Publications by authors named "Pierre Gérard"

15 Publications

  • Page 1 of 1

The combination of an innovative dry powder for inhalation and a standard cisplatin-based chemotherapy in view of therapeutic intensification against lung tumours.

Eur J Pharm Biopharm 2021 Jul 3;164:93-104. Epub 2021 May 3.

Unit of Pharmaceutics and Biopharmaceutics, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Brussels, Belgium.

Cisplatin is one of the most commonly used chemotherapy in lung cancer despite its high nephrotoxicity leading to an administration only every 3-4 weeks. This study is the first report of a preclinical investigation of therapeutic intensification combining a cisplatin dry powder for inhalation (CIS-DPI) with an intravenous (iv) cisplatin-based treatment. CIS-DPI with 50% cisplatin content (CIS-DPI-50) was developed using lipid excipients through scalable processes (high-speed and high-pressure homogenization and spray-drying). CIS-DPI-50 showed good aerodynamic performance (fine particle fraction of ~ 55% and a mass median aerodynamic particle size of ~ 2 µm) and a seven-fold increase and decrease in C in the lungs and in plasma, respectively, in comparison with an iv cisplatin solution (CIS-iv) in healthy mice. Finally, the addition of CIS-DPI-50 to the standard cisplatin/paclitaxel iv doublet increased the response rate (67% vs 50%), decreased the tumour growth and prolonged the median survival (31 vs 21 days), compared to the iv doublet in the M109 lung carcinoma model tending to demonstrate a therapeutic intensification of cisplatin.
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http://dx.doi.org/10.1016/j.ejpb.2021.04.018DOI Listing
July 2021

When a pH-triggered nanopatterned shape transition drives the wettability of a hierarchically self-organized film: A bio-inspired effect of "sea Anemone".

J Colloid Interface Sci 2021 Jan 29;581(Pt A):96-101. Epub 2020 Jul 29.

Universite de Pau et Pays Adour, E2S UPPA, CNRS, IPREM UMR 5254, 2 avenue du Président Angot, Pau F-64053, France; Bio-inspired Materials Group: Functionalities & Self-assembly, Universite de Pau et Pays Adour, 2 avenue du Président Angot, Pau F-64053, France. Electronic address:

Hypothesis: Hierarchically structured surfaces including sensitive materials presents the advantage to exalt wettability variation due to the combination of micro structure effect directed by Cassie Baxter and/or Wenzel behaviour which is tuned by the surface energy variation of sensitive polymer films.

Experiments: Herein is reported the synthesis and the hierarchical structuration of a pH sensitive diblock copolymer P(S-stat-MMA)-b-P4VP with a pH-sensitive Poly 4-vinylpyridine P4VP block. Applying the Breath Figure method casting (minute time scale process), this diblock copolymer allows to obtain a micro porous honeycomb film while a wall nano-structuration due to self-assembly of diblock copolymer is observed.

Findings: The pH-triggered wettability is studied and correlated with the morphology evolution of P4VP nano-domains investigated by AFM in a liquid cell. Indeed, a nano-dots to nano-rings/donuts transition is highlighted when decreasing the pH below the pKa of the P4VP. This nano "sea Anemone" shape transition induces the macroscopic changes of the wettability of a hierarchically self-organized honeycomb film, explained by the protonation of P4VP chains inducing electrostatic repulsion and then hydrophilic surface.
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http://dx.doi.org/10.1016/j.jcis.2020.07.130DOI Listing
January 2021

X-chromosome meiotic drive in Drosophila simulans: a QTL approach reveals the complex polygenic determinism of Paris drive suppression.

Heredity (Edinb) 2019 06 5;122(6):906-915. Epub 2018 Dec 5.

Evolution Génome Comportement et Ecologie, CNRS, IRD, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, 91190, Paris, France.

