Investigating the "scapula sign" as an indicator of rickets.

OBJECTIVE: In 1971, Weiss identified a "scapula sign" comprising a defect at the inferior angle of the scapula in juveniles with vitamin D deficiency rickets, but this has been little studied since. This study aimed to explore pathological variation of this defect in juveniles with other skeletal manifestations of vitamin D deficiency rickets. MATERIALS AND METHODS: 527 juveniles, aged from birth to 12 years, from two post-medieval British assemblages were macroscopically evaluated to document the range of pathological changes at the inferior angle. Scapula maximum lengths were recorded and supplementary radiographs were assessed. RESULTS: Blunting, flattening or squaring of the inferior angle occurred in 34 of 155 (22%) juveniles with other indicators of rickets and occurred frequently in cases of severe active rickets. Coarsening of the border and cupping deformities were identified radiographically, as well as residual defects in healed cases. Scapula lengths in juveniles with active rickets did not consistently deviate from those expected in any age group. CONCLUSIONS: The scapula sign is identifiable in some children with rickets. Differential diagnoses of scapula defects are important but the socio-cultural and environmental context of this sample suggests a link to vitamin D deficiency. SIGNIFICANCE: This finding expands the range of pathological changes known to occur in rickets, helping to improve recognition of this condition in past groups. LIMITATIONS: Small sample sizes prevented observation of the defect in adolescents with rickets. Defects can affect the positioning of standardised scapula length measures, complicating assessments of growth impacts. SUGGESTIONS FOR FUTURE RESEARCH: Continued research into the range of skeletal changes that can develop in vitamin D deficiency to improve the identification of this deficiency in past groups.

Frontal sinuses and human evolution.

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species' holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species.

Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS.

The neuromuscular junction is a synapse critical for muscle strength and coordinated motor function. Unlike CNS injuries, motor neurons mount robust regenerative responses after peripheral nerve injuries. Conversely, motor neurons selectively degenerate in diseases such as amyotrophic lateral sclerosis (ALS). To assess how these insults affect motor neurons in vivo, we performed ribosomal profiling of mouse motor neurons. Motor neuron-specific transcripts were isolated from spinal cords following sciatic nerve crush, a model of acute injury and regeneration, and in the SOD1G93A ALS model. Of the 267 transcripts upregulated after nerve crush, 38% were also upregulated in SOD1G93A motor neurons. However, most upregulated genes in injured and ALS motor neurons were context specific. Some of the most significantly upregulated transcripts in both paradigms were chemokines such as Ccl2 and Ccl7, suggesting an important role for neuroimmune modulation. Collectively these data will aid in defining pro-regenerative and pro-degenerative mechanisms in motor neurons.

Hybridization chain reaction enables a unified approach to multiplexed, quantitative, high-resolution immunohistochemistry and in situ hybridization.

RNA in situ hybridization based on the mechanism of the hybridization chain reaction (HCR) enables multiplexed, quantitative, high-resolution RNA imaging in highly autofluorescent samples, including whole-mount vertebrate embryos, thick brain slices and formalin-fixed paraffin-embedded tissue sections. Here, we extend the benefits of one-step, multiplexed, quantitative, isothermal, enzyme-free HCR signal amplification to immunohistochemistry, enabling accurate and precise protein relative quantitation with subcellular resolution in an anatomical context. Moreover, we provide a unified framework for simultaneous quantitative protein and RNA imaging with one-step HCR signal amplification performed for all target proteins and RNAs simultaneously.

Ontogenetic changes in femoral cross-sectional geometry during childhood locomotor development.

OBJECTIVES: The femur is a major weight-bearing bone that is variably loaded throughout growth as children transition through locomotory states prior to the attainment of a mature bipedal gait. Here, we document ontogenetic trends in femoral cross-sectional geometry (CSG) and explore how changes in loading regime may impact the structural arrangement of cortical bone along the length of the developing diaphysis. MATERIALS AND METHODS: Micro-CT scans of 110 immature femora were generated from a documented archaeological sample ranging in age from birth to 8.5 years old. CSG properties indicative of relative bone strength and bending rigidity were analyzed from cross-sections extracted at 35%, 50% and 65% of total intermetaphyseal length. RESULTS: Infants experience a marked redistribution of cortical bone between birth and 7 months facilitating a more advantageous mechanical structure for early load bearing behaviors as bone is displaced further from the section centroid. Early walkers are characterized by a mediolaterally reinforced cross-section that becomes more circular as gait continues to develop. DISCUSSION: During ontogeny the femur undergoes distinct morphological phases, which correspond with changes in loading regime. This study illustrates the importance of loading conditions in shaping immature bone morphology. Nonmechanical factors such as changes in hormonal environmental can also impact on this dynamic.

Career and professional development services for pharmacy students.

