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An association between advanced paternal age at birth and risk for autism spectrum disorders and the underlying biological mechanisms

Research Project

Project/Area Number 20591396
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

TSUCHIYA Kenji  Hamamatsu University School of Medicine, 子どものこころの発達研究センター, 特任准教授 (20362189)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Kaori  浜松医科大学, 子どものこころの発達研究センター, 特任助教 (20447808)
KANAYAMA Naohiro  浜松医科大学, 医学部・産婦人科医学講座, 教授 (70204550)
SUZUKI Katsuaki  浜松医科大学, 子どものこころの発達研究センター, 特任准教授
NAKAMURA Kazuhiko  浜松医科大学, 医学部・精神医学講座, 准教授 (80263911)
MATSUZAKI Hideo  浜松医科大学, 子どものこころの発達研究センター, 特任准教授
TSUJII Masatsugu  中京大学, 現代社会学部, 教授
TAKEI Noriyoshi  浜松医科大学, 子どものこころの発達研究センター, 教授 (80206937)
宮地 泰士  浜松医科大学, 子どものこころの発達研究センター, 特任助教 (60444345)
Co-Investigator(Renkei-kenkyūsha) ITOH Hiroaki  浜松医科大学, 医学部・周産母子センター, 臨床教授
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords自閉症スペクトラム / 言語 / 生殖補助医療 / 疫学 / コホート研究 / 父親 / ロジスティック回帰分析 / 母子手帳
Research Abstract

Background and aim. Paternal age at birth has been suggested to be associated with autism spectrum disorder (ASD). In this study, we aimed at replicating the association in a Japanese sample in a retrospective manner, and at investigating biological mechanisms underlying this association using a birth cohort. A potential candidate for this mechanism is a use of artificial reproductive technique.
Method 1. "Retrospective study" : 84 individuals with high-functioning ASD and 208 typically developed control individuals were enrolled. A statistical association was sought between diagnosis of ASD and paternal age at birth, while controlling for gender, parity, and maternal age at birth.
Method 2. "Prospective study" : 780 pregnant women and their babies were enrolled as a part of an ongoing birth cohort study who were born during the period of 19 November, 2007 and 1 July, 2009. The participating mother-and-child dyads were followed up until the end of 2010 to examine whether any aberrant dev … More elopmental trajectories would be found ; such outcome measures include scores of Mullen Scales of Early Learning, developmental milestones, and suspected diagnosis of ASD. We also examined a risk of suspected ASD in association with paternal age at birth, and artificial reproductive technique as well. Result 1. "Retrospective study" : The association between paternal age at birth and a risk for ASD was confirmed after controlling for covariates. The dose-response relationship was also found.
Result 2. "Prospective study" : In univariate analyses, paternal age at birth did not predict delay in motor/language development, in achievement of developmental milestones, and suspected diagnosis of ASD. On the other hand, artificial reproductive technique appeared to predict delayed development and ASD, although the associations did not reach statistical significance. Due to lack of statistical power, we were unable to seek for interaction between paternal age at birth and artificial reproductive therapy in association with a risk for ASD.
Conclusion. Although firm conclusions are awaited, this study suggested relevance of artificial reproductive techniques as an underlying biological mechanism for the association between paternal age at birth and ASD. Less

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (46 results)

All 2011 2010 2009 2008 Other

All Journal Article (31 results) (of which Peer Reviewed: 9 results) Presentation (10 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Jiko-shisen-kyofu (fear of one's own glance), but not taijin-kyofusho (fear of interpersonal relations), is an east Asian culture-related specific syndrome.2011

    • Author(s)
      Iwata Y, Suzuki K, Takei N, Toulopoulou T, Tsuchiya KJ, Matsumoto K, Takagai S, Oshiro M, Nakamura K, Mori N.
    • Journal Title

      Australian and New Zealand Journal of Psychiatry 45

      Pages: 148-152

    • Related Report
      2010 Final Research Report
  • [Journal Article] Reduced acetylcholinesterase activity in the fusiform gyrus in adults with autism spectrum disorders.2011

    • Author(s)
      Suzuki K, Sugihara G, Ouchi Y, Nakamura K, Tsujii M, Futatsubashi M, Iwata Y, Tsuchiya KJ, Matsumoto K, Takebayashi K, Wakuda T, Yoshihara Y, Suda S, Kikuchi M, Takei N, Sugiyama T, Irie T, Mori N.
    • Journal Title

