bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin resistance in type 1 diabetes
Authors: Greenbaum Carla J.
Published: October 2002

Insulin resistance plays a larger role in the type 1 diabetes disease process than is commonly recognized. The onset of type 1 diabetes is often heralded by an antecedent illness and/or the onset of puberty, both conditions associated with insulin resistance. In the face of a damaged β‐cell and thus reduced insulin secretion, this change is enough to manifest hyperglycemia. During the first year of clinical disease, considerable evidence suggests that the occurrence of clinical remission or ‘honeymoon period’ is due to a temporary resolution of the insulin‐resistant state present at diagnosis. Intensive diabetes management is associated with both improved insulin sensitivity and β‐cell function. This indicates that the historical data on the changes in insulin secretion post‐diagnosis may be inappropriate when designing current studies. The known physiological relationship between β‐cell function and insulin sensitivity complicates interpretation of insulin secretion data obtained as part of prevention or intervention trials. While it is recommended that at least a subset of subjects participating in these trials undergo formal measurements of insulin sensitivity to evaluate effects of therapy on this parameter independent of effects on the β‐cell, the sample size must be sufficient to determine an effect if present. Finally, one could speculate that it is possible that subsets of people with mild manifestations of the type 1 autoimmune disease process could benefit from treatments aimed at improving the insulin‐resistant state. Copyright © 2002 John Wiley & Sons, Ltd.
Regulation of cadherin junctions during mouse submandibular gland development
Authors: Menko A. Sue , Zhang Liping , Schiano Frank , Kreidberg Jordan A. , Kukuruzinska Maria A.
Published: October 2002

Submandibular gland (SMG) development involves branching morphogenesis of the salivary epithelium into the surrounding mesenchyme, accompanied by proliferation and differentiation of immature salivary cells along acinar and ductal cell lineages. During development, salivary cell sorting and cell–cell adhesion are likely to be directed by cadherin adhesion receptors. We show that two classic cadherins, N‐ and E‐cadherin, participate in SMG development. Early in embryonic morphogenesis, both cadherins displayed diffuse staining with regionalized localization to cell–cell borders. At this stage, significant pools of N‐ and E‐cadherins were Triton‐soluble, suggesting that fractions of these molecules were not localized to stable junctional complexes associated with the actin cytoskeleton. With cytodifferentiation, cadherins became progressively Triton‐insoluble, and this correlated with their organization at cell–cell interfaces. In the cytodifferentiated SMG, N‐cadherin was absent, whereas E‐cadherin remained at cell–cell interfaces. Early in morphogenesis, β‐catenin was also primarily Triton‐soluble, and its association with the actin cytoskeleton and localization to the adherens junctions increased with cytodifferentiation. Greater recruitment of cadherins and β‐catenin to cell–cell borders was paralleled by changes in membrane association of two Rho GTPases, Cdc42 and RhoA. N‐cadherin was detected only at early stages of postnatal development, whereas E‐cadherin and β‐catenin became progressively Triton‐insoluble during differentiation. Our results indicate that N‐cadherin functions transiently in SMG development. On the other hand, E‐cadherin and β‐catenin appear to play different roles during tissue organization and cytodifferentiation. In early morphogenesis, E‐cadherin and β‐catenin are likely to participate in SMG remodeling, whereas during cytodifferentiation, they form stable cell–cell contacts, and may collaborate with Rho GTPases in the establishment and maintenance of salivary cell polarity. © 2002 Wiley‐Liss, Inc.
Craniofacial abnormalities resulting from targeted disruption of the murine Sim2 gene
Authors: Shamblott M.J. , Bugg E.M. , Lawler A.M. , Gearhart J.D.
Published: October 2002

Sim2 is a member of the basic helix‐loop‐helix PAS transcription factor gene family and is evolutionarily related to the Drosophila single‐minded gene, a key regulator of central nervous system midline development. In an effort to determine the biological roles of Sim2 in mammalian development, we disrupted the murine Sim2 gene through gene targeting. Mice homozygous for the disrupted allele (Sim2 ‐/‐) exhibit a cleft of the secondary palate and malformations of the tongue and pterygoid processes of the sphenoid bone. These craniofacial malformations are the most probable cause of aerophagia (air swallowing with subsequent accumulation of air in the gastrointestinal tract) and postnatal death exhibited by Sim2 ‐/‐ mice. The developing palates of the Sim2 ‐/‐ mice are hypocellular, and at embryonic day 14.5 contain excess extracellular matrix component hyaluronan (HA) compared with heterozygotes and homozygous wild‐type littermates. HA plays an important role in the regulation and mechanics of palate development. Its premature accumulation in Sim2 ‐/‐ animal palates suggests a regulatory role for Sim2 in HA synthesis and in the establishment of craniofacial architecture. © 2002 Wiley‐Liss, Inc.
Expression of the ankyrin repeat domain 6 gene (Ankrd6) during mouse brain development
Authors: Tissir F. , Bar I. , Goffinet A.M. , Lambert De Rouvroit C.
Published: October 2002

