Acute otitis media (AOM) is one of the most common pediatric conditions worldwide. Peak age of occurrence for AOM has been identified within the first postnatal year and it remains frequent until approximately six postnatal years. Morphological differences between adults and infants in the cartilaginous Eustachian tube (CET) and associated structures may be responsible for development of this disease yet few have investigated normal growth trajectories. We tested hypotheses on coincidence of skeletal growth changes and known ages of peak AOM occurrence. Growth was divided into five dental eruption stages ranging from edentulous neonates (Stage 1) to adults with erupted third maxillary molars (Stage 5). A total of 32 three-dimensional landmarks were used and Generalized Procrustes Analysis was performed. Next, we performed principal components analysis and calculated univariate measures. It was found that growth change in Stage 1 was the most rapid and comprised the largest amount of overall growth in upper respiratory tract proportions (where time is represented by the natural logarithmic transformation of centroid size). The analysis of univariate measures showed that Stage 1 humans did indeed possess the relatively shortest and most horizontally oriented CET's with the greatest amount of growth change occurring at the transition to Stage 2 (eruption of deciduous dentition at five postnatal months, commencing peak AOM incidence) and ceasing by Stage 3 (approximately six postnatal years). Skeletal indicators appear related to peak ages of AOM incidence and may contribute to understanding of a nearly ubiquitous human disease. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1721-1740, 2017. © 2017 Wiley Periodicals, Inc.

There has been considerable study on climatic diversity in human piriform aperture dimensions but relatively little on the posterior nares or choanae. This study quantified shape differences in choanal morphology between two broad groups of “cold” and “tropical” climate human populations. The former consisted of Alaskan Inuits, Aleutian Islanders, Northern Chinese, and Northern Europeans (n=131) while the latter group was comprised of East and West Africans and South East Asians (n=63). Such broad groups were employed to control for any feature not directly related to climate (e.g. facial prognathism). Shape differences were quantified from landmark coordinate data collected via a Microscribe digitizer. After Procrustean superimpositioning, relative distances were compared via Student's t‐tests. The results showed that found that cold climate populations may be distinguished by significantly (p<0.0001) smaller choanal plane angles (more vertically oriented choanae), smaller maximum relative nasopharyngeal depth (staphylion‐sphenobasion chord), and higher relative medial pterygoid plate height. However, none of these features distinguished any single cold climate population from all other tropical populations. Climate likely influences choanal and overall nasopharyngeal morphology in a global context that is discernable only in large‐scale comparison of pooled populations.Grant Funding Source: National Science Foundation

The nasofrontal angle has long been studied within the context of rhinoplasty and aesthetic surgery. However, few have observed the distribution of this trait over clinal zones ranging from temperate to tropical latitudes. This study tests the relationship between climate and nasofrontal angle on a sample (n=130) of dry crania from geographically diverse human populations. The nasofrontal angle was calculated from coordinate data collected among the landmarks glabella, nasion, and rhinion. Specimens of both sexes were used so that the maximum range of variation could be expressed in each population, thus allowing for a more stringent analysis. It was found that northern and southern Europeans are not significantly (p<0.05) different from each other or from North Africans and South East Asians. However, they possessed significantly (p<0.05) smaller (i.e., more acute) angles than the Inuit, Chinese, and East and West African samples, which did not exhibit any significant differences among each other or from the North Africans and South East Asians. Nasofrontal angle may share a closer relationship with nasal projection than climate as leptorrhine Europeans possess the most acute angles. However, the results may indicate separate population histories of Europeans and Inuit who, despite both inhabiting relatively northerly latitudes, developed separate adaptations to cold climate.Grant Funding Source: SUNY Downstate College of Medicine

The internal nares (choanae) lie at the nexus of key respiratory tract functions, yet their comparative and functional morphology in hominoids has been poorly studied. We examined the growth of the choanae and adjacent facial and basicranial regions in crania of extant hominoids ( Homo sapiens , n= 130; Pan troglodytes , n = 32; Gorilla gorilla n= 22; Pongo pygmaeus , n= 17; Symphalangus syndactylus, n= 19; Hylobates hoolock , n= 39) from eruption of the first through third permanent maxillary molars. Shape variation was quantified using 3D landmarks and analyzed with generalized procrustes analysis (GPA). Results show that ontogenetically the relative size and proportions of the choanae remained stable in all observed species. Humans are characterized by shorter, broader choanae than pongids, but not hylobatids, whose choanae are nearly twice as wide as they are tall. Among all hominoids, choanal area is negatively (and significantly; p<.01) correlated with the area of the piriform aperture, flexion at the spheno‐occipital synchondrosis, and facial kyphosis. These results imply a functional relationship between the dimensions of the osseous nasopharynx and overall basicranial flexion. Grant Funding Source n/a

GW572016 (Lapatinib) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor (EGFR, ErbB-1) and ErbB-2. We determined the crystal structure of EGFR bound to GW572016. The compound is bound to an inactive-like conformation of EGFR that is very different from the active-like structure bound by the selective EGFR inhibitor OSI-774 (Tarceva) described previously. Surprisingly, we found that GW572016 has a very slow off-rate from the purified intracellular domains of EGFR and ErbB-2 compared with OSI-774 and another EGFR selective inhibitor, ZD-1839 (Iressa). Treatment of tumor cells with these inhibitors results in down-regulation of receptor tyrosine phosphorylation. We evaluated the duration of the drug effect after washing away free compound and found that the rate of recovery of receptor phosphorylation in the tumor cells reflected the inhibitor off-rate from the purified intracellular domain. The slow off-rate of GW572016 correlates with a prolonged down-regulation of receptor tyrosine phosphorylation in tumor cells. The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures.