Regional Alterations in Purkinje Cell Density in Patients with Autism
Publication Date
February 24, 2014
Journal
PLOS ONE
Authors
Jerry Skefos, Christopher Cummings, Katelyn Enzer, Jarrod Holiday, et al
Volume
9
Issue
2
Pages
e81255
DOI
https://dx.plos.org/10.1371/journal.pone.0081255
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0081255
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24586223
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933333
Europe PMC
http://europepmc.org/abstract/MED/24586223
Web of Science
000331880700001
Scopus
84897851142
Mendeley
http://www.mendeley.com/research/regional-alterations-purkinje-cell-density-patients-autism-1
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Mendeley | Further Information

{"title"=>"Regional alterations in Purkinje cell density in patients with autism", "type"=>"journal", "authors"=>[{"first_name"=>"Jerry", "last_name"=>"Skefos", "scopus_author_id"=>"11141587600"}, {"first_name"=>"Christopher", "last_name"=>"Cummings", "scopus_author_id"=>"56650100600"}, {"first_name"=>"Katelyn", "last_name"=>"Enzer", "scopus_author_id"=>"56105810800"}, {"first_name"=>"Jarrod", "last_name"=>"Holiday", "scopus_author_id"=>"56105800800"}, {"first_name"=>"Katrina", "last_name"=>"Weed", "scopus_author_id"=>"56106380400"}, {"first_name"=>"Ezra", "last_name"=>"Levy", "scopus_author_id"=>"56105495300"}, {"first_name"=>"Tarik", "last_name"=>"Yuce", "scopus_author_id"=>"56106042200"}, {"first_name"=>"Thomas", "last_name"=>"Kemper", "scopus_author_id"=>"35453198600"}, {"first_name"=>"Margaret", "last_name"=>"Bauman", "scopus_author_id"=>"7007019448"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84897851142", "doi"=>"10.1371/journal.pone.0081255", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24586223", "issn"=>"19326203", "scopus"=>"2-s2.0-84897851142", "pui"=>"372609163"}, "id"=>"2879b582-287d-3aae-8bc4-433dd5c7e648", "abstract"=>"Neuropathological studies, using a variety of techniques, have reported a decrease in Purkinje cell (PC) density in the cerebellum in autism. We have used a systematic sampling technique that significantly reduces experimenter bias and variance to estimate PC densities in the postmortem brains of eight clinically well-documented individuals with autism, and eight age- and gender-matched controls. Four cerebellar regions were analyzed: a sensorimotor area comprised of hemispheric lobules IV-VI, crus I & II of the posterior lobe, and lobule X of the flocculonodular lobe. Overall PC density was thus estimated using data from all three cerebellar lobes and was found to be lower in the cases with autism as compared to controls, an effect that was most prominent in crus I and II (p<0.05). Lobule X demonstrated a trend towards lower PC density in only the males with autism (p = 0.05). Brain weight, a correlate of tissue volume, was found to significantly contribute to the lower lobule X PC density observed in males with autism, but not to the finding of lower PC density in crus I & II. Therefore, lower crus I & II PC density in autism is more likely due to a lower number of PCs. The PC density in lobule X was found to correlate with the ADI-R measure of the patient's use of social eye contact (R(2) = -0.75, p = 0.012). These findings support the hypothesis that abnormal PC density may contribute to selected clinical features of the autism phenotype.", "link"=>"http://www.mendeley.com/research/regional-alterations-purkinje-cell-density-patients-autism-1", "reader_count"=>55, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>2, "Researcher"=>12, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>3, "Student > Master"=>6, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>2, "Researcher"=>12, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>3, "Student > Master"=>6, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>5, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>7, "Neuroscience"=>12, "Design"=>1, "Arts and Humanities"=>1, "Psychology"=>6, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>12}, "Psychology"=>{"Psychology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>5}, "Environmental Science"=>{"Environmental Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>3, "Finland"=>1, "United Kingdom"=>3}, "group_count"=>3}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1396876"], "description"=>"<p>This flatmap diagram displays the four cerebellar regions of interest for our stereological assay. Hemispheric lobules IV–VI (in yellow) are bordered by the preculminate and superior posterior fissures, lateral to the fourth ventricle. Crus I (in blue) is the region bordered by the superior posterior and horizontal fissures. Crus II (in green) is bordered by the horizontal and ansoparamedian fissures. Lobule X, the flocculonodular lobe (in orange), is bordered by the posterolateral fissure. This image is an adaptation of the diagram by Larsell, 1958 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081255#pone.0081255-Larsell2\" target=\"_blank\">[80]</a>.