The structure and developmental expression pattern of the ankyrin repeat domain 6 (Ankrd6) gene, initially named Diversin, were studied in the mouse. Ankrd6 is transcribed as a 5.8‐kb mRNA composed of 15 exons that encodes a 712 amino acid protein with 6 ankyrin repeats. Ankrd6 is expressed prominently in the developing brain from E12 to maturity, suggesting a role during brain development. In embryos, expression is maximal in ventricular zones of neuronal proliferation and intermediate zones of neuronal migration and extends to postmigratory neuronal fields during the postnatal period. In the mature brain, the Ankrd6‐related signal is highest in cortical layer II, granule cells of the dentate gyrus, olfactory granules and a subset of Purkinje cells in the vestibulocerebellum. Ankrd6 is related to the Drosophila gene Diego, which interacts with Flamingo in the regulation of planar cell polarity (Feiguin et al., 2001). However, the canvas of Ankrd6 expression does not match closely that of the three mouse Flamingo homologs, Celsr1–3 (Tissir et al., 2002). These data suggest that Ankrd6 may be involved in brain development in interaction with Celsr/Flamingo but also other signaling pathways. © 2002 Wiley‐Liss, Inc.
A large‐scale survey of eating disorder symptomatology among female adolescents in the People's Republic of China
Authors: Huon Gail F. , Mingyi Qian , Oliver Kylie , Xiao Guanglan
Published: October 2002

Objectives

This study was designed to document comprehensively the prevalence of the signs, symptoms, and associated features of anorexia nervosa and bulimia nervosa among schoolgirls in the People's Republic of China.

Methods

Female participants were recruited from both junior and senior high schools with varying levels of academic performance in six cities (Beijing, Shanghai, Guangzhou, Zunyi, Xin Xiang, and Yinchuan) that are representative of different geographical regions in China (North East, Central East, South East, South West, North West, and North). In each school, girls were recruited across all grades, in order to cover ages 12–19 years. The final sample comprised 1,246 participants whose mean age was 15.76 years. The questionnaire, developed specifically for the purpose of this research, assessed the diagnostic criteria and associated features of anorexia nervosa and bulimia nervosa outlined in the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders.

Results and Discussion

Our results have shown a surprisingly high level of weight‐related concerns among schoolgirls across mainland China. There would seem to be few cases of anorexia or bulimia, although some girls satisfy criteria for partial diagnoses. Our findings highlight the difficulty of identifying girls who are underweight, at least by applying the standard Western procedure for categorizing body mass index. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 32: 192–205, 2002.
An all‐solid‐state pulsed power generator using a high‐speed gate‐turn‐off thyristor and a saturable transformer
Authors: Sakugawa Takashi , Akiyama Hidenori
Published: October 2002

Recently, high‐repetition‐rate pulsed power generators using a magnetic pulse compression circuit (MPC) and semiconductor switches have been developed. We have developed a new all‐solid‐state pulsed power generator for use with a high‐repetition‐rate excimer laser and in an ozonizer. The all‐solid‐state generator consists of a semiconductor switch and an MPC with saturable inductors (SI) and a saturable transformer (ST). The semiconductor switch is a high‐speed gate‐turn‐off (GTO) thyristor. The switching speed of the GTO thyristor was improved, decreasing the switching loss. The ST with an Fe‐based nanocrystalline magnetic core has two functions, those of step‐up transformer and magnetic switch. The high‐speed GTO thyristor and the new MPC can be used to realize a high‐performance, simple all‐solid‐state pulsed power generator. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 140(4): 17–26, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.2006
A study of robust generation mix under uncertain environments
Authors: Yasuda Keiichiro , Tsunematsu Mitsuaki , Watanabe Takao
Published: October 2002

In recent years, the trend has been toward factors (e.g., demand for load, energy cost) becoming more and more uncertain in power system expansion planning. Thus, it has become necessary to take this uncertainty into account in determining generation plans. In this paper, a robust generation plan is defined explicitly as a plan that ensures fixed performance (economy) despite deviations in these factors. In addition, a new formulation of the robust generation mix problem, whose purpose is to determine the most robust combination of plants in a target year, is proposed. It is generally difficult to solve the formulated problem with parameters. However, by analyzing a proposed formulation from the viewpoint of optimization, we show that the proposed formulation is transformed into the conventional optimization problem without parameters. The simulation results on a typical model show that the generation mix produced by the proposed formulation is more robust than that produced by the conventional formulation. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(1): 26–35, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.2009
The similarity–attraction relationship revisited: divergence between the affective and behavioral facets of attraction
Authors: Michinov Estelle , Monteil Jean‐Marc
Published: October 2002

In contemporary attitudes‐and‐attraction research, attraction has been viewed as a multidimensional construct. Moreover, the effects of dissimilar and similar attitudes have been shown to vary with the facets of attraction measured. The hypotheses tested are that (1) only the proportion of similar attitudes relevant to the social context or interaction goals affects behavioral attraction (i.e. interpersonal distance between the participant and targets), and (2) the proportion of similar attitudes influences affective attraction (i.e. Byrne's attraction measure), regardless of attitude relevance. Two experiments were conducted with classroom activities (Experiment 1) and a writing workshop (Experiment 2) as the social contexts. The results of both experiments supported the hypotheses. Clearly, a solely affective measure of attraction seems inadequate for understanding the similarity–attraction relationship. Copyright © 2002 John Wiley & Sons, Ltd.
Culture, gender and self–close‐other(s) connectedness in Canadian and Chinese samples
Authors: Li Han Z.
Published: October 2002