      Archives of General Psychiatry 68

      Pages: 306-313

    • Related Report
      2010 Final Research Report
  • [Journal Article] 自閉症の疫学研究の動向と出生コホート研究2011

    • Author(s)
      土屋賢治, 松本かおり, 武井教使
    • Journal Title

      日本神経精神薬理学雑誌

      Volume: 31 Pages: 29-34

    • NAID

      10029093979

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder.2010

    • Author(s)
      Iwayama Y, Hattori E, Maekawa M, Yamada K, Toyota T, Ohnishi T, Iwata Y, Tsuchiya KJ, Sugihara G, Kikuchi M, Hashimoto K, Iyo M, Inada T, Kunugi H, Ozaki N, Iwata N, Nanko S, Iwamoto K, Okazaki Y, Kato T, Yoshikawa T.
    • Journal Title

      American Journal of Medical Genetics B Neuropsychiatric Genetics 153B

      Pages: 484-493

    • Related Report
      2010 Final Research Report
  • [Journal Article] Serum levels of platelet-derived growth factor BB homodimers are increased in male children with autism.2010

    • Author(s)
      Kajizuka M, Miyachi T, Matsuzaki H, Iwata K, Shinmura C, Suzuki K, Suda S, Tsuchiya KJ, Matsumoto K, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Takei N, Mori N.
    • Journal Title

      Progress in Neuropsychopharmacology and Biological Psychiatry 34

      Pages: 154-158

    • Related Report
      2010 Final Research Report
  • [Journal Article] Decreased serum levels of adiponectin in subjects with autism.2010

    • Author(s)
      Fujita-Shimizu A, Suzuki K, Nakamura K, Miyachi T, Matsuzaki H, Kajizuka M, Shinmura C, Iwata Y, Suda S, Tsuchiya KJ, Matsumoto K, Sugihara G, Iwata K, Yamamoto S, Tsujii M, Sugiyama T, Takei N, Mori N.
    • Journal Title

      Progress in Neuropsychopharmacology and Biological Psychiatry 34

      Pages: 455-458

    • Related Report
      2010 Final Research Report
  • [Journal Article] Reduced expression of apolipoprotein E receptor type 2 in peripheral blood lymphocytes from patients with major depressive disorder.2010

    • Author(s)
      Suzuki K, Iwata Y, Matsuzaki H, Anitha A, Suda S, Iwata K, Shinmura C, Kameno Y, Tsuchiya KJ, Nakamura K, Takei N, Mori N.
    • Journal Title

      Prog Neuropsychopharmacol Biol Psychiatry 34

      Pages: 1007-1010

    • Related Report
      2010 Final Research Report
  • [Journal Article] Brain seronin and dopamine transporter bindings in adults with high-functioning autism.2010

    • Author(s)
      Nakamura K, Sekine Y, Ouchi Y, Tsujii M, Yoshikawa E, Futatsubashi M, Tsuchiya KJ, Sugihara G, Iwata Y, Suzuki K, Matsuzaki H, Suda S, Sugiyama T, Takei N, Mori N.
    • Journal Title

      Archives of General Psychiatry 67

      Pages: 59-68

    • Related Report
      2010 Final Research Report
  • [Journal Article] Searching for very early precursors of autism spectrum disorders : the Hamamatsu Birth Cohort for Mothers and Children (HBC).2010

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Suda S, Miyachi T, Itoh H, Kanayama N, Hirano K, Ohzeki T, Takei N, the HBC Study Team.
    • Journal Title

      Journal of Developmental Origins of Health and Disease 1

      Pages: 158-173

    • Related Report
      2010 Final Research Report
  • [Journal Article] Further evidence for the role of MET in autism susceptibility.2010

    • Author(s)
      Thanseem I, Nakamura K, Miyachi T, Toyota T, Yamada S, Tsujii M, Tsuchiya KJ, Anitha A, Iwayama Y, Yamada K, Hattori E, Matsuzaki H, Matsumoto K, Iwata Y, Suzuki K, Suda S, Kawai M, Sugihara GI, Takebayashi K, Takei N, Ichikawa H, Sugiyama T, Yoshikawa T, Mori N.
    • Journal Title

