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  • 1
    Publication Date: 2014-07-22
    Description: A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486207/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whelan, Robert -- Watts, Richard -- Orr, Catherine A -- Althoff, Robert R -- Artiges, Eric -- Banaschewski, Tobias -- Barker, Gareth J -- Bokde, Arun L W -- Buchel, Christian -- Carvalho, Fabiana M -- Conrod, Patricia J -- Flor, Herta -- Fauth-Buhler, Mira -- Frouin, Vincent -- Gallinat, Juergen -- Gan, Gabriela -- Gowland, Penny -- Heinz, Andreas -- Ittermann, Bernd -- Lawrence, Claire -- Mann, Karl -- Martinot, Jean-Luc -- Nees, Frauke -- Ortiz, Nick -- Paillere-Martinot, Marie-Laure -- Paus, Tomas -- Pausova, Zdenka -- Rietschel, Marcella -- Robbins, Trevor W -- Smolka, Michael N -- Strohle, Andreas -- Schumann, Gunter -- Garavan, Hugh -- IMAGEN Consortium -- MH082116/MH/NIMH NIH HHS/ -- P20 GM103644/GM/NIGMS NIH HHS/ -- P20GM103644/GM/NIGMS NIH HHS/ -- P50 DA036114/DA/NIDA NIH HHS/ -- P50DA036114/DA/NIDA NIH HHS/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Aug 14;512(7513):185-9. doi: 10.1038/nature13402. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University College Dublin, Dublin 4, Ireland. ; Department of Radiology, University of Vermont, Burlington, Vermont 05401, USA. ; Vermont Center for Children, Youth, and Families, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Department of Pediatrics, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Institut National de la Sante et de la Recherche Medicale, INSERM CEA Unit 1000 "Imaging &Psychiatry", University Paris Sud, 91400 Orsay, France [2] Department of Psychiatry, Orsay Hospital, 4 place du General Leclerc, 91400 Orsay, France. ; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. ; Institute of Psychiatry, King's College London, London SE5 8AF, UK. ; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland. ; 1] Department of Systems Neuroscience, Universitatsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany [2] Department of Psychology, Stanford University, Stanford, California 94305, USA. ; 1] Institute of Psychiatry, King's College London, London SE5 8AF, UK [2] Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal H3T 1C5, Canada. ; 1] Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany [2] Department of Addictive Behaviour and Addiction Medicine, Heidelberg University, 68159 Mannheim, Germany. ; 14 CEA, DSV, I2BM, Neurospin bat 145, 91191 Gif-Sur-Yvette, France. ; 1] Department of Systems Neuroscience, Universitatsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany [2] Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany. ; Department of Psychiatry and Neuroimaging Center, Technische Universitat Dresden, 01062 Dresden, Germany. ; School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, UK. ; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany. ; Physikalisch-Technische Bundesanstalt (PTB), 10587 Berlin, Germany. ; School of Psychology, University of Nottingham, Nottingham NG7 2RD, UK. ; 1] Institut National de la Sante et de la Recherche Medicale, INSERM CEA Unit 1000 "Imaging &Psychiatry", University Paris Sud, 91400 Orsay, France [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75006 Paris, France. ; 1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Neuroscience Graduate Program, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75006 Paris, France. ; 1] Rotman Research Institute, University of Toronto, Toronto, Ontario M5R 0A3, Canada [2] Montreal Neurological Institute, McGill University, H3A 2B4, Canada. ; The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada. ; Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge CB2 1TN, UK. ; 1] Institute of Psychiatry, King's College London, London SE5 8AF, UK [2] MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, London WC2R 2LS, UK. ; 1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University of Vermont, Burlington, Vermont 05401, USA [3] Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043041" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Alcohol Drinking/*psychology ; Alcoholism/genetics/prevention & control/*psychology ; Artificial Intelligence ; Brain/physiology ; Cognition/physiology ; Environment ; Humans ; Life Change Events ; Longitudinal Studies ; *Models, Theoretical ; Personality/physiology ; Polymorphism, Single Nucleotide ; Psychology ; Reproducibility of Results ; Risk Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-06-13
    Description: During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richiardi, Jonas -- Altmann, Andre -- Milazzo, Anna-Clare -- Chang, Catie -- Chakravarty, M Mallar -- Banaschewski, Tobias -- Barker, Gareth J -- Bokde, Arun L W -- Bromberg, Uli -- Buchel, Christian -- Conrod, Patricia -- Fauth-Buhler, Mira -- Flor, Herta -- Frouin, Vincent -- Gallinat, Jurgen -- Garavan, Hugh -- Gowland, Penny -- Heinz, Andreas -- Lemaitre, Herve -- Mann, Karl F -- Martinot, Jean-Luc -- Nees, Frauke -- Paus, Tomas -- Pausova, Zdenka -- Rietschel, Marcella -- Robbins, Trevor W -- Smolka, Michael N -- Spanagel, Rainer -- Strohle, Andreas -- Schumann, Gunter -- Hawrylycz, Mike -- Poline, Jean-Baptiste -- Greicius, Michael D -- IMAGEN consortium -- 93558/Medical Research Council/United Kingdom -- R01 MH085772-01A1/MH/NIMH NIH HHS/ -- R01NS073498/NS/NINDS NIH HHS/ -- U54 EB020403/EB/NIBIB NIH HHS/ -- Department of Health/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1241-4. doi: 10.1126/science.1255905. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. Laboratory of Neurology and Imaging of Cognition, Department of Neuroscience, University of Geneva, Geneva, Switzerland. jonas.richiardi@unige.ch greicius@stanford.edu. ; Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. ; The War Related Illness and Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA, USA. Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. ; Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. ; Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada. Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Canada. ; Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. ; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. ; Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Department of Psychiatry, Universite de Montreal, Centre Hospitalier Universitaire (CHU) Ste Justine Hospital, Montreal, Canada. ; Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Neurospin, Commissariat a l'Energie Atomique et aux Energies Alternatives, Paris, France. ; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany. ; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA. ; School of Physics and Astronomy, University of Nottingham, Nottingham, UK. ; Institut National de la Sante et de la Recherche Medicale, INSERM Unit 1000 "Neuroimaging and Psychiatry," University Paris Sud, Orsay, France. INSERM Unit 1000 at Maison de Solenn, Assistance Publique Hopitaux de Paris (APHP), Cochin Hospital, University Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Rotman Research Institute, University of Toronto, Toronto, Canada. School of Psychology, University of Nottingham, Nottingham, UK. ; The Hospital for Sick Children, University of Toronto, Toronto, Canada. ; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK. ; Department of Psychiatry and Psychotherapy, and Neuroimaging Center, Technische Universitat Dresden, Dresden, Germany. ; Department of Psychopharmacology, Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, Mannheim, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK. ; Allen Institute for Brain Science, Seattle, WA, USA. ; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA. ; Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. jonas.richiardi@unige.ch greicius@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068849" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Animals ; Brain/metabolism/*physiology ; Female ; Gene Expression ; Humans ; Ion Channels/*genetics ; Magnetic Resonance Imaging ; Male ; Mice ; Nerve Net/metabolism/*physiology ; Neural Pathways/metabolism/physiology ; Polymorphism, Genetic ; Rest/*physiology ; Synapses/metabolism/physiology ; *Transcriptome ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We present measurements of global event shape distributions in the hadronic decays of theZ 0. The data sample, corresponding to an integrated luminosity of about 1.3 pb−1, was collected with the OPAL detector at LEP. Most of the experimental distributions we present are unfolded for the finite acceptance and resolution of the OPAL detector. Through comparison with our unfolded data, we tune the parameter values of several Monte Carlo computer programs which simulate perturbative QCD and the hadronization of partons. Jetset version 7.2, Herwig version 3.4 and Ariadne version 3.1 all provide good descriptions of the experimental distributions. They in addition describe lower energy data with the parameter values adjusted at theZ 0 energy. A complete second order matrix element Monte Carlo program with a modified perturbation scale is also compared to our 91 GeV data and its parameter values are adjusted. We obtained an unfolded value for the mean charged multiplicity of 21.28±0.04±0.84, where the first error is statistical and the second is systematic.