Founded upon the theories of Independent–Interdependent Self‐Construal and I–C, the main goal of this study was to test, via an adapted IOS Scale, whether Anglo‐Canadians were more independent than Mainland Chinese in construing their relationship with family members and friends. Strong cultural differences were found in self–family connectedness, but not in self–friends connectedness. Chinese were closer to their family members than Canadians, but Canadians were as close to their friends as Chinese. In both samples, gender difference was found in self–friends connectedness, but not in self–family connectedness. In the Canadian sample, females were closer to their friends than males, while in the Chinese sample, males were closer to their friends than females. In conclusion, this study contributes to the field in three ways. First, the finding that Canadians are as connected as Chinese to their close friends unprecedentedly contests one fundamental assumption of the theories of independent‐interdependent self‐construal (Markus & Kitayama, 1991) and I–C (Hofstede,1980; Triandis, Bontempo, Villareal, Asia & Lucca, 1988) that individualists (e.g. Anglo‐Canadians) are more independent than collectivists (e.g. Chinese) on all dimensions of human relations. Second, the proposition (Cross & Madson, 1997) that Western males and females differ in the same way individualists and collectivists differ in their self‐construal is not supported. Finally, the adaptation of the IOS Scale proposes a refreshing direction in cross‐cultural research. Graphic representations may be less susceptible to cross‐cultural misconstrual than verbal statements since the former involves little or no translation from one language to another. Copyright © 2002 John Wiley & Sons, Ltd.
Mutant frequency and mutational spectra in the Tk and Hprt genes of N‐ethyl‐N‐nitrosourea‐treated mouse lymphoma cells†
Authors: Chen Tao , Harrington‐Brock Karen , Moore Martha M.
Published: October 2002

The mouse lymphoma assay (MLA) utilizing the Tk gene is widely used to identify chemical mutagens. The autosomal location of the Tk gene allows for the detection of a wide range of mutational events, from point mutations to chromosome alterations. However, chemically induced point mutation spectra in the Tk gene of mouse lymphoma cells have not been characterized. In this study, we determined and compared the mutagenicity and mutational spectra of N‐ethyl‐N‐nitrosourea (ENU) in the Tk and Hprt genes of mouse lymphoma cells. Treatment of L5178Y mouse lymphoma cells with 100 μg/ml ENU induced a Tk mutant frequency of 756 × 10−6 and an Hprt mutant frequency of 311 × 10−6. Sequence analysis of Tk and Hprt mutant cDNAs showed a similar overall mutation pattern in the two genes with base‐pair substitutions accounting for 83% of non–loss of heterozygosity mutations in the Tk gene and 75% of all mutations in the Hprt gene. The most common point mutation induced by ENU was G:C → A:T transition (36 and 28% of independent mutations detected in the Tk and Hprt genes, respectively). The mutation spectra induced by ENU in both the Tk and Hprt genes were different from the respective patterns produced in mutants from untreated cells. About 9% of Tk and 7% of Hprt mutations from control cells were in‐frame deletions, whereas no such mutations were found among the ENU‐induced Tk and Hprt mutations. Our results indicate that ENU produces a chemical‐specific point mutational profile in the Tk gene of mouse lymphoma cells that is remarkably similar to that found in the X‐linked Hprt gene. This study provides evidence that the MLA can be used not only to detect point mutagens but also for analysis of mutational spectra. Environ. Mol. Mutagen. 39:296–305, 2002. Published 2002 Wiley‐Liss, Inc.
A preliminary description of the use of ‘Relapse Management Cards’ in anorexia nervosa
Authors: Page Lisa A. , Sutherby Kim , Treasure Janet L.
Published: October 2002

This paper describes the preliminary and novel use of ‘Relapse Management Cards’ in a group of inpatients with a diagnosis of Anorexia Nervosa. During the study period, 41 patients completed ‘Relapse Management Cards’ during facilitated family meetings. The patient generated the information contained in the card. Cross‐sectional analysis of the data contained in the cards provides information on plans to prevent relapse, signs of relapse and plans in the event of relapse. Certain parts of the ‘Relapse Management Cards’ were more frequently completed than other parts. Early experience suggests that ‘Relapse Management Cards’ may be an effective way of eliciting patients' ideas on care after discharge. There is increasing interest in the use of advance directives in psychiatry to which the ‘Relapse Management Card’ has relevance. Copyright © 2002 John Wiley & Sons, Ltd and Eating Disorders Association.
Relations between morphology, air flow, sand flux and particle size on transverse dunes, Taklimakan Sand Sea, China
Authors: Wang Xunming , Dong Zhibao , Zhang Jiawu , Zhao Aiguo
Published: October 2002