Meiotic drivers are selfish genetic elements that promote their own transmission into the gametes, which results in intragenomic conflicts. In the Paris sex-ratio system of Drosophila simulans, drivers located on the X chromosome prevent the segregation of the heterochromatic Y chromosome during meiosis II, and hence the production of Y-bearing sperm. The resulting sex-ratio bias strongly impacts population dynamics and evolution. Natural selection, which tends to restore an equal sex ratio, favors the emergence of resistant Y chromosomes and autosomal suppressors. This is the case in the Paris sex-ratio system where the drivers became cryptic in most of the natural populations of D. simulans. Here, we used a quantitative trait locus (QTL) mapping approach based on the analysis of 152 highly recombinant inbred lines (RILs) to investigate the genetic determinism of autosomal suppression. The RILs were derived from an advanced intercross between two parental lines, one showing complete autosomal suppression while the other one was sensitive to drive. The confrontation of RIL autosomes with a reference X chromosome allowed us to identify two QTLs on chromosome 2 and three on chromosome 3, with strong epistatic interactions. Our findings highlight the multiplicity of actors involved in this intragenomic battle over the sex ratio.
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http://dx.doi.org/10.1038/s41437-018-0163-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781156PMC
June 2019

Polyploidy and interspecific hybridization: partners for adaptation, speciation and evolution in plants.

Ann Bot 2017 08;120(2):183-194

Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.

Background: Polyploidy or whole-genome duplication is now recognized as being present in almost all lineages of higher plants, with multiple rounds of polyploidy occurring in most extant species. The ancient evolutionary events have been identified through genome sequence analysis, while recent hybridization events are found in about half of the world's crops and wild species. Building from this new paradigm for understanding plant evolution, the papers in this Special Issue address questions about polyploidy in ecology, adaptation, reproduction and speciation of wild and cultivated plants from diverse ecosystems. Other papers, including this review, consider genomic aspects of polyploidy.

Approaches: Discovery of the evolutionary consequences of new, evolutionarily recent and ancient polyploidy requires a range of approaches. Large-scale studies of both single species and whole ecosystems, with hundreds to tens of thousands of individuals, sometimes involving 'garden' or transplant experiments, are important for studying adaptation. Molecular studies of genomes are needed to measure diversity in genotypes, showing ancestors, the nature and number of polyploidy and backcross events that have occurred, and allowing analysis of gene expression and transposable element activation. Speciation events and the impact of reticulate evolution require comprehensive phylogenetic analyses and can be assisted by resynthesis of hybrids. In this Special Issue, we include studies ranging in scope from experimental and genomic, through ecological to more theoretical.

Conclusions: The success of polyploidy, displacing the diploid ancestors of almost all plants, is well illustrated by the huge angiosperm diversity that is assumed to originate from recurrent polyploidization events. Strikingly, polyploidization often occurred prior to or simultaneously with major evolutionary transitions and adaptive radiation of species, supporting the concept that polyploidy plays a predominant role in bursts of adaptive speciation. Polyploidy results in immediate genetic redundancy and represents, with the emergence of new gene functions, an important source of novelty. Along with recombination, gene mutation, transposon activity and chromosomal rearrangement, polyploidy and whole-genome duplication act as drivers of evolution and divergence in plant behaviour and gene function, enabling diversification, speciation and hence plant evolution.
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http://dx.doi.org/10.1093/aob/mcx079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737848PMC
August 2017

Rapid evolution of a Y-chromosome heterochromatin protein underlies sex chromosome meiotic drive.

Proc Natl Acad Sci U S A 2016 Apr 15;113(15):4110-5. Epub 2016 Mar 15.

Laboratoire Évolution, Génomes, Comportement, Écologie, CNRS, IRD, Université Paris-Sud and Université Paris-Saclay, 91198 Gif-sur-Yvette, France;

Sex chromosome meiotic drive, the non-Mendelian transmission of sex chromosomes, is the expression of an intragenomic conflict that can have extreme evolutionary consequences. However, the molecular bases of such conflicts remain poorly understood. Here, we show that a young and rapidly evolving X-linked heterochromatin protein 1 (HP1) gene, HP1D2, plays a key role in the classical Paris sex-ratio (SR) meiotic drive occurring in Drosophila simulans Driver HP1D2 alleles prevent the segregation of the Y chromatids during meiosis II, causing female-biased sex ratio in progeny. HP1D2 accumulates on the heterochromatic Y chromosome in male germ cells, strongly suggesting that it controls the segregation of sister chromatids through heterochromatin modification. We show that Paris SR drive is a consequence of dysfunctional HP1D2 alleles that fail to prepare the Y chromosome for meiosis, thus providing evidence that the rapid evolution of genes controlling the heterochromatin structure can be a significant source of intragenomic conflicts.
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http://dx.doi.org/10.1073/pnas.1519332113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839453PMC
April 2016

Are basal and glucagon-stimulated C-peptide values predictors of response to GLP-1 receptor agonists in type 2 diabetic patients?