      Neuroscience Research 68

      Pages: 137-141

    • Related Report
      2010 Final Research Report
  • [Journal Article] Asperger's Syndromeを含むAutism Spectrum Disorders(ASD)のスクリーニングと診断補助尺度・面接法2010

    • Author(s)
      松本かおり, 土屋賢治
    • Journal Title

      精神科

      Volume: 16 Pages: 32-40

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 浜松母と子の出生コホート(HBC):子どもの発達の新しい理解に向けて2010

    • Author(s)
      土屋賢治, 松本かおり, 武井教使
    • Journal Title

      脳21

      Volume: 13 Pages: 155-160

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Searching for very early precursors of autism spectrum disorders : the Hamamatsu Birth Cohort for Mothers and Children(HBC).2010

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Suda S, Miyachi T, Itoh H, Kanayama N, et al.
    • Journal Title

      Journal of Developmental Origins of Health and Disease

      Volume: 1 Pages: 158-173

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased serum levels of adiponectin in subjects with autism2010

    • Author(s)
      Fujita-Shimizu A, Suzuki K, Nakamura K, Miyachi T, Matsuzaki H, Kajizuka M, et al.
    • Journal Title

      Prog Neuropsychopharmacol Biol Psychiatry (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain serotonin and dopamine transporter bindings in adults with high- functioning autism2010

    • Author(s)
      Nakamura K, Sekine Y, Ouchi Y, Tsujii M, Yoshikawa E, Futatsubashi M, et al.
    • Journal Title

      Arch Gen Psychiatry 67

      Pages: 59-68

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Searching for very early precursors of autism spectrum disorders : the Hamamatsu Birth Cohort for Mothers and Children (HBC)2010

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Suda S, Miyachi T, Itoh H, Kanayama N, et al
    • Journal Title

      Journal of Developmental Origins of Health and Disease (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolite alterations in the hippocampus of high-functioning adult subjects with autism.2009

    • Author(s)
      Suzuki K, Nishimura K, Sugihara G, Nakamura K, Tsuchiya KJ, Matsumoto K, Takebayashi K, Isoda H, Sakahara H, Sugiyama T, Tsujii M, Takei N, Mori N.
    • Journal Title

      International Journal of Neuropsychopharmacology 13

      Pages: 529-534

    • NAID

      120005305395

    • Related Report
      2010 Final Research Report
  • [Journal Article] 自閉症・自閉症スペクトラム障害の疫学研究の動向2009

    • Author(s)
      土屋賢治, 松本かおり, 武井教使
    • Journal Title

      脳と精神の医学 20

      Pages: 295-302

    • NAID

      10028262617

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Paternal age at birth and high-functioning autism spectrum disorder in the offspring.2008

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Miyachi T, Tsujii M, Nakamura K, Takagai S, Kawai M, Yagi A, Iwaki K, Suda S, Sugihara G, Iwata Y, Matsuzaki H, Sekine Y, Suzuki K, Sugiyama T, Mori N, Takei N.
    • Journal Title

      British Journal of Psychiary 193

      Pages: 316-321

    • Related Report
      2010 Final Research Report
  • [Journal Article] Serum levels of P-selectin in men with high-functioning autism.2008

    • Author(s)
      Iwata Y, Tsuchiya KJ, Mikawa S, Nakamura K, Takai Y, Suda S, Sekine Y, Suzuki K, Kawai M, Sugihara G, Matsuzaki H, Hashimoto K, Tsujii M, Sugiyama T, Takei N, Mori N.
    • Journal Title

      British Journal of Psychiary 193

      Pages: 338-339

    • Related Report
      2010 Final Research Report
  • [Journal Article] Distinguishing broad autism phenotype from schizophrenia-spectrum disorders.2008

    • Author(s)
      Sugihara G, Tsuchiya KJ, Takei N.
    • Journal Title

      Journal of Autism and Developmental Disorders 38

      Pages: 1998-1999

    • Related Report
      2010 Final Research Report
  • [Journal Article] Voxel-based structural magnetic resonance imaging (MRI) study of patients with early onset schizophrenia.2008

    • Author(s)
      Yoshihara Y, Sugihara G, Matsumoto H, Suckling J, Nishimura K, Toyoda T, Isoda H, Tsuchiya KJ, Takebayashi K, Suzuki K, Sakahara H, Nakamura K, Mori N, Takei N.
    • Journal Title