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  • 4
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Three-jet variables constructed from multi-hadronic events produced byZ 0 decays are compared to theoretical calculations assuming a vector gluon or a hypothetical scalar gluon. The data yield conclusive direct evidence for the former case. The distributions of the reduced energy of the second-most energetic jet and of the cosine of the Ellis-Karliner angle are chosen to demonstrate this effect.
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  • 5
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A study ofB meson decays intoDl X final states is presented. In these events, neutral and chargedD mesons originate predominantly fromB + andB 0 decays, respectively. The dilution of this correlation due toD ** production has been taken into account. From 263 700 hadronicZ 0 decays collected in 1991 with the DELPHI detector at the LEP collider, 92D 0→K -π+, 35D +→K -π+π+ and 61D *0→D 0π+ followed byD 0→K -π+ orD 0→K -π+π+π-, are found with an associated lepton of the same charge as the kaon. From theD 0 l - andD *+ l -, the probabilityf d that ab quark hadronizes into aB − (or $$\bar B^0 $$ ) meson is found to be 0.44 ±0.08±0.09, corresponding to a total (B s+Λ b ) hadronization fraction of 0.12 −0.12 +0.24 . By reconstructing the energy of eachB meson, theb quark fragmentation is directly measured for the first time. The mean value of theB meson energy fraction is: $$\left\langle {X_E (B)} \right\rangle = 0.695 \pm 0.015(stat.) \pm 0.029(syst.)$$ ReconstructingD-lepton vertices, the followingB lifetimes are measured: $$\begin{gathered} \tau (B) = 1.27_{ - 0.18}^{ + 0.22} (stat.) \pm 0.15(syst.)ps, \hfill \\ where\bar B \to D^0 \ell ^ - X, \hfill \\ \tau (B) = 1.18_{ - 0.27}^{ + 0.39} (stat.) \pm 0.15(syst.)ps, \hfill \\ where\bar B \to D^ + \ell ^ - X, \hfill \\ \tau (B) = 1.19_{ - 0.19}^{ + 0.25} (stat.) \pm 0.15(syst.)ps \hfill \\ where\bar B \to D^{* + } \ell ^ - X, \hfill \\ \end{gathered} $$ and an average τ(B)=1.23 −0.13 +0.14 (stat.)±0.15(syst.) ps is found. Allowing for decays into $$D**\ell ^ - \bar v$$ , theB + andB 0 lifetimes are: $$\begin{gathered} \tau (B^ + ) = 1.30_{ - 0.29}^{ + 0.33} (stat.) \pm 0.15(syst.\exp .) \hfill \\ \pm 0.05(syst.D**)ps, \hfill \\ \tau (B^0 ) = 1.17_{ - 0.23}^{ + 0.29} (stat.) \pm 0.51(syst.\exp .) \hfill \\ \pm 0.05(syst.D**)ps, \hfill \\ \tau (B^ + )/\tau (B^0 ) = 1.11_{ - 0.39}^{ + 0.51} (stat.) \pm 0.05(syst.\exp .) \hfill \\ \pm 0.10(syst.D**)ps. \hfill \\ \end{gathered} $$
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  • 6
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The OPAL detector at LEP is used to measure the branching ratio of theZ 0 into invisible particles by measuring the cross section of single photon events ine + e − collisions at centre-of-mass energies near theZ 0 resonance. In a data sample of 5.3 pb−1, we observe 73 events with single photons depositing more than 1.5 GeV in the electromagnetic calorimeter, with an expected background of 8±2 events not associated with invisibleZ 0 decay. With this data we determine theZ 0 invisible width to be 0.50±0.07±0.03 GeV, where the first error is statistical and the second systematic. This corresponds to 3.0±0.4±0.2 light neutrino generations in the Standard Model.
