Publications

2025

Blumer, Janice, Irisa Arney, Anna M. Hardin, Morgan Nichols, Luke Arsenault, and John Petrucci. 2025. “Comparing Cranial Suture Interdigitation in Humans and Non-Human Primates: Unearthing Links to Osteopathic Cranial Concept”. Journal of Osteopathic Medicine 125 (2): 87-94.

Context: Since William Garner Sutherland’s inception of osteopathic cranial manipulative medicine (OCMM), osteopathic physicians have practiced with the knowledge that cranial sutures exhibit motion. We hypothesize that the complexity of suture interdigitation in humans may provide clues to elucidate the concept of OCMM.

Objectives: We compared the interdigitation of sagittal, coronal (left and right), and lambdoid (left and right) sutures in computed tomography (CT) scans of humans and five nonhuman primate species (Gorilla gorilla, Pongo pygmaeus, Pan troglodytes, Hylobates lar, and Nasalis larvatus).

Methods: Human ages are evenly distributed between 10 and 65 years of age, with an equal number of males (n=16) and females (n=16) in the sample. Nonhuman primates are all females, and the sample includes juveniles (n=6) and adults (n=34). Sutures were evaluated on a scale ranging from 0 to 3 (0: fused sutures; 1: no interdigitation; 2: low complexity; and 3: representing the highest degree of interdigitation and complexity).

Results: Based on ordinary least squares linear regression, we found no significant relationship between suture interdigitation and age in humans. Chi-square tests were utilized to assess sex differences within humans, species-level differences, and differences between humans and nonhuman primates across all five sutures. Humans exhibited a statistically significant greater degree of suture complexity than all five nonhuman species across all five sutures.

Conclusions: These findings indicate that human suture interdigitation is more complex than their closest living relatives (African apes) and other primates (Asian monkeys and apes). We theorize that this would enable subtle movement and serve to transmit forces at the cranial sutures from dietary or ethological behaviors, similar to the pattern observed in other mammals. While humans have a softer diet compared to other living primates, the uniqueness of human craniofacial growth and extended developmental period could contribute to the necessity for complex cranial sutures. More studies are needed to understand variation in human and nonhuman sutural complexity and its relationship to cranial motion.

Schwartz, Jay W., Natasha E. Polly, Abby K. Deshon, Veda A. Duffy, Rachel Munoz, and Anna M. Hardin. 2025. “Acoustic Classification and Human Perception of Domestic Cat Vocalizations”. Animal Behaviour 224.

An important step in the study of animal vocal communication is to elucidate the species' vocal repertoire: the set of call types produced by that species, each with biologically distinct production mechanisms, functions and meaning. The goal of the present study was to characterize the vocal repertoire of domestic cats, Felis catus, while investigating function and meaning through human perception. In Study 1, we subjected a sample of 212 cat vocalizations to an unsupervised fuzzy clustering algorithm based on 10 acoustic parameters to identify acoustically distinct call categories. In Study 2, 237 human listeners classified 50 cat vocalizations into one of seven call type categories such as ‘chirp’, ‘meow’ and ‘yowl’ and rated their perceptions of the vocalizers' emotional arousal (intensity of emotion) and valence (positivity or negativity of emotion). The clustering solution identified four call categories with distinct acoustic identities but substantial gradation, corresponding roughly to listener classification as tonal meows, chirps, noisy meows and shrieks/trills. Listeners provided significantly different classifications and emotion ratings to sounds based on cluster membership. While listeners classified some calls based on consistent acoustic features (e.g. chirps), others were less consistent (e.g. yowls), suggesting folk call categories do not necessarily reflect distinct acoustic classes or biological call types. Emotion ratings were correlated with call duration and interactions between duration, noisiness and mean fundamental frequency. Together these results demonstrate the significance of acoustic variation between and within call types in human perception of heterospecific vocalizations, supporting a model in which listeners base emotion attribution in part on the call type. The present study illustrates the promise of unsupervised clustering for minimizing bias and promoting understanding of cat vocal communication.

Lane, Fiona, Alexander Jonson, Kevin Hare, Megan Forgie, Michelle Riedel, and Anna M. Hardin. 2025. “Cadaveric Case Report of Pelvic and Abdominal Anatomy in an Individual With a Müllerian Duct Anomaly”. Cureus 18 (3).

