- Open Access
Convergent genetic linkage and associations to language, speech and reading measures in families of probands with Specific Language Impairment
© The Author(s) 2009
- Received: 23 June 2008
- Accepted: 5 August 2009
- Published: 26 August 2009
We analyzed genetic linkage and association of measures of language, speech and reading phenotypes to candidate regions in a single set of families ascertained for SLI. Sib-pair and family-based analyses were carried out for candidate gene loci for Reading Disability (RD) on chromosomes 1p36, 3p12-q13, 6p22, and 15q21, and the speech-language candidate region on 7q31 in a sample of 322 participants ascertained for Specific Language Impairment (SLI). Replication or suggestive replication of linkage was obtained in all of these regions, but the evidence suggests that the genetic influences may not be identical for the three domains. In particular, linkage analysis replicated the influence of genes on chromosome 6p for all three domains, but association analysis indicated that only one of the candidate genes for reading disability, KIAA0319, had a strong effect on language phenotypes. The findings are consistent with a multiple gene model of the comorbidity between language impairments and reading disability and have implications for neurocognitive developmental models and maturational processes.
- Gene linkage
- Language, reading, speech phenotypes
- Language impairments
- Specific language impairment
- Gene associations
Although there has been substantial progress recently in the genetics of language impairment and there is strong support for localization to candidate regions on chromosomes 16 and 19 [1–3], the search for candidate genes remains inconclusive  with the exception of a recently identified candidate, CNTNAP2 . In contrast, candidate genes are identified for the closely related clinical conditions of Speech Sound Disorder (SSD) and Reading Disability/Dyslexia (RD), including ROBO1, DCDC2, KIAA0319, and DYX1C1 . A significant limitation of the available studies is that the evidence for overlapping genetic etiology is emerging from different samples, ascertained by SSD or RD, with investigations of single dimension phenotypes per sample. One exception is a recent study  which investigated multiple phenotypes in a sample ascertained for language impairment using a multivariate variance-components approach to define phenotypes. This study focused on two quantitative trait loci (QTLs) on chromosomes 16q (SLI1) and 19q (SLI2). The authors reported different effects for the two QTLs, such that SLI1 had equally strong effects on a non-word repetition phenotype as on reading and spelling phenotypes, while SLI2 influenced non-word repetition and language phenotypes but not literacy phenotypes. The outcomes draw attention to the need for investigations of possible overlapping gene effects in the domain of language and literacy. In the study reported here we pursue possible overlap of language impairment, SSD, and RD with the sites linked to SSD and RD in a sample of children ascertained as language impaired using concurrent measurements of language, speech and reading abilities for probands, siblings, and other family members.
Specific Language Impairment (SLI) is a condition characterized by late emerging and protracted language acquisition relative to age expectations, without intellectual disability, autism diagnosis, hearing loss, or other obvious contributing conditions. The prevalence is estimated as 7% of 6-year-old children . The impairments involve both receptive and expressive language and include late talking and deficits in grammar, vocabulary and discourse . There is a significant effect on a child’s ability to communicate. Although some of the problems appear to resolve with age, other difficulties persist. Recent evidence has shown that children who are late talkers are at higher risk for continued language problems, particularly in syntax . If the condition is not resolved by school age, children are not likely to “outgrow” it. Instead, language impairments are likely to remain into adolescence and adulthood [11–13].
Twin-based heritabilities of between 0.50 and 0.97 have been reported for measures of SLI [14, 15], particularly in populations which sought therapy . Family aggregation studies document increased risk for SLI among siblings and parents of affected children. Twenty-two percent of nuclear family members of SLI probands are reported with a positive history compared to 7% of control families , with a similar range of affectedness across studies [18, 19].
Recent linkage studies from the SLI Consortium of Great Britain [1, 2] report genome-wide linkage screens of quantitative measures of language that implicate chromosomes 16q (SLI1) and 19q (SLI2). A follow-up study confirmed linkage to chromosomes 16 and 19 in a subset of the SLI Consortium full sample.
Based on the finding that a complex speech-language disorder is due to mutation in the FOXP2 gene on chromosome 7q , this gene became a candidate for SLI. Microsatellite markers in the FOXP2 gene and surrounding region yielded association with one of the markers about 5 Mb proximal to the gene as well as one marker in the CFTR gene, distal to FOXP2 . Further study of the SLI Consortium identified a down-stream regulatory effect of the FOXP2 gene on chromosome seven on the CNTNAP2 neurexin gene that in turn is known to regulate cortical development  and has been linked to late appearance of first words in a sample of children with autism .