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology", "regions"], "article_id"=>943203, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cerebellar_Regions_Investigated_/943203", "title"=>"Cerebellar Regions Investigated.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396877"], "description"=>"<p>This figure depicts our stereological approach for quantifying PC density in each region of the cerebellum. 2a displays a full sagittal section of the human brain. 2b represents the positioning of contour lines used to select the boundaries around each region of interest, within which sampling occurs. Lobules IV–VI are highlighted in green, crus I is highlighted in pink, crus II is highlighted in blue, and the flocculus of lobule X is highlighted in orange at the bottom of the section. 2c displays a hypothetical placement of counting frames (optical disector probes) within lobules IV–VI. The counting frame size has been increased to aid in visualization for this example. The white dotted line displays the randomly imposed grid over the contour, which regulates the distance between counting frames along the X–Y plane of the section. A counting frame is placed in the top-left of each grid cell if it will include a portion of the region of interest as designated by the contour line. Finally, 2d displays a histological section with an imposed counting frame that includes two PCs to be counted. The use of the optical disector probe dictates that PCs are counted when within the counting frame or at all touching the green line, but never when cells intersect with the red line.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology", "pc"], "article_id"=>943204, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stereological_Assessment_of_PC_Density_/943204", "title"=>"Stereological Assessment of PC Density.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396878"], "description"=>"<p>This graph demonstrates the findings from our linear mixed models (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081255#pone-0081255-t002\" target=\"_blank\">Table 2</a>). Mean PC density was lower in the autism group in each region assayed, but this finding was most prominent in crus I and II (marked with <b>*</b>), where there was 19.8±9% and 21.7±9% lower PC densities, respectively (p = 0.039 and p = 0.032, t-test). (See the results of this test in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081255#pone-0081255-t003\" target=\"_blank\">Table 3</a>). Lobule X PC density was lower in the males with autism (marked with ‡) than in control males (p = 0.05), and lower than female cases in the autism group (p = 0.022). Bars represent mean ± standard deviation. The number of subjects for each test from each diagnostic group and their gender are represented in the results tables (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081255#pone-0081255-t002\" target=\"_blank\">Tables 2</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081255#pone-0081255-t003\" target=\"_blank\">3</a>).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology", "pc"], "article_id"=>943205, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.g003", "stats"=>{"downloads"=>4, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regional_PC_Density_/943205", "title"=>"Regional PC Density.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396880"], "description"=>"<p>Overall PC density obtained from the anterior, posterior, and flocculonodular lobes negatively correlates with age (R<sup>2</sup> = −0.39±0.14, p = 0.030). Some cases were missing data from an individual region (as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081255#s2\" target=\"_blank\">Methods</a>) and were not included: one female and one male case from the autism and control groups were not included.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology", "pc", "decreases"], "article_id"=>943207, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.g004", "stats"=>{"downloads"=>7, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overall_PC_Density_Decreases_with_Age_/943207", "title"=>"Overall PC Density Decreases with Age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396887"], "description"=>"<p>Lobule X PC density in the autism group negatively correlated with ADI-R question 50, which assessed the social and communicative use of eye contact (R<sup>2</sup> = −0.75±0.04, p = 0.012). Higher scores on the ADI-R correspond with increased symptom severity. One case from the autism group was lacking sufficient ADI-R data to be included in this analysis.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology", "pc"], "article_id"=>943208, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.g005", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lobule_X_PC_Density_is_Associated_with_Direct_Gaze_/943208", "title"=>"Lobule X PC Density is Associated with Direct Gaze.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396907"], "description"=>"<p>These figures represent the importance of estimating PC density in 3-dimensional space rather than along a 1-dimensional line (PC/mm<sup>3</sup> rather than PC/mm). 