Field experiments on two isolated transverse dunes with different scales in the Taklimakan Sand Sea show that particle size and slope control the threshold shear velocity and sand flows on the stoss of the dunes. The decreased threshold shear velocity and the unsaturated sand flows are the main reasons why sands are not deposited at the toe of the dunes. The particle size controls sand flux through its influence on the aerodynamic roughness elements and threshold shear velocities. The sand flux is different for dune surfaces with different particle size distributions. Under the control of the medium to low stress of the drifting‐sand winds, the results of the field experiments and particle size analysis showed that sand transport had little influence on the particle size distributions. The mean particle size being transported on the stoss is lower than that on the dune surface. It is difficult to determine whether or not the wind is fully saturated with sands when sand flux calculation is mainly dependent on the shear velocity and the mean particle size. The sands within some range of the particle size are transported and developed into simple transverse dunes, and then the interdune surface is coarsened and alternated with the draas in the Taklimakan Sand Sea. Copyright © 2002 John Wiley & Sons, Ltd.
In‐situ gamma‐ray spectrometric study of weathered volcanic rocks in Hong Kong
Authors: Chen Margie Q. F. , Chan Lung S.
Published: October 2002

In‐situ gamma‐ray spectrometry (GRS) measurements were conducted at 35 sites in Hong Kong where volcanic rocks with varying extent of weathering were exposed. Elemental analyses using X‐ray fluorescence spectrometry and inductively coupled plasma–mass spectrometry were carried out on samples collected from these 35 plus 22 other locations to assess the feasibility of using the GRS method to quantify the extent of weathering. The Parker weathering index, varying within a range of 0·0–0·8 for the samples studied, was used as a geochemically based reference scheme for correlating the gamma‐ray spectrometric results with the extent of weathering. For the former 35 sites, the concentrations of the three major radioelements, K, U and Th, determined by in‐situ GRS were compared to laboratory‐determined values from the samples. The study reveals that no significant change occurs to the contents of the three radioelements during the initial state of weathering. But once the rocks become highly weathered, further progression of weathering is accompanied by a systematic removal of K and an increased dispersion of U and Th. The results show that K content, which is indicative of the extent of weathering, can be retrieved reliably with the gamma‐ray spectrometry technique. The study has given support to the potential use of the downhole spectral gamma method for evaluation of weathering grade and the detection of subsurface clay‐rich levels. Copyright © 2002 John Wiley & Sons, Ltd.
Lessons learned about science and participation from multisite evaluations
Authors: Leff H. Stephen , Mulkern Virginia
Published: October 2002

Publicly funded multisite evaluations should help bring safe, effective interventions to the mental health and substance abuse treatment fields. Two principles, science‐based practice and stakeholder participation, drive multisite evaluations of behavioral interventions. We examine the roles of these principles in the five programs described in this volume and draw lessons for future studies.
Eocene primates from Myanmar: Historical perspectives on the origin of Anthropoidea
Authors: Ciochon Russell L. , Gunnell Gregg F.
Published: October 2002

The phylogenetic and geographic origins of the primate suborder Anthropoidea have long been major focal points in the study of primate evolution. Field work in Africa and Asia over the past forty years has produced a bewildering array of fossil primates, many having been linked in one way or another with the early origins of anthropoids. Asia recently has become fashionable in some circles as the ultimate geographic source of anthropoids, while Africa remains a viable alternative for others. In this paper we discuss the history of discovery of the Eocene primates of Myanmar and then offer our views on the current status of these Myanmar primates in the ongoing debate over anthropoid origins.
Effects of agglomeration on the properties of spray‐dried encapsulated flavours
Authors: Buffo R. A. , Probst K. , Zehentbauer G. , Luo Z. , Reineccius G. A.
Published: October 2002

A flavour model system was encapsulated by spray‐drying, using traditional carrier materials, and then subjected to agglomeration by fluidized bed processing. Flavour retention was not adversely affected by the secondary processing as long as agglomeration did not promote structure collapse. Agglomerated powders showed higher moisture contents, absolute densities and mean particle sizes than spray‐dried‐only powders. Surface oil decreased in the agglomerated powders as a consequence of the stripping effect in the agglomerator, but this reduction was not necessarily correlated with better shelf‐life. In general, agglomeration did not considerably change the properties of the powders beyond the limitations inherently associated with the carriers employed. Copyright © 2002 John Wiley & Sons, Ltd.
Chemical composition and antioxidant activity of essential oils from Algerian Origanum glandulosum Desf.
Authors: Ruberto Giuseppe , Baratta M. Tiziana , Sari Madani , Kaâbeche Mohamed
Published: October 2002

The essential oils obtained from Origanum glandulosum Desf., collected in four different localities of the Sètif region (north‐eastern Algeria), were analysed by GC–MS and assayed for their antioxidative effectiveness. The antioxidant capacity of the oils was measured by the modified thiobarbituric acid reactive species (TBARS) assay, using egg yolk as oxidizable substrate in presence of the radical inducer 2,2′‐azobis‐(2‐amidinopropane) dihydrochloride (ABAP). The activity was compared with those of α‐tocopherol and 2,6‐di‐tertbutyl‐4‐methyl phenol (BHT, butylated hydroxytoluene). The four oils were also endowed with a high degree of activity at the lowest concentration (100 ppm). This activity is to be ascribed to the high content of phenol components, viz. thymol and carvacrol, which strongly characterize the composition of these oils. Copyright © 2002 John Wiley & Sons, Ltd.
On pressure boundary conditions for thermoconvective problems
Authors: Herrero H. , Mancho A. M.
Published: October 2002