Interpretation of these advances requires consideration of the behavioral phenotypes of the linkage studies. Language is multidimensional and various measures are utilized in the investigations to date. With the exception of the investigation of Monaco and colleagues , the phenotypes have been examined unidimensionally. Omnibus language assessments are full-scale tests that include items across multiple dimensions, adjusted for age expectations. Such broad measures are often used to define probands as well as the phenotype in linkage studies. For example, the SLI Consortium studies used the Clinical Evaluation of Language Fundamentals (CELF) test . Two other more narrowly defined phenotypes are of interest; one is an index of morphosyntax in the domain of tense-marking (TNS) and the second is performance on non-word repetition tasks (NWR). Tense-marking and non-word repetition performance have been identified as strong candidates for clinical markers . Significant heritability in twins is reported for NWR and TNS  with a tense marking task originally developed in the lab of Rice as an experimental precursor to a standardized test  The SLI Consortium used another experimental TNS task . Non-word repetition tasks are measures of phonological short-term memory that have been suggested as “core deficits” in SLI  or as a “key contributory trait of SLI”  . The SLI Consortium has consistently used an experimental task . More recently, Bishop  cautions that the evidence for non-word repetition deficit as a cause of syntactic deficits (such as the TNS marker) is quite limited; she proposes instead that if both abilities are weak then language impairment is more likely to be evident. Recent studies [3–5]treat non-word repetition as an endophenotype that functions as a marker of SLI when language impairments are not present.
Most studies of genotype/phenotype correspondence in linkage and association analyses reported to date focus on SLI1 and SLI2, with mixed outcomes for phenotypes. The SLI consortium  found linkage for SLI1 for NWR and linkage for SLI2 for a CELF measure, outcomes replicated with a second cohort of families  . Falcaro et al used the Manchester sample portion of the SLI Consortium, highlighting linkage to SLI1 for nonword rep (N = 33 families) and to SLI2 for TNS (N = 32 families). Results were less strong for the CELF measure (N = 24 for SLI1 and N = 23 for SLI2). Vernes et al detected CNTNAP2-related associations with an omnibus language assessment phenotype (CELF) as well as NWR in 184 families. Although these phenotypes are clearly promising, other phenotypes are also of interest and could clarify genetic effects.
The condition of SLI is related to speech and reading phenotypes. Speech sound disorder (SSD) is characterized by deficits in articulation, phonological processing, and in the cognitive representation of language. This diagnosis excludes cases of speech dyspraxia, identified as part of the FOXP2 phenotype on chromosome 7 [20, 32], although in practice this distinction is not always made, and study populations may include both SSD and dyspraxia . This heterogeneity can complicate efforts to measure genetic influence and localize genes. For example, speech problems are often included within clinical cases of SLI, and as noted above, there is evidence that heritability estimates are increased when probands are ascertained through clinical referral for speech problems . An epidemiologically ascertained sample  yielded a prevalence of SSD as 3.8% of 6-year-old children; of the children with speech delay, an average of 0.51% met the SLI diagnostic criteria. When indexed by SLI, 15% of boys and 11% of girls showed SSD. The overlap is somewhat higher in children who have language impairments with lower levels of nonverbal cognitive performance (15% for boys and 28% of girls). In studies of children ascertained for SSD, findings link this condition to dyslexia-related loci on chromosomes 3, 6 and 15, with suggestive links to chromosome 1 [35–38].
Reading impairments are also related to SLI and SSD. Catts  reports about 50% of children with language impairment have subsequent reading impairments. The relationship of reading and language abilities changes over time. The early stages of reading development involve rapid improvement in word recognition skills, which are associated with phonological processing abilities including nonword repetition ability. The later stages involve the development of text comprehension which is associated with language comprehension abilities [40, 41]. Nonword repetition ability is also related to the reading phenotype, interpreted as an index of verbal memory thought to influence the learning processes for reading as well as language acquisition. Genetic studies have also illustrated the overlap between reading and SLI with the finding of linkage of a reading discrepancy phenotype to chromosome 13q21 in families ascertained for SLI [42, 43].