Minerva Endocrinol 2016 Mar;41(1):138-40

Endocrinology and Metabolic Diseases Unit, Groupe Hospitalier Sud Reunion, Saint-Pierre, Reunion Island, France -

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March 2016

Sex chromosome drive.

Cold Spring Harb Perspect Biol 2014 Dec 18;7(2):a017616. Epub 2014 Dec 18.

Laboratoire Évolution Génomes et Spéciation, CNRS UPR9034, Gif-sur-Yvette, France and Université Paris-Sud, Orsay, France.

Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species.
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http://dx.doi.org/10.1101/cshperspect.a017616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315933PMC
December 2014

Ultra-low power high temperature and radiation hard complementary metal-oxide-semiconductor (CMOS) silicon-on-insulator (SOI) voltage reference.

Sensors (Basel) 2013 Dec 13;13(12):17265-80. Epub 2013 Dec 13.

ICTEAM Institute-Electrical Engineering, Université catholique de Louvain, Maxwell Building, Place du Levant 3, B-1348 Louvain-la-Neuve, Belgium.

This paper presents an ultra-low power CMOS voltage reference circuit which is robust under biomedical extreme conditions, such as high temperature and high total ionized dose (TID) radiation. To achieve such performances, the voltage reference is designed in a suitable 130 nm Silicon-on-Insulator (SOI) industrial technology and is optimized to work in the subthreshold regime of the transistors. The design simulations have been performed over the temperature range of -40-200 °C and for different process corners. Robustness to radiation was simulated using custom model parameters including TID effects, such as mobilities and threshold voltages degradation. The proposed circuit has been tested up to high total radiation dose, i.e., 1 Mrad (Si) performed at three different temperatures (room temperature, 100 °C and 200 °C). The maximum drift of the reference voltage V(REF) depends on the considered temperature and on radiation dose; however, it remains lower than 10% of the mean value of 1.5 V. The typical power dissipation at 2.5 V supply voltage is about 20 μW at room temperature and only 75 μW at a high temperature of 200 °C. To understand the effects caused by the combination of high total ionizing dose and temperature on such voltage reference, the threshold voltages of the used SOI MOSFETs were extracted under different conditions. The evolution of V(REF) and power consumption with temperature and radiation dose can then be explained in terms of the different balance between fixed oxide charge and interface states build-up. The total occupied area including pad-ring is less than 0.09 mm2.
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http://dx.doi.org/10.3390/s131217265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892812PMC
December 2013

Local dynamics of a fast-evolving sex-ratio system in Drosophila simulans.

Mol Ecol 2013 Nov 5;22(21):5352-67. Epub 2013 Oct 5.

Laboratoire Evolution Génomes Spéciation, CNRS, 91198, Gif-sur-Yvette Cedex, France; Université Paris-Sud, 91405, Orsay Cedex, France.

By distorting Mendelian transmission to their own advantage, X-linked meiotic drive elements can rapidly spread in natural populations, generating a sex-ratio bias. One expected consequence is the triggering of a co-evolutionary arms race between the sex chromosome that carries the distorter and suppressors counteracting its effect. Such an arms race has been theoretically and experimentally established and can have many evolutionary consequences. However, its dynamics in contemporary populations is still poorly documented. Here, we investigate the fate of the young X-linked Paris driver in Drosophila simulans from sub-Saharan Africa to the Middle East. We provide the first example of the early dynamics of distorters and suppressors: we find consistent evidence that the driving chromosomes have been rising in the Middle East during the last decade. In addition, identical haplotypes are at high frequencies around the two co-evolving drive loci in remote populations, implying that the driving X chromosomes share a recent common ancestor and suggesting that East Africa could be the cradle of the Paris driver. The segmental duplication associated with drive presents an unusual structure in West Africa, which could reflect a secondary state of the driver. Together with our previous demonstration of driver decline in the Indian Ocean where suppression is complete, these data provide a unique picture of the complex dynamics of a co-evolutionary arms race currently taking place in natural populations of D. simulans.
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http://dx.doi.org/10.1111/mec.12492DOI Listing
November 2013

Abundant genetic variability in Drosophila simulans for hybrid female lethality in interspecific crosses to Drosophila melanogaster.

