIV‐1 encephalitis, suggesting paracrine activation of microglia through GM‐CSF. Our results demonstrate a complex interplay between CSFs, chemokines, and virus in microglial cells and may have bearing on the interpretation of data derived in vivo and in vitro. GLIA 39:174–183, 2002. © 2002 Wiley‐Liss, Inc.
The second Leicester survey of memory clinics in the British Isles
Authors: Lindesay James , Marudkar Mangesh , van Diepen Erik , Wilcock Gordon
Published: October 2002

Background

The number of memory clinics in the British Isles has increased since our first survey in 1993.

Objectives

The aim of this survey was to determine the memory clinics' characteristics and functions, and to compare these with the findings of our previous survey.

Methods

An expanded version of the 1993 questionnaire was sent to 102 possible memory clinics, identified by various means. There were 72 replies, 58 of which were from currently active clinics.

Results

There has been a substantial growth in the number of clinics since our previous survey in 1993, apparently stimulated by the licensing of cholinesterase inhibitor durgs for Alzheimer's disease (AD) and the development of services for early‐onset dementia. Most of the new memory clinics have been set up within NHS old age psychiatry services, and they tend to be smaller and have less of an academic focus than the older clinics. However, they are similar in many aspects of their functioning, and have a similar range of practice with regard to patient assessment.

Conclusions

As memory clinics move out from academic centres into mainstream clinical services, there is potential for greater co‐ordination of their activities, and the development of an agreed core data set for assessment that would be valuable in the national monitoring of new anti‐dementia treatments in clinical practice. Copyright © 2002 John Wiley & Sons, Ltd.
The psychosocial burden on spouses of the elderly with stroke, dementia and Parkinson's disease
Authors: Thommessen Bente , Aarsland Dag , Braekhus Anne , Oksengaard Anne Rita , Engedal Knut , Laake Knut
Published: October 2002

Objective

To characterize the psychosocial burden on spouses living with the elderly suffering from mild dementia, stroke and Parkinson's disease, and to identify patient characteristics associated with it.

Materials and methods

Data on patient—spouse couples came from three studies of patients with stroke (36 couples), mild dementia (92 couples) and Parkinson's disease (58 couples). The psychosocial burden was recorded by the 15—item Relatives' Stress Scale (RSS). A factor analysis of this instrument produced a one‐factor solution (CFI = 0.98) consisting of eight items with good face validity and acceptable reliability within each diagnostic group (Cronbach's alpha range 0.66–0.69). Covariates of this factor were identified using structural equation modeling (SEM) by regression on patient's age, gender, cognitive function (MMSE), activities of daily living (ADL) and depressive symptoms (MADRS).

Results

Disorganization of household routines, difficulties with going away for holidays, restrictions on social life, and the disturbances of sleep were the most frequently reported problems in all three groups. According to the mean sumscore on the RSS, the perceived psychosocial burden was similar across the diagnostic groups. In the final SEM model, a lower cognitive function of the patient was associated with a higher psychosocial burden on the spouses of patients with stroke (β = −1.3, p = 0.01) and Parkinson's disease (β = −0.89, p < 0.01), while in the dementia group, only an insignificant trend was demonstrated. In the dementia group, a significantly higher burden was identified on female spouses (β = −0.56, p = 0.04). A heavier burden of care was also associated with depressive symptoms in the patients with Parkinson's disease. In neither group did the final model disclose any effect of ADL function on the spouse's psychosocial burden.

Conclusion

Spouses caring for patients with dementia, stroke and Parkinson's disease perceive a similar type and level of psychosocial burden, independent of the disease. The cognitive functioning of the patient is a particularly important factor in this, especially when caring for patients with stroke or Parkinson's disease. Copyright © 2002 John Wiley & Sons, Ltd.
Mild extrapyramidal signs and functional impairment in ageing
Authors: Richards Marcus , Touchon Jacques , Ledesert Bernard , Ritchie Karen
Published: October 2002

Background

Little is known about the clinical significance of mild extrapyramidal signs (EPS) in elderly individuals. We investigated whether EPS are associated with functional impairment in older people with cognitive decline.

Methods

A sub‐group of 105 participants from the EUGERIA Study of Cognitive Ageing without Parkinson's disease or dementia, but with informant evidence of cognitive decline, were followed across three years and underwent neurological examination and assessment of mental health, cognition and functional capacity.

Results

28.6% had at least one EPS (resting tremor, muscular rigidity or akinesia, of which rigidity was the most frequent). EPS presence was significantly associated with functional impairment after controlling for age and cognitive impairment (AAMI), although the association was reduced to borderline significance after further adjustment for depression and psychotropic medication use. There was evidence of colinearity between EPS and depression, possibly suggesting similar underlying mechanisms.

Conclusions

There is an association between mild EPS and functional impairment in older persons with evidence of cognitive decline, but free of dementia or Parkinson's disease. Copyright © 2002 John Wiley & Sons, Ltd.
Does the HoNOS 65+ meet the criteria for a clinical outcome indicator for mental health services for older people?
Authors: Spear Jon , Chawla Sudarshan , O'Reilly Maria , Rock Daniel
Published: October 2002

Background

A clinical indicator should demonstrate clinically meaningful change, be relevant, allow comparisons between services, be acceptable to clinicians, and have acceptable validity, reliability and sensitivity to change. The HoNOS 65+ has been suggested as a clinical outcome indicator. The sensitivity to change of the HoNOS 65+ is not known.