      Annals of General Psychiatry 7

      Pages: 25-25

    • NAID

      120005314220

    • Related Report
      2010 Final Research Report
  • [Journal Article] Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine-induced hyperlocomotion in adulthood.2008

    • Author(s)
      Wakuda T, Matsuzaki H, Suzuki K, Iwata Y, Shinmura C, Suda S, Iwata K, Yamamoto S, Sugihara G, Tsuchiya KJ, Ueki T, Nakamura K, Nakahara D, Takei N, Mori N.
    • Journal Title

      PLoS One 3

    • Related Report
      2010 Final Research Report
  • [Journal Article] Paternal age at birth and high-functioning autistic-spectrum disorder in offspring2008

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Miyachi T, Tsujii M, Nakamura K, et al.
    • Journal Title

      British Journal of Psychiatry 193

      Pages: 316-321

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum levels of P-selectin in men with high- functioningautism2008

    • Author(s)
      Iwata Y, Tsuchiya KJ, Mikawa S, Nakamura K, Takai Y, Suda S, et al.
    • Journal Title

      British Journal of Psychiatry 193

      Pages: 338-339

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine induced hyperlocomotion in adulthood2008

    • Author(s)
      Wakuda T, Matsuzaki H, Suzuki K, Iwata Y, Shinmura C, Suda S, et al.
    • Journal Title

      PLoS ONE 3

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 滅人期アスペルガー症候群のADI-R (自閉症診断面接改訂版)による診断2008

    • Author(s)
      中村和彦, 土屋賢治, 八木敦子, 松本かおり, 宮地泰士, 辻井正次, ほか
    • Journal Title

      精神医学 50

      Pages: 787-799

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease.

    • Author(s)
      Yokokura M, Mori N, Yagi S, Yoshikawa E, Kikuchi M, Yoshihara Y, Wakuda T, Sugihara G, Takebayashi K, Suda S, Iwata Y, Ueki T, Tsuchiya KJ, Suzuki K, Nakamura K, Ouchi Y.
    • Journal Title

      European Journal of Nuclear Medicine and Molecular Imaging in press.

    • Related Report
      2010 Final Research Report
  • [Journal Article] Replication study of Japanese cohorts supports the role of STX1A in autism susceptibility.

    • Author(s)
      Nakamura K, Iwata Y, Anitha A, Miyachi T, Toyota T, Yamada S, Tsujii M, Tsuchiya KJ, Iwayama Y, Yamada K, Hattori E, Matsuzaki H, Matsumoto K, Suzuki K, Suda S, Takebayashi K, Takei N, Ichikawa H, Sugiyama T, Yoshikawa T, Mori N.
    • Journal Title

      Progress in Neuropsychopharmacology and Biological Psychiatry in press.

    • Related Report
      2010 Final Research Report
  • [Journal Article] Age-specific 3-month cumulative incidence of postpartum depression : The Hamamatsu Birth Cohort Study (HBC).

    • Author(s)
      Matsumoto K, Tsuchiya KJ, Itoh H, Kanayama N, Suda S, Matsuzaki H, Iwata Y, Suzuki K, Nakamura K, Mori N, Takei N.
    • Journal Title

      Journal of Affective Disorders in press.

    • Related Report
      2010 Final Research Report
  • [Journal Article] Age-specific 3-month cumulative incidence of postpartum depression : The Hamamatsu Birth Cohort Study(HBC).

    • Author(s)
      Matsumoto K, Tsuchiya KJ, Itoh H, Kanayama N, Suda S, et al.
    • Journal Title

      Journal of Affective Disosrders

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Early- and late-onset postpartum depression and the associated risk factors : the HBC Study2010

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Takahashi S, Mori T, et al.
    • Organizer
      5th Conference for Epidemiological Longitudinal Studies in Europe
    • Place of Presentation
      Paphos, Cyprus
    • Year and Date
      2010-10-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Postpartum depression and prepregnancy BMI : the HBC Study2010

    • Author(s)
      Mori T, Tsuchiya KJ, Matsumoto K, Muraki H, et al.
    • Organizer
      5th Conference for Epidemiological Longitudinal Studies in Europe
    • Place of Presentation
      Paphos, Cyprus
    • Year and Date
      2010-10-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Mother's unintended pregnancy associated with lower ponderal index at 4 months of the infant : the HBC Study2010