Genet Res (Camb) 2012 Feb;94(1):1-7

Department of Biology, University of Rochester, NY 14627, USA.

Intrinsic postzygotic reproductive isolation is thought to result from the substitution of multiple harmless or beneficial genetic differences between species that are incidentally deleterious when combined in species hybrids, causing hybrid sterility or inviability. Genetic variability for hybrid sterility or inviability phenotypes is, however, rarely assessed in natural populations. Here, we assess variation for Drosophila simulans-encoded maternal factor(s) that cause lethality in D. simulans-Drosophila melanogaster F(1) hybrid females. First, we survey genetic variability in the strength of D. simulans-mediated maternal effect hybrid lethality among 37 geographic and laboratory isolates. We find abundant variability in the strength of maternal effect hybrid lethality, ranging from complete lethality to none. Second, we assess maternal effect hybrid lethality for a subset of wild isolates made heterozygous with two so-called hybrid rescue strains. The results suggest that the D. simulans maternal effect hybrid lethality involves a diversity of alleles and/or multiple loci.
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http://dx.doi.org/10.1017/S0016672312000031DOI Listing
February 2012

Large-scale selective sweep among Segregation Distorter chromosomes in African populations of Drosophila melanogaster.

PLoS Genet 2009 May 1;5(5):e1000463. Epub 2009 May 1.

Department of Biology, University of Rochester, Rochester, NY, USA.

Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD(+) males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1-5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (approximately 2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome.
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http://dx.doi.org/10.1371/journal.pgen.1000463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668186PMC
May 2009

Comparison of Genetic and Virulence Diversity of Melampsora larici-populina Populations on Wild and Cultivated Poplar and Influence of the Alternate Host.

Phytopathology 2006 Sep;96(9):1027-36

ABSTRACT The aims of this study were, first, to compare the genetic and virulence diversity between populations of the rust fungus Melampsora larici-populina on wild and cultivated poplar stands and, second, to investigate the influence of the presence of the alternate host of the pathogen, larch, on which its sexual reproduction occurs, on these diversities. Nine French M. larici-populina populations collected from poplar trees in autumn and four populations collected from larch trees during the following spring were analyzed using both virulence factors and neutral markers. In all, 30 pathotypes were identified within the 13 populations studied. The pathotypic structure clearly distinguished the cultivated stands with high richness and complexity from the wild stands with low richness and complexity. High linkage disequilibria between virulences indicated preferential virulence associations, probably due to selection by the host. In all, 19 random amplified polymorphic DNA (RAPD) markers were used, which revealed a very high genetic diversity in the 743 isolates analyzed. The nine populations from poplar appeared moderately differentiated, indicating long-distance gene flow, and no isolation by distance was found. Linkage disequilibria between RAPD markers generally were low, indicating frequent recombination, but they were not lower in populations located near larch, probably due to long-distance dispersal.
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http://dx.doi.org/10.1094/PHYTO-96-1027DOI Listing
September 2006

Assortative mating and differential male mating success in an ash hybrid zone population.

BMC Evol Biol 2006 Nov 15;6:96. Epub 2006 Nov 15.

Laboratoire Ecologie, Systématique, Evolution, UMR ENGREF-CNRS 8079, Bât, 360, Université Paris-Sud, 91405 Orsay Cedex, France.

Background: The structure and evolution of hybrid zones depend mainly on the relative importance of dispersal and local adaptation, and on the strength of assortative mating. Here, we study the influence of dispersal, temporal isolation, variability in phenotypic traits and parasite attacks on the male mating success of two parental species and hybrids by real-time pollen flow analysis. We focus on a hybrid zone population between the two closely related ash species Fraxinus excelsior L. (common ash) and F. angustifolia Vahl (narrow-leaved ash), which is composed of individuals of the two species and several hybrid types. This population is structured by flowering time: the F. excelsior individuals flower later than the F. angustifolia individuals, and the hybrid types flower in-between. Hybrids are scattered throughout the population, suggesting favorable conditions for their local adaptation. We estimate jointly the best-fitting dispersal kernel, the differences in male fecundity due to variation in phenotypic traits and level of parasite attack, and the strength of assortative mating due to differences in flowering phenology. In addition, we assess the effect of accounting for genotyping error on these estimations.