Solving numerically hydrodynamical problems of incompressible fluids raises the question of handling first order derivatives (those of pressure) in a closed container and determining its boundary conditions. A way to avoid the first point is to derive a Poisson equation for pressure, although the problem of taking the right boundary conditions still remains. To remove this problem another formulation of the problem has been used consisting of projecting the master equations into the space of divergence‐free velocity fields, so pressure is eliminated from the equations. This technique raises the order of the differential equations and additional boundary conditions may be required. High‐order derivatives are sometimes troublesome, specially in cylindrical coordinates due to the singularity at the origin, so for these problems a low order formulation is very convenient. We research several pressure boundary conditions for the primitive variables formulation of thermoconvective problems. In particular we study the Marangoni instability of an infinite fluid layer and we show that the numerical results with a Chebyshev collocation method are highly correspondent to the exact ones. These ideas have been applied to linear stability analysis of the Bénard–Marangoni (BM) problem in cylindrical geometry and the results obtained have been very accurate. Copyright © 2002 John Wiley & Sons, Ltd.
Measuring implied volatility: Is an average better? Which average?
Authors: Ederington Louis H. , Guan Wei
Published: October 2002

Options researchers have argued that by averaging together implied standard deviations, or ISDs, calculated

from several options with the same expiry but different strikes, the noise in individual ISDs can be reduced,

yielding a better measure of the market's volatility expectation. Various options researchers have suggested

different weighting schemes for calculating these averages. In the forecasting literature, econometricians have

made the same argument but suggested quite different weighting schemes. Ignoring both literatures, commercial

vendors calculate ISD averages using their own weightings. We compare the averages proposed in both the options

and econometrics literatures and the averages used by major commercial vendors for the S&P 500 futures

options market. Although some averages forecast better than others, we find that the question of the best

weighting scheme is of secondary importance. More important is the fact that the ISDs are upward biased measures

of expected volatility. Fortunately, this bias is stable over time, so past bias patterns can be used to obtain

unbiased volatility forecasts. Once this is done, most ISD averages forecast better than time series and naive

models, and the differences between the averages produced by the various proposed weighting schemes are small.

© 2002 Wiley Publications, Inc. Jrl Fut Mark 22:811–837, 2002
Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer
Authors: Logan Malcolm , Martin James F. , Nagy Andras , Lobe Corrinne , Olson Eric N. , Tabin Clifford J.
Published: October 2002

Summary: We have used a Prx1 limb enhancer to drive expression of Cre Recombinase in transgenic mice. This regulatory element leads to Cre expression throughout the early limb bud mesenchyme and in a subset of craniofacial mesenchyme. Crossing a murine line carrying this transgene to a reporter mouse harboring a floxed Cre‐reporter cassette revealed that recombinase activity is first observed in the earliest limb bud at 9.5 dpc. By early to mid bud stages at 10.5 dpc recombination is essentially complete in all mesenchymal cells in the limb. Expression of the Cre recombinase was never detected in the limb bud ectoderm. The use of Prx1–Cre mice should facilitate analysis of gene function in the developing limb. genesis 33:77–80, 2002. © 2002 Wiley‐Liss, Inc.
Efficient in vitro and in vivo excision of floxed sequences with a high‐capacity adenoviral vector expressing CRE recombinase
Authors: Badorf Michael , Edenhofer Frank , Dries Volker , Kochanek Stefan , Schiedner Gudrun
Published: October 2002

Summary: Conditional gene expression or gene disruption using Cre/loxP‐ or FLP/frt‐based recombination systems are valuable tools for studying gene function in development and disease. Recombinant adenoviral vectors expressing Cre recombinase have been suggested as an alternative for deletion of floxed sequences. To further improve this approach we generated a high‐capacity adenoviral (HC‐Ad) vector expressing Cre (HC‐Adcre). In this vector all viral coding sequences are deleted resulting in decreased toxicity. In the present study HC‐Adcre efficiently mediated recombination between two loxP sites located in the genome of a reporter cell line. When intravenously injected into ROSA26 reporter mice, a floxed sequence was excised in hepatocytes resulting in expression of the β‐gal reporter. Our data indicate that HC‐Ad vectors expressing Cre effectively delete floxed sequences in vivo and have a significant potential as a tool for functional studies in mice. genesis 33:119–124, 2002. © 2002 Wiley‐Liss, Inc.
Sertoli and granulosa cell‐specific Cre recombinase activity in transgenic mice
Authors: Lécureuil Charlotte , Fontaine Isabelle , Crepieux Pascale , Guillou Florian
Published: October 2002