Müllerian duct anomalies (MDAs) are a congenital abnormality of the paramesonephric ducts that result in malformation of the uterus, cervix, and/or vagina. Here, the authors present a class I MDA potentially suggesting Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with two masses incidentally found upon dissection into the uterine cavity. Only a single MRKH syndrome with uterine masses in cadavers has been previously described in the literature. The authors aim to enrich the body of gynecological and reproductive research currently available by increasing understanding of the types of MDAs and to increase anatomical understanding of the condition. This will help anatomists and students of anatomy identify MDAs during dissection, which will ultimately help physicians more appropriately counsel future patients in reproductive health and direct them to appropriate treatment.

Yamaguchi, Craig T L, Conor Davenport, Andres Harris Caceres, Andrew Lataille, Idrees Mohammed Mirani, Josh Cook, Alastair E Moody, and Anna M Hardin. 2025. “Ultrasound-Guided Arterial and Venous Catheterization Training Utilizing Cadaveric Models.”. A&A Practice 19 (3): e01943. https://doi.org/10.1213/XAA.0000000000001943.

Medical students often have limited exposure to advanced ultrasound-guided vascular access techniques within their preclinical curriculum. We evaluated the changes in confidence scores among 15 preclinical medical students before and after undertaking a novel ultrasound-guided cadaver-based training program for vascular access. Pre- and posttraining surveys showed significant confidence increases (P < .05) in understanding vascular anatomy, using ultrasound clinically, and performing femoral, radial, and internal jugular catheterizations. Cadaver-based training is an accessible and promising avenue to teach complex procedural skills in preclinical medical education.

Hardin, Anna M. 2025. “Genetic Correlations Among Dental, Mandibular, and Postcranial Dimensions in Rhesus Macaques (Macaca Mulatta).”. American Journal of Biological Anthropology 186 (1): e25059. https://doi.org/10.1002/ajpa.25059.

OBJECTIVES: Tooth dimensions typically scale with mandibular and postcranial size in primates, although the exact pattern of scaling varies. This study assesses whether correlations by tissue type, anatomical region, or function (mastication or intrasexual competition) are present and could therefore act as evolutionary constraints on tooth-jaw-body size relationships by estimating genetic and phenotypic correlations between dental, mandibular, and postcranial dimensions in rhesus macaques (Macaca mulatta).

MATERIALS AND METHODS: The teeth, mandibles, and postcrania of 362 adults from the Cayo Santiago skeletal collection were measured. Humeral and femoral articular surfaces were selected to represent skeletal elements frequently used to reconstruct primate body size. Genetic correlations were estimated in SOLAR. Random skewers analyses were used to compare genetic and phenotypic correlation matrices to each other and to test matrices.

RESULTS: The genetic correlation matrix was most similar to the test matrix of integration by tissue type (tooth and bone) (r = 0.765, p < 0.001), and nearly as similar to the anatomical region test matrix (r = 0.714, p < 0.001). Hierarchical clustering of the genetic correlation matrix showed similar separation by tissue type. Phenotypic correlation matrices were significantly similar to the genetic correlation matrix (r = 0.813-0.846, p < 0.001) and to most of the test matrices.

CONCLUSIONS: Postcanine dental traits were highly heritable but were not closely genetically correlated with mandibular or postcranial dimensions. These findings indicate that scaling relationships between tooth and bone may be maintained in some populations through nongenetic, environmental factors rather than genetic constraints.

2022

Hardin, Anna M, Ryan P Knigge, Hee Soo Oh, Manish Valiathan, Dana L Duren, Kieran P McNulty, Kevin M Middleton, and Richard J Sherwood. 2022. “Estimating Craniofacial Growth Cessation: Comparison of Asymptote- and Rate-Based Methods”. The Cleft Palate-Craniofacial Journal. 59 (2): 230-38. https://doi.org/10.1177/10556656211002675.

OBJECTIVE: To identify differences between asymptote- and rate-based methods for estimating age and size at growth cessation in linear craniofacial measurements.

DESIGN: This is a retrospective, longitudinal study. Five linear measurements were collected from lateral cephalograms as part of the Craniofacial Growth Consortium Study (CGCS). Four estimates of growth cessation, including 2 asymptote- (GCasym, GCerr) and 2 rate-based (GCabs, GC10%) methods, from double logistic models of craniofacial growth were compared.