Results: We detected a very high pollen immigration rate and a fat-tailed dispersal kernel, counter-balanced by slight phenological assortative mating and short-distance pollen dispersal. Early intermediate flowering hybrids, which had the highest male mating success, showed optimal sex allocation and increased selfing rates. We detected asymmetry of gene flow, with early flowering trees participating more as pollen donors than late flowering trees.

Conclusion: This study provides striking evidence that long-distance gene flow alone is not sufficient to counter-act the effects of assortative mating and selfing. Phenological assortative mating and short-distance dispersal can create temporal and spatial structuring that appears to maintain this hybrid population. The asymmetry of gene flow, with higher fertility and increased selfing, can potentially confer a selective advantage to early flowering hybrids in the zone. In the event of climate change, hybridization may provide a means for F. angustifolia to further extend its range at the expense of F. excelsior.
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http://dx.doi.org/10.1186/1471-2148-6-96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1660552PMC
November 2006

Temporal cline in a hybrid zone population between Fraxinus excelsior L. and Fraxinus angustifolia Vahl.

Mol Ecol 2006 Oct;15(12):3655-67

Ecologie, Systématique, Evolution, UMR CNRS-UPXI-ENGREF 8079, Bât. 360, Université Paris-Sud, 91405 Orsay cedex, France.

The two closely related ash species Fraxinus excelsior L. (common ash) and Fraxinus angustifolia Vahl (narrow-leaved ash) have a broad contact zone in France where they hybridize. However, little is known about the local structure of hybrid zone populations and the isolation mechanisms. We assessed the potential effect of floral phenology on the structure of a riparian ash hybrid zone population in central France. The distribution of flowering times was unimodal and lay between the flowering periods of the two species. Using microsatellite markers, we detected isolation by time, which has possibly originated from assortative mating. Multivariate analyses indicated that morphological variation is not distributed at random with respect to flowering times. Spatial autocorrelation analyses showed that temporal and spatial patterns were tightly linked. Interestingly, despite the fact that the population shows isolation by time, neighbourhood size and historical dispersal variance (sigma = 63 m) are similar to those detected in pure stands of F. excelsior where individuals flower rather synchronously and hermaphrodites are not the most frequent sexual type. Trees flowering at intermediate dates, which comprised the majority of the population, produced on average more flowers and fruits. We detected no significant differences in floral parasite infections relative to reproductive timing, although there was a tendency for late flowering trees to suffer from more gall attack. We discuss the impact of temporal variation in fitness traits and their possible role in the maintenance of the hybrid zone.
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http://dx.doi.org/10.1111/j.1365-294X.2006.03032.xDOI Listing
October 2006

Primary squamous-cell carcinoma of the rectum: report of six cases and review of the literature.

Dis Colon Rectum 2002 Nov;45(11):1535-40

Département de Chirurgie Viscérale, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite cedex, France.

Purpose: The majority of colorectal carcinomas diagnosed are adenocarcinomas. Squamous-cell carcinoma is a rare pathologic curiosity. Since 1943, only 18 cases have been described in the medical literature. The aim of this study was to report retrospectively six new cases and to review the medical literature.

Patients: Of the 6 cases, 4 were females, and age ranged from 43 to 93 years. Tumors were located 7 to 12 (mean, 8.5) cm from the anal verge. Five patients underwent surgical resection. Intraoperative radiotherapy was performed in one case. One patient was treated only by external beam radiotherapy. In two cases neoadjuvant combination of external beam radiotherapy and chemotherapy and in one case neoadjuvant contact x-ray treatment were performed. This treatment was followed by external beam radiotherapy in two cases and by chemotherapy in two cases, in patients with lymph node involvement.

Results: The clinical tumor response to radiotherapy was almost complete for the patient who did not undergo surgery. One tumor was sterilized by preoperative radiation. Three patients were alive without recurrence at 6 months, 2 years, and 16 years.

Conclusion: The etiopathogenicity of squamous-cell carcinoma of the rectum is discussed. The prognosis of these tumors seems to be worse than that for adenocarcinoma because of a delayed diagnosis. Surgical resection seems to be the most important treatment. Chemotherapy and especially radiotherapy may have some indications.
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http://dx.doi.org/10.1007/s10350-004-6462-zDOI Listing
November 2002