7a and 7b display two views of a 3-dimensional model of a cerebellar folium, in which PCs (black) are arranged in a monolayer apposed to the granule cell layer (blue) that surrounds a central white matter tract (white). 7b displays two slices, one perfectly parallel to a plane of PCs, and the other, more realistically, transverse to this plane. 7c and 7d are cartoons demonstrating the PC arrangement within the parallel and transverse slice, respectively. Notice in 7d the PC layer is thicker, the degree to which depends on the slice position. Also notice that the selection of which PCs lie perfectly along a line is ambiguous (a few examples have been circled in red). This ambiguity introduces human error when performing an estimate of PC/mm that is eliminated in 3-dimensional estimates of PC/mm<sup>3</sup> as are utilized in this study.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology", "pc"], "article_id"=>943211, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.g006", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Models_of_PC_Arrangement_/943211", "title"=>"Models of PC Arrangement.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396914"], "description"=>"<p>This photomicrograph is an illustrative example of the arrangement of PCs on a transverse section. The PCs (purple) go out of focus to the left as the PC layer curves through the depth of the tissue section. The granule cell layer (blue) is visible below the PC layer, the molecular layer surrounds the PC layer (seen here as sparsely stained space), and the white matter tract is out of view to the right. Nissl-stained section from the celloidin collection used in this study, reference bar = 100 µm.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology", "transverse"], "article_id"=>943218, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.g007", "stats"=>{"downloads"=>3, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Photomicrograph_of_Transverse_Section_/943218", "title"=>"Photomicrograph of Transverse Section.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396915"], "description"=>"a<p>Fresh brain weight (in grams) was measured prior to tissue processing.</p>b<p>Postmortem interval.</p>c<p>Mental Retardation.</p>d<p>Left brain hemisphere was investigated. (All other cases were investigated from the right brain hemisphere).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology"], "article_id"=>943219, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_Characteristics_/943219", "title"=>"Clinical Characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396916"], "description"=>"a<p>Met the cutoff for false discovery rate.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology", "differences", "purkinje"], "article_id"=>943220, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.t003", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regional_Differences_in_Purkinje_Cell_Density_/943220", "title"=>"Regional Differences in Purkinje Cell Density.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-24 03:29:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1396917"], "description"=>"a<p>Cells in the table that have bold data presented designate the target results for each variable and interaction, whereas cells with italicized data designate results that are more adequately assessed by a different test presented in the table: Test 1 was designed to investigate the overall effect of gender and autism diagnosis on PC density. It incorporated cerebellar regional volume as a WLS weight to adjust the test's significance relative to the regional volume for each PC density measurement. Test 3 was designed to test the regional differences in PC density as an effect of gender and diagnosis. Tests 2 and 4 are designed to investigate the contribution of fresh brain weight (grams), as a correlate of tissue volume <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081255#pone.0081255-Witelson1\" target=\"_blank\">[39]</a>, to Tests 1 and 3, respectively.</p>b<p>One control male case was missing brain weight information.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Neurological system", "Central nervous system", "neuroanatomy", "histology", "neuroscience", "Developmental neuroscience", "Neurobiology of disease and regeneration", "Diagnostic medicine", "pathology", "anatomical pathology", "neuropathology", "Mental health", "psychology", "Social psychology", "neurology", "Cerebellar disorders", "Cognitive neurology", "pediatrics", "Developmental and pediatric neurology"], "article_id"=>943221, "categories"=>["Biological Sciences", "Medicine", "Sociology"], "users"=>["Jerry Skefos", "Christopher Cummings", "Katelyn Enzer", "Jarrod Holiday", "Katrina Weed", "Ezra Levy", "Tarik Yuce", "Thomas Kemper", "Margaret Bauman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081255.t002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Linear_Mixed_Models_a_/943221", "title"=>"Linear Mixed Models.<sup>a</sup>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-24 03:29:47"}

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