PARTICIPANTS: Cephalometric data from participants in 6 historic longitudinal growth studies were included in the CGCS. At least 1749 individuals (870 females, 879 males), unaffected by craniofacial anomalies, were included in all analyses. Individuals were represented by a median of 11 images between 2.5 and 31.3 years of age.

RESULTS: GCasym consistently occurred before GCerr and GCabs consistently occurred before GC10% within the rate-based approaches. The ordering of the asymptote-based methods compared to the rate-based methods was not consistent across measurements or between males and females. Across the 5 measurements, age at growth cessation ranged from 13.56 (females, nasion-basion, GCasym) to 24.39 (males, sella-gonion, GCerr).

CONCLUSIONS: Adolescent growth cessation is an important milestone for treatment planning. Based on our findings, we recommend careful consideration of specific definitions of growth cessation in both clinical and research settings since the most appropriate estimation method may differ according to patients' needs. The different methods presented here provide useful estimates of growth cessation that can be applied to raw data and to a variety of statistical models of craniofacial growth.

Hardin, Anna M, Ryan P Knigge, Dana L Duren, Sarah Williams-Blangero, Janardan Subedi, Michael C Mahaney, and Richard J Sherwood. 2022. “Genetic Influences on Dentognathic Morphology in the Jirel Population of Nepal”. Anatomical Record. 305 (9): 2137-57. https://doi.org/10.1002/ar.24857.

Patterns of genetic variation and covariation impact the evolution of the craniofacial complex and contribute to clinically significant malocclusions in modern human populations. Previous quantitative genetic studies have estimated the heritabilities and genetic correlations of skeletal and dental traits in humans and nonhuman primates, but none have estimated these quantitative genetic parameters across the dentognathic complex. A large and powerful pedigree from the Jirel population of Nepal was leveraged to estimate heritabilities and genetic correlations in 62 maxillary and mandibular arch dimensions, incisor and canine lengths, and post-canine tooth crown areas (N ≥ 739). Quantitative genetic parameter estimation was performed using maximum likelihood-based variance decomposition. Residual heritability estimates were significant for all traits, ranging from 0.269 to 0.898. Genetic correlations were positive for all trait pairs. Principal components analyses of the phenotypic and genetic correlation matrices indicate an overall size effect across all measurements on the first principal component. Additional principal components demonstrate positive relationships between post-canine tooth crown areas and arch lengths and negative relationships between post-canine tooth crown areas and arch widths, and between arch lengths and arch widths. Based on these findings, morphological variation in the human dentognathic complex may be constrained by genetic relationships between dental dimensions and arch lengths, with weaker genetic correlations between these traits and arch widths allowing for variation in arch shape. The patterns identified are expected to have impacted the evolution of the dentognathic complex and its genetic architecture as well as the prevalence of dental crowding in modern human populations.

Knigge, Ryan P, Anna M Hardin, Kevin M Middleton, Kieran P McNulty, Hee Soo Oh, Manish Valiathan, Dana L Duren, and Richard J Sherwood. 2022. “Craniofacial Growth and Morphology Among Intersecting Clinical Categories”. Anatomical Record. 305 (9): 2175-2206. https://doi.org/10.1002/ar.24870.

Differential patterns of craniofacial growth are important sources of variation that can result in skeletal malocclusion. Understanding the timing of growth milestones and morphological change associated with adult skeletal malocclusions is critical for developing individualized orthodontic growth modification strategies. To identify patterns in the timing and geometry of growth, we used Bayesian modeling of cephalometrics and geometric morphometric analyses with a dense, longitudinal sample consisting of 15,407 cephalograms from 1,913 individuals between 2 and 31 years of age. Individuals were classified into vertical facial types (hyper-, normo-, hypo-divergent) and anteroposterior (A-P) skeletal classes (Class I, Class II, Class III) based on adult mandibular plane angle and ANB angle, respectively. These classifications yielded eight facial type-skeletal class categories with sufficient sample sizes to be included in the study. Four linear cephalometrics representing facial heights and maxillary and mandibular lengths were fit to standard double logistic models generating type-class category-specific estimates for age, size, and rate of growth at growth milestones. Mean landmark configurations were compared among type-class categories at four time points between 6 and 20 years of age. Overall, morphology and growth patterns were more similar within vertical facial types than within A-P classes and variation among A-P classes typically nested within variation among vertical types. Further, type-class-associated variation in the rate and magnitude of growth in specific regions identified here may serve as targets for clinical treatment of complex vertical and A-P skeletal malocclusion and provide a clearer picture of the development of variation in craniofacial form.