Methods

This is a prospective study using routine clinical data. A pilot cohort (n = 42) was used to measure the concurrent validity of the HoNOS 65+ with the Mini‐Mental State Examination (MMSE), Geriatric Depression Scale (GDS‐15) and Brief Agitation Rating Scale (BARS). The main cohort of 245 consecutive referrals to a community mental health service for older adults was used to assess sensitivity to change against the CIBIC+.

Results

The HoNOS 65+ was acceptable to case managers, most HoNOS 65+ items had excellent interrater reliability and the HoNOS 65+ had good concurrent validity. Changes in the HoNOS 65+ scores between assessment and discharge had a moderate, but significant correlation with CIBIC+ scores.

Conclusion

The HoNOS 65+ meets the criteria for a clinical outcome indicator for community mental health services for older people. The HoNOS 65+ is sensitive to change. Copyright © 2002 John Wiley & Sons, Ltd.
The prevalence, diagnosis and treatment of depression in dementia patients in chronic care facilities in the last six months of life
Authors: Evers Martin M. , Samuels Steven C. , Lantz Melinda , Khan Khalid , Brickman Adam M. , Marin Deborah B.
Published: October 2002

Objective

To assess the prevalence, diagnosis and treatment of depression among dementia patients and normal controls in chronic care facilities in the last six months of life.

Method

We reviewed perimortal data concerning dementia severity, depressive symptoms and diagnoses, and medication use for 279 dementia patients and 24 normal controls brought to autopsy through an Alzheimer's Disease Resource Center.

Results

Major depression was highly prevalent among both dementia patients and normal controls in chronic care facilities in the last six months of life. This depression was under‐diagnosed by physicians. Documentation of depressive symptoms by medical support staff has improved over time. However, physician diagnosis of depression has not improved. Recognition of depression was significantly lower for patients with severe dementia. Depression was under‐treated in both dementia patients and normal controls, although treatment rates may be increasing. Anxiolytics and hypnotics were often used in lieu of, or in addition to, antidepressant therapy.

Conclusions

Major depression was highly prevalent in both dementia patients and normal controls, indicating that depression is an important issue for the elderly in the last six months of life irrespective of cognitive status. Under‐diagnosis of depression may be an important clinical issue. As physician diagnosis of depression has not improved with time, further physician training and/or awareness initiatives may be warranted. Depression, a treatable cause of excess morbidity and mortality, was undertreated in all groups studied. However, treatment rates may be improving. The prevalent use of anxiolytics and hypnotics for depressed patients is problematic. Copyright © 2002 John Wiley & Sons, Ltd.
Gender, aggression and serotonergic function are associated with response to sertraline for behavioral disturbances in Alzheimer's disease
Authors: Lanctôt Krista L. , Herrmann Nathan , van Reekum Robert , Eryavec Goran , Naranjo Claudio A.
Published: October 2002

Background

Indications for serotonergic medications in the treatment of behavioral disorders associated with Alzheimer's disease (AD) remain to be established.

Method

Sertraline (100 mg OD) was evaluated in a double‐blind, randomized, placebo‐controlled cross‐over study in 22 nondepressed patients with severe probable AD and significant behavioral disturbance. Each subject was given a fenfluramine challenge to evaluate central serotonergic tone.

Results

Eight of 21 (38%) completers responded to sertraline. Drug responsive behaviors included aggression/agitation, irritability and aberrant motor behavior. Low aggression, female gender and large prolactin increase were associated with a better response. There was a trend for decreased aggression during sertraline versus placebo (p = 0.08).

Conclusion

Aggression, gender and serotonergic function were associated with sertraline response. Larger randomized controlled trials are needed to clarify the profile of responders. Copyright © 2002 John Wiley & Sons, Ltd.
Cross‐cultural comparison of the Mini‐Mental State Examination in United Kingdom and United States participants with Alzheimer's disease
Authors: Gibbons Laura E. , van Belle Gerald , Yang Minhua , Gill Caroline , Brayne Carol , Huppert Felicia A. , Paykel Eugene , Larson Eric
Published: October 2002

Objectives

The relative difficulties of items on the Mini‐Mental State Examination (MMSE) were compared in English‐speaking Alzheimer's disease (AD) patients in the United States (US) and United Kingdom (UK).

Methods

Participants were aged 75 and over, with a clinical diagnosis of AD according to standardized methods. Initial MMSE scores from an AD patient registry in the US (n = 401), and a field survey in the UK (n = 139) were compared. Item Characteristic Curve analysis (ICC) was used to calculate the relative difficulty of individual MMSE items, adjusted for the remaining MMSE items. Age, gender, education, and severity of disease were evaluated as possible confounders.

Results

UK participants found it relatively more difficult to name their county than US participants did to name their state. The relative difficulties of registration and recall, repeating a phrase, and following verbal directions also were significantly higher for the UK participants, even after adjustment for other factors.

Conclusions

Differences between the cohorts could be explained by translation artifacts in the test items or by cultural differences in the manifestation of AD. In this study, most, if not all differences can be explained by the former. ICC analysis can be used to develop tests that are functionally equivalent, a prerequisite for comparing dementia in different populations. Copyright © 2002 John Wiley & Sons, Ltd.