Reading disability has high heritabilities and segregation analyses have estimated that there are several major loci involved [44, 45]. Linkage analyses identified at least eight regions [6, 46, 47], particularly on chromosomes 15q (DYX1; ), 6p (DYX2; [49–52], 2p (DYX3; , 3p (DYX5; , and 1p (DYX8; [55–57]. In addition, SSD has also shown linkage to markers in DYX1 , DYX2 , and DYX5 regions ; , suggesting common genetic influences. Candidate genes for reading disability have been proposed for several of these loci: MRPL19/C2ORF3 for chromosome 2 , ROBO1 for chromosome 3 , DCDC2 and KIAA0319 on chromosome 6 [60–63], and DYX1C1 on chromosome 15 . At least four of these genes have a role in neuronal or axonal migration in the CNS [59, 61, 62, 65].
The findings of multiple and shared linkages for RD and SSD are consistent with multi-gene influences on language phenotypes. These findings in turn have inspired theoretical multi-gene models for complex cognitive traits. Galaburda et al  posit that multiple genes contribute to reading disability in a complex interaction of genetics, developmental brain changes, and perceptual and cognitive effects associated with dyslexia. They note that although common genetic factors are expected for dyslexia and language impairment, no overlaps have yet been detected. Similarly, Pennington  posits a “probabilistic, multiple cognitive deficit” model with shared cognitive factors and pleiotropic genes and other influences that determine the phenotypic outcome. In contrast, Kovas and Plomin  propose a “generalist gene” hypothesis which stipulates that there are very many genes that affect cognitive development, each with small effects, and their interactions with environmental factors determine the resulting phenotype. Under this model, detection of the individual genes would be difficult without very large sample sizes. This hypothesis stands in contrast to the results of segregation analyses cited above, however, which have supported a more oligogenic hypothesis.
To date, one study  has examined language and reading phenotypes in the same sample ascertained for SLI. This study reports a multivariate linkage analysis of SLI with the SLI Consortium database, with phenotypes consisting of eight scores from a language omnibus test as multiple linguistic phenotypes, three measures of reading/spelling, and a measure of nonword repetition ability. Multivariate analyses provided further support for SLI1 and SLI2 loci, with additional complexities. The conclusion is that their findings “implied that the effect of SLI1 on non-word repetition was equally strong on reading and spelling phenotypes. In contrast, SLI2 appears to have influences on a selection of expressive and receptive language phenotypes in addition to non-word repetition, but did not show linkage to literacy phenotypes” (p. 660).
The principal aims of this investigation were to explore linkage and association of language, speech and reading phenotypes to previously identified QTLs and genes linked to SSD and RD. We aim to replicate previous linkage and association findings for SSD and RD, determine if the linkages extend to SLI diagnostic phenotypes as well, and, if so, to identify new candidates for linkages and associations for SLI.
A total of 322 participants, including 86 probands, 134 siblings, and 102 parents and other relatives were drawn from an ongoing longitudinal study of Specific Language Impairment. The study was approved by the institutional review boards at the University of Kansas and at the University of Nebraska Medical Center. Appropriate informed consent was obtained from the subjects. There were 86 probands, mean ages 6;1 to 8;10 across variables, ascertained from school speech pathology caseloads followed by assessment to meet the requirements of the study. There were a total of 134 siblings: 77 males, mean age 8;6; 57 females, mean age 8;5. Previous studies report longitudinal outcomes for part of this sample, documenting that the children’s language impairments persist into adolescence [13, 69–72].
Probands met four entrance screening criteria. The first was nonverbal intelligence above 85. For children ages 3;6 to 6;11 it was measured with the Columbia Mental Maturity Scales  and for children ages 7–17, the performance IQ scales from the Wechsler Intelligence Test for Children  were utilized. Parents and children ages 17 years and older were evaluated with the performance scales for the Wechsler Intelligence Test for Adults . Probands met exclusionary criteria for nonverbal intelligence; this requirement was not met for parents and siblings whose intellectual status was an outcome of the study. The second criterion for the probands was normal hearing acuity. The third was no history of neurological disorders or diagnosis of autism. The fourth was intelligible speech sufficient for language transcription and production of target phonemes used in word final morphology, as in “goes” and “talks.” Probands were identified as SLI based on language performance one standard deviation or more below the mean on an age appropriate language test. All probands were screened for articulation to ensure they could produce the phonemes needed for morphological measurement and sufficient intelligibility for reliable spontaneous language transcription. Family members received age appropriate speech, language, and reading assessments. Siblings were recruited from age 2 years to adulthood. Within age levels, all participants received the same assessments. The probands and siblings received multiple times of measurement as part of the longitudinal study. For the phenotyping in this study, the lowest value of each variable of interest was selected. This is in keeping with the methods used in the SLI Consortium studies where past or current language performance was used to identify probands . Further, the lowest performance estimate captures the late talker status of siblings.