We have established transgenic mice expressing the Cre recombinase under the control of the anti‐Müllerian hormone (AMH) gene promoter. Cre activity and specificity were evaluated by different means. In AMH‐Cre mice, expression of the Cre recombinase mRNA was confined to the testis and ovary. AMH‐Cre mice were crossed with reporter transgenic lines and the offspring exhibited Cre‐mediated recombination only in the testis and the ovary. In male, histochemical analysis indicated that recombination occured in every Sertoli cells. In female, Cre‐mediated recombination was restricted to granulosa cells, but the protein was not evenly active in every cells. From these results, we conclude that potentially, this transgenic line possessing AMH promoter‐driven expression of the Cre recombinase is a powerful tool to delete genes in Sertoli cells only, in order to study Sertoli cell gene function during mammalian spermatogenesis. genesis 33:114–118, 2002. © 2002 Wiley‐Liss, Inc.
Empirical bayes methods and false discovery rates for microarrays
Authors: Efron Bradley , Tibshirani Robert
Published: October 2002

In a classic two‐sample problem, one might use Wilcoxon's statistic to test for a difference between treatment and control subjects. The analogous microarray experiment yields thousands of Wilcoxon statistics, one for each gene on the array, and confronts the statistician with a difficult simultaneous inference situation. We will discuss two inferential approaches to this problem: an empirical Bayes method that requires very little a priori Bayesian modeling, and the frequentist method of “false discovery rates” proposed by Benjamini and Hochberg in 1995. It turns out that the two methods are closely related and can be used together to produce sensible simultaneous inferences. Genet. Epidemiol. 23:70–86, 2002. © 2002 Wiley‐Liss, Inc.
Chlorotoxin, a scorpion‐derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin
Authors: Lyons Susan A. , O'Neal Jeffrey , Sontheimer Harald
Published: October 2002

Highly migratory neuroectodermal cells share a common embryonic origin with cells of the central nervous system (CNS). They include enteric, parasympathetic, sympathoadrenal, and sensory neurons of the peripheral nervous system, Schwann cells, melanocytes, endocrine cells, and cells forming connective tissue of the face and neck. Because of their common embryologic origin, these cells and the tumors that derive from them can share genetic and antigenic phenotypes with gliomas, tumors derived from CNS glia. We recently discovered that chlorotoxin (ClTx), a 4‐kD peptide purified from Leiurus quinquestriatus scorpion, is a highly specific marker for glioma cells in biopsy tissues (Soroceanu et al. Cancer Res 58:4871–4879, 1998) that can target tumors in animal models. We report on the specificity of ClTx as a marker for tumors of neuroectodermal origin that include peripheral neuroectodermal tumors (PNET) and gliomas. Specifically, we histochemically stained frozen and paraffin tissue sections of human biopsy tissues from 262 patients with a synthetically manufactured and biologically active ClTx bearing an N‐terminal biotin. The vast majority (74 of 79) of primary human brain tumors investigated showed abundant binding of ClTx with greater than 90% ClTx‐positive cells in each section. By comparison, 32 biopsies of uninvolved brain used for comparison were largely ClTx‐negative, with only a few isolated reactive astrocytes showing some ClTx binding. However, as with gliomas, the vast majority of PNETs examined showed specific ClTx binding (31 of 34). These include medulloblastomas (4 of 4), neuroblastomas (6 of 7), ganglioneuromas (4 of 4), melanomas (7 of 7), adrenal pheochromocytomas (5 of 6), primitive PNET (1), small cell lung carcinoma (2 of 3), and Ewing's sarcoma (2 of 2). Under identical staining conditions, normal tissues from brain, skin, kidney, and lung were consistently negative for ClTx. These results suggest that chlorotoxin is a reliable and specific histopathological marker for tumors of neuroectodermal origin and that chlorotoxin derivatives with cytolytic activity may have therapeutic potential for these cancers. GLIA 39:162–173, 2002. © 2002 Wiley‐Liss, Inc.
Challenging behaviours in nursing home residents with dementia: a randomized controlled trial of multidisciplinary interventions
Authors: Opie Janet , Doyle Colleen , O'Connor Daniel W.
Published: October 2002

Objectives

To test the premise that individually tailored psychosocial, nursing and medical interventions to nursing home residents with dementia will reduce the frequency and severity of behavioural symptoms.

Methods

A four‐member team comprising a psychiatrist, psychologist and nurses conducted detailed assessments of 99 nursing home residents with advanced dementia who were rated by staff as having frequent, severe behavioural disturbances. Residents were then randomly assigned to an ‘early’ or ‘late’ intervention group and observed for four weeks. Interventions encompassed psychosocial strategies, nursing approaches, psychotropic medications and management of pain. Outcome measures included the frequency and severity of disruptive behaviours and assessments of change by senior nursing home staff.

Results

While improvements in behaviour were noted in both groups from the outset of observations, pointing to a powerful Hawthorne effect, consultancies were associated with a modest but statistically significant decrease in challenging behaviours. Staff assessments of the interventions were highly favourable.

Conclusions

The consultancies were effective and well received by staff. The change‐inducing nature of any new endeavour is an integral part of research in a long‐term setting. Copyright © 2002 John Wiley & Sons, Ltd.
Comparing clock tests for dementia screening: naïve judgments vs formal systems—what is optimal?
Authors: Scanlan James M. , Brush Michael , Quijano Christina , Borson Soo
Published: October 2002

Background

Clock drawing tests (CDTs) vary in format, scoring, and complexity. Herein, we compared the dementia screening performance of seven CDT scoring systems and the judgements of untrained raters.