INTRODUCTION: As the number of pharmacy programs and graduates continue to rise, pharmacy students are being faced with new challenges in seeking post-graduate positions. A Career Connections program was established as part of the student affairs office to develop, implement, and evaluate career and professional development at the University of Michigan College of Pharmacy. The objective of this paper was to evaluate student perceptions and value of career and professional development services in preparing students for competitive job and residency markets. METHODS: An electronic survey was administered to second-, third-, and fourth-professional year students and 2017 graduates to evaluate all facets of career and professional development services offered by the college of pharmacy. RESULTS: The majority of students (76.8%) were satisfied with their access to career development services. Of all the services and events evaluated, students were most satisfied with the internship panel, fourth-year residency seminars, and third-year professional development elective course. Additional services recommended by students included more networking opportunities with alumni, continued exposure to different careers in pharmacy, and more emphasis on the job searching process. CONCLUSIONS: Career development services were generally perceived favorably. The college has implemented several changes based on feedback from students, including splitting students into career-based tracks in the professional development elective and adding additional job-searching seminars. Future initiatives will include increasing outreach to college alumni. Career and professional development services at pharmacy programs should be continuously evaluated in a rapidly changing post-graduate landscape.

Perimortem fracture manifestations and mortality after hip fracture in a documented skeletal series.

OBJECTIVE: Unhealed hip fractures are underrepresented in the archaeological record, suggesting that better identification criteria are required. This paper evaluates whether a sample of documented perimortem hip fractures displayed classic perimortem features and which features may facilitate better identification of such fractures in the archaeological record. MATERIALS: Ten individuals from the Robert J. Terry Anatomical Skeletal Collection with documented hip fractures and intervals of survival. METHODS: We observed the skeletal remains macroscopically and with a Keyence VHX-2000 digital microscope at a range of 5x to 100x magnification. RESULTS: 90% of the individuals and 64% of the fragments had identifiable perimortem features; hinging was the most consistent feature. Eburnation was found in two individuals who died 13 days after sustaining a hip fracture. CONCLUSIONS: This study underscores the importance of examining fracture margins for evidence of hinging. Eburnation may be added to the list of potential perimortem fracture identification criteria. SIGNIFICANCE: Identifying perimortem trauma unequivocally remains challenging. Using collections with documented perimortem fractures aids in determining which criteria are most likely to appear in archaeological human bone. LIMITATIONS: The fracture location patterning (70% intertrochanteric) may be the result of sample selection. SUGGESTIONS FOR FUTURE RESEARCH: Further intensive comparative investigation with the Hamann-Todd Collection would elucidate patterns further.

Rare paleopathological insights into vitamin D deficiency rickets, co-occurring illnesses, and documented cause of death in mid-19th century London, UK.

Growing evidence suggests that vitamin D supports immune responses to infections, autoimmune conditions and cancers, although evidence from large-scale studies is limited. There is scope to better understand how vitamin D deficiency interacted with other diseases to affect health in past groups. This study investigated paleopathological evidence and documentary records of individual cause of death to examine disease co-occurrence in a group of mid-19th century child burials from London, UK. Twenty-one percent of children had vitamin D deficiency rickets (138/642) and 36 children with rickets had an identified cause of death. Cyclical episodes of metabolic and nutritional deficiencies (rickets and scurvy) had occurred during childhood. Active rickets co-occurred with respiratory and gastrointestinal infections in a small number of children, likely reflecting vitamin D's role in supporting immune function. Consideration of the stage of the vitamin D deficiency showed that the majority of children were affected by chronic disease loads indicative of multiple episodes of illness. Reconstructions of the wider health consequences of vitamin D deficiency in past groups are dependent on recognising whether the deficiency was active or healed. The variability of diseases identified illustrates the high disease burden that affected children in this socially disadvantaged group.

Endochondral growth disruption during vitamin D deficiency rickets in a mid-19th century series from Bethnal Green, London, UK.

OBJECTIVES: Vitamin D affects many aspects of cartilage and skeletal development. Inconsistent findings currently exist regarding the impact of vitamin D deficiency on childhood growth. This study aims to evaluate the impact of vitamin D deficiency on childhood skeletal development by exploring long bone growth in children with healed and active rickets. MATERIALS AND METHODS: Forty-four known-age children (2 months to 12 years) with rickets and 99 without rickets were compared with modern reference data from North America. Diaphyseal lengths of children with active rickets (34.1%, 15/44), healed rickets (65.9%, 29/44), and without rickets (99/143, 69.2%) were expressed as a percentage of expected length and an average percentage value was calculated across all available long bones. RESULTS: Combined data for all six long bones revealed that children with active rickets had achieved only 75.3% of their expected size whereas, on average, children with healed rickets had achieved 81.6% of their expected size. On average, children without skeletal evidence of rickets had achieved 83.7% of their expected size. Children with severe skeletal manifestations of active rickets had a lower average percentage of expected size (70.4%) than the remainder of children affected by the condition. DISCUSSION: Pronounced growth faltering existed in children with active rickets and affected the upper and lower limb, indicating systemic growth failures during the deficiency. Poor maternal health, early weaning and inadequate infant feeding, and lack of sunlight exposure likely contributed to the development of rickets. Complex interactions between pathological conditions, nutritional deficiencies and vitamin D deficiency may have exacerbated growth impacts.