The phenotypes assessed the following traits for speech, language, reading, and the related area of nonword repetition. For children ages 2;6 to 9 years, speech was measured by the Goldman Fristoe Test of Articulation (GFTA) standard score . Language was subdivided into three dimensions. The first, general language skills, was measured by an omnibus standardized language test appropriate for the individual’s age (Omnibus): for children at or under age 2;6, Preschool Language Scale-3  Total Language Score; ages 2;6–3;11, the Test of Early Language Development-3rd edition, Spoken Language Standard Score ; ages 4–6;11, the Test of Language Development-2: Primary Spoken Language Standard Score; ages 7–17 + , Clinical Evaluation of Language Fundamentals-3rd edition Total Language Standard Score (or Expressive Language Score if that is the only one available) . The second language dimension was Vocabulary: ages 2;6-adults was assessed with the Peabody Picture Vocabulary Test-Revised or 3rd edition (PPVT) [81, 82]. The third language dimension was early spontaneous speech production (mean length of utterance, MLU): for children ages 2;6–10 years of age, the Mean Length of Utterance was computed with the Systematic Analysis of Language Transcripts, with z scores calculated from the norms provided by Leadholm & Miller . Finally, the construct of TNS was evaluated in children ages 3–9 years of age on the Test of Early Grammatical Impairment (TEGI)  . An experimental version of two of the subtests of TEGI were used in the twin study of Bishop and colleagues .
Reading was subdivided into word level reading and comprehension/text reading. Word level reading for children (beginning with children enrolled in kindergarten) through adulthood was measured by the Woodcock Reading Mastery Tests-Revised  Letter Identification (to 9 years only), Word Identification and Word Attack (from kindergarten to adulthood) standard scores. Two quantitative indices were used, one a standard score adjusted for age expectations (WRMT) and one a raw score adjusted to an interval scale benchmarked to fifth grade reading levels (WRMT-w). Beginning at age 7 into adulthood, text reading was assessed with the Gray Oral Reading Test (GORT)  standard scores.
Following earlier precedents, a related processing phenotype, nonword repetition, was included. Beginning at age 4 years into adulthood, nonword repetition was assessed with the Comprehensive Test of Phonological Processing subtest (CTOPP)  standard score.
In addition to the quantitative phenotypes for these tests, categorical phenotypes were also determined with a criterion of standard score of one standard deviation or more below the mean as cut-offs for affected status for each phenotype.
Percent of participants affected by age group: probands, siblings, and parents
MLU z score
MLU z score
Pair counts for each quantitative phenotype
Microsatellite marker location and heterogeneity
Rutgers genetic map (cM)
NCBI physical map (MB)
Fluorescent labeled primers for the selected markers were obtained from Applied Biosystems (Foster City, CA) or IDT (Coralville, IA) and genotyping was done on an AB 3730 DNA Analyzer (Applied Biosystems, Foster City, CA). Allele calls were reviewed by two experienced technologists and were checked for inheritance and recombination errors using the programs GAS  and MERLIN . Any markers with unresolvable genotypes were re-run and re-evaluated or eliminated from the analysis.
Heritability estimates were calculated using the variance components function in MERLIN. Some caveats apply. Reliability is affected by the small, selected samples, and distributional properties of some of the variables. The heritabilities for the standard scores are: GFTA, 96.05%; Woodcock 62.86%; GORT 18.08%; MLU 23.97%; Omnibus score 30.01%; CTOPP 14.83%; PPVT 22.76%; TEGI 19.30%. We note that these are in the range reported for the variables of ).