Methods

80 clock drawings by subjects of known dementia status were selected, 20 from each of four categories (Consortium to Establish a Registry for Alzheimer's disease [CERAD] defined normal, mild, moderate, and severe abnormality). An expert rater scored all clocks using published criteria for seven systems. Additionally, 20 naïve raters judged clocks as either normal or abnormal, without formal instructions. Clocks were then classified by drawers' dementia status for comparison of dementia detection across systems.

Results

Naïve and formal CDT systems showed 90–100% agreement in CERAD normal, moderate and severe categories, but poor agreement (mean = 39%) for mildly impaired clocks. When CDT systems were compared for accurate dementia classification, the Mendez and CERAD systems correctly identified the greatest proportion of subjects (84–85%), and Wolf‐Klein the smallest (58%). The better systems correctly identified> 70% of mildly demented individuals (CDR = 1). In contrast, medical records from patients' personal physicians correctly identified only 24% of the mildly demented. Strikingly, naïve raters' CDT judgements were as effective as five of the seven CDT systems in dementia identification.

Conclusions

While the Mendez system was the most accurate overall, it was not significantly better than CERAD, which had simpler scoring rules. Untrained raters discriminated normal from abnormal clocks with acceptable accuracy for community screening purposes. Results suggest that, if used, most CDT systems would improve personal physicians' dementia recognition in difficult to detect mildly demented subjects. Copyright © 2002 John Wiley & Sons, Ltd.
Mini Mental State Examination in Sinhalese: a sensitive test to screen for dementia in Sri Lanka
Authors: de Silva H. A. , Gunatilake S.B.
Published: October 2002

Background

Although the Sri Lankan population is ageing rapidly, dementia has not been systematically investigated here. The Mini Mental State Examination (MMSE) is a brief global instrument used to assess cognitive abilities in the elderly.

Objective

This study aimed to develop and validate a Sinhalese translation of the MMSE, which could be used as a screening instrument to detect impaired cognition in an epidemiological investigation of dementia in Sri Lanka.

Methods

Due to the high literacy rate in the country, the MMSE was translated and modified slightly without having to make major changes to the original version. 380 randomly selected subjects over 65 years in a semi‐urban area were screened with the translated version of the MMSE. The cut‐off score for cognitive impairment was taken as 17. Of the 380 subjects screened, 33 scored ≤ 17, and were thus considered cases of suspected dementia. All 33 who scored ≤ 17 and 24 randomly selected subjects who scored > 17 on the MMSE, thus considered cognitively normal, underwent a brief clinical examination and neuropsychological assessment with the more comprehensive neuropsychiatric test battery, Cambridge Cognitive Score (CAMCOG), to determine the presence of dementia.

Results

Evaluated against the performance at the CAMCOG, the sensitivity and specificity of the translated MMSE were 93.5% and 84.6% respectively.

Conclusion

Therefore, the Sinhalese translation of the MMSE described here is a sensitive instrument to screen for dementia in Sri Lanka. Copyright © 2002 John Wiley & Sons, Ltd.
The effect of selegiline in the treatment of people with Alzheimer's disease: a meta‐analysis of published trials
Authors: Wilcock G. K. , Birks J. , Whitehead A. , Evans Sir John Grimley
Published: October 2002

Objective

To evaluate the effect of selegiline in the treatment of patients with Alzheimer's disease, in terms of cognitive performance, functional ability, emotional state (including behaviour and mood) and global response.

Data Sources

The Cochrane database of trials, Embase, Medline and Psychlit.

Study Selection

Unconfounded, double‐blind, randomised trials of selegiline compared with placebo reported before 31 December 1998.

Data Extraction

The reviewers selected trials for inclusion. Individual patient data were sought, but when these could not be retrieved summary data were extracted from published papers.

Results

Of 27 identified trials, 14 met the inclusion criteria. Individual patient data were retrieved from eight trials on 821 patients. Summary data were extracted from five trials on 240 patients. No data were available from one trial on 12 patients, which was therefore excluded from the meta‐analysis. Fixed and random effects meta‐analyses were performed on standardised mean differences. For cognition there was a statistically significant difference between selegiline and placebo at 4–6 weeks and 8–17 weeks after randomisation (at 8–17 weeks: smd=0.45 [95% confidence interval 0.03 to 0.88]), but this disappeared at later assessments. The size of the treatment difference was considered unlikely to be of clinical importance. Although there was a statistically significant difference at 4–6 weeks for activities of daily living, this disappeared at later assessments (at 8–17 weeks: smd=0.33 [−0.33, 0.69]). There were no statistically significant differences or clinically relevant differences between selegiline and placebo in terms of emotional state or global response.

Conclusion

Although there was some evidence of improvement with selegiline in the short term in cognition and activities of daily living, the magnitude of the effect did not reach clinical importance. There was no evidence of long term effects. Copyright © 2002 John Wiley & Sons, Ltd.
Positive aspects of caregiving: rounding out the caregiver experience
Authors: Cohen Carole A. , Colantonio Angela , Vernich Lee
Published: October 2002

Objectives

To identify positive aspects of caregiving and examine how they are associated with caregiver outcomes.