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  • 7
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Four-jet final states of hadronicZ 0 decays, observed ine + e − annihilation around 91 GeV centre of mass energy, are analysed in terms of observables that are sensitive to the non-abelian gauge structure of QCD. After correction for detector resolution and fragmentation effects, the data are compared to QCD and also to predictions of the Abelian vector gluon gauge theory. The theoretical expectations are calculated in both second order and leading logarithmic approximation of perturbation theory. The data are compatible with QCD but cannot be described by the predictions of the Abelian vector gluon models. From the measured topological distributions, upper limits for the relative production rates of $$q\bar qq\bar q$$ final states are derived.
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  • 8
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A search for minimal standard model (MSM) and minimal supersymmetric model (MSSM), Higgs bosons with masses larger than 3 GeV/c2 has been performed by the OPAL collaboration one + e − data from LEP corresponding to an integrated luminosity of 1.24 pb−1. The limits for MSM Higgs bosons have been obtained using the channelsZ 0→Z 0* H 0,Z 0*→(v $$\bar v$$ ore + e − or µ+, µ−. The search for MSSM Higgs bosons has been performed using the channelsZ 0→Z 0* H 0,v $$\bar v$$ ore + e − or µ+µ−),h 0 →q $$\bar q$$ andZ 0→h 0 A 0,h 0 A 0→(4 jet orτ + τ −→ or 4τ), whereh 0 andA 0 are the two lightest neutral MSSM Higgs bosons. No Higgs boson signal has been observed. The MSM Higgs boson is excluded in the mass range 3 GeV 〈 $$m_{H^0 }$$ 〈25.3 GeV/c2 at the 95% confidence level; limits on the masses of the two lightest neutral MSSM Higgs bosons are obtained forh 0 mases up to 40.5 GeV/c2.
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  • 9
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Jet production rates in hadronicZ 0 decays are studied using four different recombination schemes to define resolvable jets. The strong coupling constant α s ( $$M_{Z^0 } $$ ) is determined in fits of the correspondingO(α s 2 ) QCD calculations to the differential 2-jet distributionsD 2(y). Hadronisation corrections and renormalisation scale uncertainties are found to be different for each recombination scheme. Within their overall systematic uncertainties, the four schemes yield consistent values of α s ( $$M_{Z^0 } $$ ), leading to a final result of $$\alpha _s (M_{Z^0 } ) = 0.118 \pm 0.008.$$ . The error includes the experimental uncertainties (±0.003), uncertainties of hadronisation corrections and of the degree of parton virtualities to which the data are corrected, as well as the uncertainty of choosing the renormalisation scale.
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  • 10
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We present an analysis of multiplicity distributions of charged particles produced inZ 0 hadronic decays. The results are based on the analysis of 82941 events collected within 100 MeV of theZ 0 peak energy with the OPAL detector at LEP. The charged particle multiplicity distribution, corrected for initial-state radiation and for detector acceptance and resolution, was found to have a mean 〈n ch〉=21.40±0.02(stat.)±0.43(syst.) and a dispersionD=6.49±0.02(stat.)±0.20(syst.). The shape is well described by the Lognormal and Gamma distributions. A negative binomial parameterisation was found to describe the shape of the multiplicity distribution less well. A comparison with results obtained at lower energies confirms the validity of KNO(-G) scaling up to LEP energies. A separate analysis of events with low sphericity, typically associated with two-jet final states, shows the presence of features expected for models based on a stochastic production mechanism for particles. In all cases, the features observed in the data are well described by the Lund parton shower model JETSET.
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