Linkage was performed with quantitative and categorical measures using the MERLIN package of programs . The MERLIN-regress program was used for the quantitative measures, and the MERLIN nonparametric linkage method was used for affected status for the same measures. These two methods were selected because the quantitative method should have more power to detect linkage across the range of severity, but the categorical measures may highlight genetic differences between clinically affected vs. unaffected individuals. This approach was also applied in previous linkage studies . Interval linkage analysis was used for both methods, with steps of 0.5 cM, and results are expressed as LOD scores as well as p-values.
To verify the results of the MERLIN analyses on a separate platform, the same quantitative phenotypes were analyzed for linkage using the DeFries-Fulker Augmented analysis as implemented in the SAS macro QMS2 . Both of these methods are optimal for families in which probands are selected but siblings are not highly discordant. We performed the two types of analysis as a check for false positive linkages, assuming that true linkages would be detected regardless of analysis platform. For the DeFries-Fulker analysis, linkage was only performed at the marker loci, and the analysis only includes sib-pairs and; the results were reported as p values.
We looked at eight different phenotypes in these studies, two which largely measure reading (Woodcock and GORT), one which measures articulation (GFTA), and five which examine facets of language (MLU, TEGI, CTOPP, PPVT and the Omnibus language score). The reading and articulation phenotypes were used for replication of the linkages of dyslexia and speech sound disorder in our population. The language phenotypes, which were correlated with the other phenotypes in this population (see Table 2), were selected to determine if the linkages extended to SLI diagnostic phenotypes as well. While this gives us a comprehensive view of the phenotypes that may be linked to these regions, we must acknowledge that the multiple tests make it difficult to interpret our overall significance levels. Except where noted, all p-values reported in this study are nominal p-values, not corrected for multiple testing. Because the phenotypes analyzed are all correlated, and the linkage or association tests should be consistent, a Bonferroni correction would be too conservative. Therefore, for the MERLIN analyses we have reported LOD scores, and for the largest LOD scores we have provided nominal p-values, as well as empirical p-values, based on simulations under the null hypothesis.
To determine the empirical significance of the p-values, repeated simulations were performed for all markers and phenotypes across each chromosome using the simulation function in MERLIN and MERLIN-regress. This procedure uses permutations of genotypes simulated under the null hypothesis, while maintaining phenotypes and family structure. The number of simulations for each chromosome was adjusted to obtain at least 500 representations of the highest LOD score for that chromosome. Based on these calculations, between 1000 and 4000 simulations were performed for each chromosomal region, generating more than 400,000 observations for each phenotype.
Based on the results of the linkage, we decided to test three known candidate genes for association with a battery of SNP markers. We genotyped 53 SNPs covering the candidate genes DCDC2 and KIAA0319 on chromosome 6p22 and the FOXP2 region of chromosome 7. SNPs were selected which tag regions of linkage disequilibrium using the Tagger function on HapMap (URL), along with SNPs selected to replicate previously reported associations and haplotypes with RD. In all, 36 SNPs were genotyped on chromosome six spanning the genes DCDC2, KIAA0319, and TTRAP. On chromosome 7, we genotyped 17 SNPs spanning FOXP2, including the region upstream of the gene. Although we found minimal linkage to this gene in our sample, the linkage of this region with SLI  and identification of mutations in dyspraxia ;  made it a candidate. Only quantitative traits were used in this analysis, and analysis was again done by two methods: QTDT  and FBAT . The same quantitative measures were used as in the linkage analyses. Genotyping was done on a Sequenom MassArray iPlex system. While replication of associated SNPs would verify a relationship between disorders at an etiologic level, it is possible that the disorder that is manifested is due to different allelic mutations which would have different associated SNPs. In this case, the patterns of association among individuals selected for SLI, SSD, or RD could serve as a method of “triangulating” on the causal genes.