    • Author(s)
      Takahashi S, Tsuchiya KJ, Matsumoto K, Mori T, et al.
    • Organizer
      5th Conference for Epidemiological Longitudinal Studies in Europe
    • Place of Presentation
      Paphos, Cyprus
    • Year and Date
      2010-10-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Postpartum depression and prepregnancy BMI : the HBC Study.2010

    • Author(s)
      Mori T, Tsuchiya KJ, Matsumoto K, Muraki H, Takahashi S, Takabayashi R, Suzuki Y, Sato R, Narumiya M, Takei N, the HBC Study Team.
    • Organizer
      Longitudinal and Life Course Studies 1 (suppl 3) : 372
    • Place of Presentation
      [conference proceeding]
    • Related Report
      2010 Final Research Report
  • [Presentation] Mother's unintended pregnancy associated with lower ponderal index at 4 months of the infant : the HBC Study.2010

    • Author(s)
      Takahashi S, Tsuchiya KJ, Matsumoto K, Mori T, Takabayashi R, Suzuki Y, Sato R, Narumiya M, Seno Y, Suda S, Matsuzaki H, Suzuki K, Mori N, Takei N, the HBC Study Team.
    • Organizer
      Longitudinal and Life Course Studies 1 (suppl 3) : 373
    • Place of Presentation
      [conference proceeding]
    • Related Report
      2010 Final Research Report
  • [Presentation] Early-and late-onset postpartum depression and the associated risk factors : the HBC Study.2010

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Takahashi S, Mori T, Takabayashi R, Suzuki Y, Sato R, Narumiya M, Seno Y, Suda S, Matsuzaki H, Suzuki K, Mori N, Takei N, the HBC Study Team.
    • Organizer
      Longitudinal and Life Course Studies 1 (suppl 3) : 374
    • Place of Presentation
      [conference proceeding]
    • Related Report
      2010 Final Research Report
  • [Presentation] Searching for causes and effects of an increase in LBW children in Japan : The Hamamatsu Birth Cohort for Mothers and Children (HBC).2009

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Miyachi T, Tsujii M, Itoh H, Kanayama N, Hirano K, Ohzeki T, Takei N, the HBC Study Team, the Hamamatsu DOHaD Study Team.
    • Organizer
      The 6th World Congress on Developmental Origins of Health and Disease
    • Place of Presentation
      Santiago de Chile
    • Related Report
      2010 Final Research Report
  • [Presentation] Unwanted pregnancy and its detrimental effect on early language development in the offspring : the HBC Study.2009

    • Author(s)
      Matsumoto K, Tsuchiya KJ, Miyachi T, Itoh H, Kanayama N, Takei N, the HBC Study Team.
    • Organizer
      The 6th World Congress on Developmental Origins of Health and Disease
    • Place of Presentation
      Santiago de Chile
    • Related Report
      2010 Final Research Report
  • [Presentation] Validating a Japanese version of the Ritvo Autism and Asperger's Diagnostic Scale : a pilot study.2008

    • Author(s)
      Matsumoto K, Tsuchiya KJ, Ritvo ER, Tsujii M.
    • Organizer
      The 8th International Meeting for Autism Research
    • Place of Presentation
      London
    • Related Report
      2010 Final Research Report
  • [Presentation] Advanced paternal age associated with an increased risk for autism spectrum disorder.2008

    • Author(s)
      Tsuchiya KJ, Matsumoto K, Takagai S, Kawai M, Nakamura K, Suda S, Tsujii M, Miyachi T, Mori N, Takei N.
    • Organizer
      The 18^<th> Congress for International Association for Epidemiology
    • Place of Presentation
      Porto Alegre
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://rccmd.org/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://rccmd.org/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://rccmd.org/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://rccmd.org

    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 自閉症の診断薬2011

    • Inventor(s)
      橋本謙二, 伊予雅臣, 森則夫, 武井教使, 三辺義雄, 中村和彦, 岩田泰秀, 関根吉統, 土屋賢治, 辻井正次
    • Industrial Property Rights Holder
      橋本謙二, 伊予雅臣, 森則夫, 武井教使, 三辺義雄, 中村和彦, 岩田泰秀, 関根吉統, 土屋賢治, 辻井正次
    • Acquisition Date
      2011-02-10
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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