2021

Knigge, Ryan P, Kieran P McNulty, Heesoo Oh, Anna M Hardin, Emily Leary V, Dana L Duren, Manish Valiathan, and Richard J Sherwood. 2021. “Geometric Morphometric Analysis of Growth Patterns Among Facial Types”. American Journal of Orthodontics and Dentofacial Orthopedics. 160 (3): 430-41. https://doi.org/10.1016/j.ajodo.2020.04.038.

INTRODUCTION: Extreme patterns of vertical facial divergence are of great importance to clinicians because of their association with dental malocclusion and functional problems of the orofacial complex. Understanding the growth patterns associated with vertical facial divergence is critical for clinicians to provide optimal treatment. This study evaluates and compares growth patterns from childhood to adulthood among 3 classifications of vertical facial divergence using longitudinal, lateral cephalograms from the Craniofacial Growth Consortium Study.

METHODS: Participants (183 females, 188 males) were classified into 1 of 3 facial types on the basis of their adult mandibular plane angle (MPA): hyperdivergent (MPA >39°; n = 40), normodivergent (28° ≤ MPA ≤ 39°; n = 216), and hypodivergent (MPA <28°; n = 115). Each individual had 5 cephalograms between ages 6 and 20 years. A set of 36 cephalometric landmarks were digitized on each cephalogram. Landmark configurations were superimposed to align 5 homologous landmarks of the anterior cranial base and scaled to unit centroid size. Growth trajectories were calculated using multivariate regression for each facial type and sex combination.

RESULTS: Divergent growth trajectories were identified among facial types, finding more similarities in normodivergent and hypodivergent growth patterns than either share with the hyperdivergent group. Through the use of geometric morphometric methods, new patterns of facial growth related to vertical facial divergence were identified. Hyperdivergent growth exhibits a downward rotation of the maxillomandibular complex relative to the anterior cranial base, in addition to the increased relative growth of the lower anterior face. Conversely, normodivergent and hypodivergent groups exhibit stable positioning of the maxilla relative to the anterior cranial base, with the forward rotation of the mandible. Furthermore, the hyperdivergent maxilla and mandible become relatively shorter and posteriorly positioned with age compared with the other groups.

CONCLUSIONS: This study demonstrates how hyperdivergent growth, particularly restricted growth and positioning of the maxilla, results in a higher potential risk for Class II malocclusion. Future work will investigate growth patterns within each classification of facial divergence.

Sherwood, Richard J, Hee Soo Oh, Manish Valiathan, Kieran P McNulty, Dana L Duren, Ryan P Knigge, Anna M Hardin, Christina L Holzhauser, and Kevin M Middleton. 2021. “Bayesian Approach to Longitudinal Craniofacial Growth: The Craniofacial Growth Consortium Study”. Anatomical Record. 304 (5): 991-1019. https://doi.org/10.1002/ar.24520.

Early in the 20th century, a series of studies were initiated across North America to investigate and characterize childhood growth. The Craniofacial Growth Consortium Study (CGCS) combines craniofacial records from six of those growth studies (15,407 lateral cephalograms from 1,913 individuals; 956 females, 957 males, primarily European descent). Standard cephalometric points collected from the six studies in the CGCS allows direct comparison of craniofacial growth patterns across six North American locations. Three assessors collected all cephalometric points and the coordinates were averaged for each point. Twelve measures were calculated from the averaged coordinates. We implemented a multilevel double logistic equation to estimate growth trajectories fitting each trait separately by sex. Using Bayesian inference, we fit three models for each trait with different random effects structures to compare differences in growth patterns among studies. The models successfully identified important growth milestones (e.g., age at peak growth velocity, age at cessation of growth) for most traits. In a small number of cases, these milestones could not be determined due to truncated age ranges for some studies and slow, steady growth in some measurements. Results demonstrate great similarity among the six growth studies regarding craniofacial growth milestone estimates and the overall shape of the growth curve. These similarities suggest minor variation among studies resulting from differences in protocol, sample, or possible geographic variation. The analyses presented support combining the studies into the CGCS without substantial concerns of bias. The CGCS, therefore, provides an unparalleled opportunity to examine craniofacial growth from childhood into adulthood.