Chromosome 6 SNP associations
Chromosome 7 SNP associations
This study considers the question of whether regions known to influence RD or SSD also affect related language phenotypes. The results of the linkage and association analyses indicate that it is highly likely that loci exist in the candidate regions that influence language ability, and not just RD or SSD. Linkage analysis does not have the precision to confirm that the same genes in these regions are involved, however. For that reason, association analysis of SNP markers was subsequently done. The SNP association analyses, in an unprecedented finding, point to KIAA0319 as a gene of interest for pleiotropic effects on omnibus language ability, speech impairments, and text comprehension. This common genetic influence is consistent with the pattern of correlations reported in Table 2. The correlation of the omnibus language score and the text comprehension measure (GORT) is high, r = .70, p < .01; the correlation of the speech (GFTA) and reading measure (GORT) is also high, r = .657, p < .01. It should be noted that a vocabulary measure (PPVT) also yielded high correlations with GORT, r = .718, p < .01, with a significant association with one SNP location on KIAA0319. Although the vocabulary association is a weak signal, it is of interest because vocabulary level is a likely mediator of a language effect on text comprehension. Overall, these findings are congruent with investigations of children identified as “poor comprehenders” that report a strong relationship of language impairments and text comprehension performance [105, 106]. In short, the role of KIAA0319 in contributing to the observed overlap of SSD, language impairments and text comprehension warrants further investigation. Other genes or variants in this or other chromosomal regions, not tested in the current work, may also contribute to the shared genetic factors among these speech, reading and language skills.
This is the first evidence of KIAA0319’s possible effect on general language impairment. This finding adds to the earlier reports from the SLI consortium for linkage of chromosomes 16 and 19 to performance on the CELF instrument. It may be that some genes are more influential, in the strength of their effect, in the language domain and others in the overlapping variance shared by reading and language. The findings here suggest that clarification of multi-gene effects can be achieved from focusing on the genes linked to reading as well as the sites associated with language impairments.
The findings here were less clear on the more specific measures of TNS and NWR. Increased sample size will be important in determining if we can differentiate linkages for the more specific measures as suggested by the outcomes of TEGI with chromosome 6 and the correspondence of reading and Omnibus language measures on chromosomes 1 and 15. Yet the sample size of Falcaro et al  was also small and yielded significant linkage for chromosomes 16 (NWR) and 19 (CELF/TNS). It may be that the effects are stronger for chromosomes 16 and 19 than for the loci/genes studied here, which would explain why these loci were missed in the original genome screen.
Differences in outcomes, or power to detect linkages, could also be attributable to differences in phenotype measurement. The measures selected for study in this investigation are standardized test instruments, normed on epidemiologically stratified population-based samples of children external to this study. The TNS and non-word repetition tasks in the previous studies have been internally normed on the sample used for genetics investigation, or normed on selected experimental samples available from investigators’ labs. The import of the differences in measurement instruments is whether the binary variables of affectedness are benchmarked to broader population-based samples of children or to more selected samples. Stronger effects may be apparent in binary classifications based on the low end of the ascertained sample versus the low end of an externally-derived sample. As it now stands, the comparison across studies is confounded by differences in the genes/loci of interest, the instruments used for determination of affectedness, and the methods of analyses. Although it appears that multiple genes contribute in different ways to TNS and NWR, further investigation is needed to sort out the number of genes involved, relative robustness of possible effects across measures, and whether these are separate functions that must both be impaired for severe language impairment .
In sum, this investigation replicated previous reports of linkages of SSD and RD to QTLs on chromosomes 1, 3, 6, 7, and 15. We identified new suggestive linkages to SLI diagnostic phenotypes, as well, and identified new and promising indications of association of SNPs on chromosome 6 to language impairment, SSD and RD. In particular, KIAA0319 appears to play a role in the shared variance in speech, language, and reading phenotypes. The outcomes add to the growing evidence of the likelihood of multiple gene effects on language and related abilities, and the need for studies of participants with concurrent measurements across the domains of interest.
This study was supported by NIDCD DC01803. We wish to thank the following research staff for assistance with genotyping: Judith Kenyon, James Askew, Denise Hoover. Behavioral data management and analyses were carried out by Denise Perpich, Allen Richman, and Hiromi Morikawa. Behavioral data collection was carried out by Jennifer Francois, Amy Kepler, Travis Thompson, Andrea Ash, Karla Barnhill, Amy Chadwell, Pat Cleave, Sean Redmond, Tim Brackenbury, Billie Higheagle, Tracy Hirata-Edds, Stacy Betz, April Matthews, Alyson Abel, Anita Alsop, Michelle Knoll, and Julie Hudson. We thank Ken Wexler for his theoretical insights about possible genetic contributions to grammatical impairments of children with SLI. We especially appreciate the participation of the children and families who contributed time and effort to this longitudinal study.
This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
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