Method

This study used a national sample of caregivers derived from the Canadian Study of Health and Aging (part 2). Two hundred and eighty‐nine caregivers caring for seniors living in the community were questioned about their experience of caregiving. Caregivers were asked whether they could identify any positive aspects related to their role, the type of positive aspects and to rate their feelings about caring. Using a conceptual model developed by Noonan and Tennstedt (1997), a staged stepwise multiple regression approach was used factoring the background/contextual variables, stressor variables (3 MS score, ADL limitations), mediator variables (positive aspects of caregiving, number of services used) and outcome variables (depression, burden and self‐assessed health measures) into the model.

Results

Two hundred and eleven caregivers (73%) could identify at least one specific positive aspect of caregiving. An additional 20 (6.9%) could identify more than one positive aspect. Positive feelings about caring were associated with lower CES‐D scores ( p < 0.001), lower burden scores ( p < 0.001) and better self assessed health ( p < 0.001).

Conclusion

Clinicians should inquire about the positive aspects of caregiving if they are to fully comprehend the caregiver experience and identify risk factors for negative caregiver outcomes. Copyright © 2002 John Wiley & Sons, Ltd.
Incidence, prevalence, and outcomes of depression in residents of a long‐term care facility with dementia
Authors: Payne Jennifer L. , Sheppard Jeannie‐Marie E. , Steinberg Martin , Warren Andrew , Baker Alva , Steele Cynthia , Brandt Jason , Lyketsos Constantine G.
Published: October 2002

Background

The course of depression in residents of long‐term care with dementia is not well studied.

Objectives

To estimate the incidence, prevalence, and outcomes of depression in long‐term care residents with dementia.

Method

201 residents of Copper Ridge, a long‐term care facility for the memory impaired, were followed every six months during the first year after their admission.

Results

On admission 19.9% of the residents had depression, the majority (75%) occurring in persons with a prior history of depression. At six months, only 15% of the original 40 depressed patients were still depressed, while at twelve months only 7.5% were depressed. The incidence of depression at six and twelve months was 1.8% and 6.4% respectively. Most persons with new depression at six months were no longer depressed at one year. The annual attack rate (cumulative likelihood of depression over one year) for the total population was 26.4%. The rates for the subgroup of Alzheimer's were similar to the rates of the total population, except for an annual attack rate of 17.5%, reflecting a lower rate of depression on admission. The decline in depression over the year after admission is noteworthy and likely reflects appropriate diagnosis and treatment of depression.

Conclusions

These results indicate that, over the course of one year, depression afflicts a considerable proportion of long‐term care residents with dementia. Admission to a long‐term care facility may actually result in a reduction of depression within the year after admission in part due to rapid recognition, appropriate diagnosis and treatment. Copyright © 2002 John Wiley & Sons, Ltd.
Olanzapine associated weight gain, Hyperglycemia and Neuroleptic Malignant Syndrome: case report
Authors: Malyuk Rhonda , Gibson Bruce , Procyshyn Ric M. , Kang Nirmal
Published: October 2002

We describe here a case of olanzapine associated weight gain, hyperglycemia and neuroleptic malignant syndrome in a 64 year‐old woman with a significant medical history. Eighteen weeks after initiating olanzapine, Mrs X lost glycemic control, exhibited signs and symptoms consistent with neuroleptic malignant syndrome and gained 8.9 kg. We suggest that utilization of olanzapine in the less medically stable geriatric patient be implemented with vigilant monitoring for such complications mentioned above. Copyright © 2002 John Wiley & Sons, Ltd.
The prevalence and phenomenology of auditory hallucinations among elderly subjects attending an audiology clinic
Authors: Cole Martin G. , Dowson Lorna , Dendukuri Nandini , Belzile Eric
Published: October 2002

Background

Studies of auditory hallucinations are scant.

Method

To determine the prevalence and phenomenology of auditory hallucinations among elderly subjects with hearing impairment.

Objective

We surveyed 125 men and women aged 65 years and over referred to the Audiology department of a university‐affiliated primary acute‐care hospital.

Results

The prevalence of auditory hallucinations was 32.8% (95% confidence interval (CI) 24.7–41.8). These hallucinations represented a spectrum of phenomenology from elementary personal impressions to complex percepts. The types of auditory hallucinations included humming or buzzing (35.9%), shushing (12.8%), beating or tapping (10.6%), ringing (7.7%), other individual sounds (15.4%), multiple sounds (12.6%), voices (2.5%) or music (2.5%). Subjects with any type of hallucination were younger and had poorer discrimination scores in the left ear and impaired binaural discrimination with lip‐reading. Subjects with hallucinations that had more qualities of a true percept heard different types of sounds and had lower reflex thresholds and better air conduction in the right ear.

Conclusion

Auditory hallucinations are frequent in elderly subjects with hearing impairment and seem to be associated with younger age and asymmetrical hearing impairment. Copyright © 2002 John Wiley & Sons, Ltd.