A Pilot Evaluating Clinical Pharmacy Services in an Ambulatory Psychiatry Setting.

Objectives: A pilot of clinical services provided by psychiatric clinical pharmacists in an outpatient clinic are described and evaluated. The primary objective was to evaluate the difference in change of Patient Health Questionnaire (PHQ)-9 and/or Generalized Anxiety Disorder (GAD) Questionnaire scores between the two groups. Secondary objectives were to assess time patients spent in clinic, time to target psychotropic medication dose, and patient self-reported medication adherence. Experimental Design: Data were collected from January 2014 to November 2015 for patients with depression and/or anxiety who had an appointment within an outpatient psychiatric clinic with either a provider (control) or both a provider and clinical pharmacist (case). Principle Observations: A total of 217 patients were included in the study; 117 patients served as controls and 100 patients received clinical pharmacist intervention. No statistical difference was detected in the primary outcome. However, patients in the case group had higher baseline PHQ-9/GAD scores, and the frequency of measured values was lower than anticipated, limiting power to detect a difference. All secondary outcomes achieved statistical significance. Both time in clinic and time to reach a stabilized psychotropic medication regimen were shorter in the control group. Patient self-reported adherence favored a higher adherence rate in the intervention group. Conclusion: While this study found no significant difference in the change in PHQ-9/GAD scores between groups, it demonstrated the need for enhanced utilization of measurement-based outcomes in the psychiatric setting. Pharmacists provide a range of services to patients and providers and can serve as key partners to enhance measurement-based care.

Patterns of long bone growth in a mid-19th century documented sample of the urban poor from Bethnal Green, London, UK.

OBJECTIVES: Studies of male and female long bone growth in past populations are limited and usually constrained by the lack of personal identification. This article aimed to evaluate long bone growth in a series of mid-19th century documented burials associated with the urban poor from Bethnal Green, London, UK. MATERIALS AND METHODS: Maximum diaphyseal lengths from 74 males and 70 females (2 months to 12 years) were compared to modern reference data from North America. Diaphyseal lengths were expressed as a percentage of expected length and an average percentage value was calculated across all available long bones. An index of growth progression was introduced to explore differences in the progress of males and females towards their projected adult size. RESULTS: Deviation from the expected growth attainment was evident in both sexes in the archaeological series by 2-4 months of age. Only 19.4% (28/144) of the children had attained an average long bone length >90% of the predicted mean in the reference series. The percentage of expected growth attainment decreased steadily in both sexes during infancy and early childhood. Overall, females deviated further from their expected growth progression than males. DISCUSSION: Growth faltering in both males and females was established during infancy (<1 year) with no evidence for recovery in older age groups. Early weaning and inadequate artificial feeding, together with impoverished living conditions and limited sanitary provision, most likely impacted on childhood growth.

Quantification of 3D curvature in the iliac crest: Ontogeny and implications for sex determination in juveniles.

OBJECTIVES: Sex-specific differences in the shape of the iliac crest have been reported based on quantification of simplified curvature using two-dimensional variables or qualitative identification of faint/marked S-shaped curvature. An objective and quantitative approach for the evaluation of iliac crest curvature in juveniles was developed. Using three-dimensional data, ontogenetic variation in iliac curvature was investigated in relation to size and chronological age and its accuracy for sex estimation among juveniles was evaluated. MATERIALS AND METHODS: Three-dimensional geometric morphometric landmarks were collected from virtual models of 53 surface-scanned ilia and used to: (1) quantify differences between male and female shape, and (2) to calculate a measure of sinuosity by extracting linear measurements relative to a plane constructed in virtual space. RESULTS: Males were found to exhibit on average more pronounced curvature of the iliac crest than females in equivalent age groups, and the difference between sexes was more marked on the posterior section of the bone than on the anterior section. Classification accuracy was higher for measurements of sinuosity relative to a three-dimensional plane (62-87%) than for landmarks describing crest shape (64-74%). CONCLUSIONS: An increased likelihood of correct male identification (reduced rate of false positive identification) was observed in older children (>5 years). This reflects divergence of male and female iliac crest shape with size (or age), and the development of a unique, more curved iliac crest shape in males. The results suggest more conspicuous male trait expression than female trait expression.

Shape, size, and maturity trajectories of the human ilium.

Morphological traits of the ilium have consistently been more successful for juvenile sex determination than have techniques applied to other skeletal elements, however relatively little is known about the ontogeny and maturation of size and shape dimorphism in the ilium. We use a geometric morphometric approach to quantitatively separate the ontogeny of size and shape of the ilium, and analyze interpopulation differences in the onset, rate and patterning of sexual dimorphism. We captured the shape of three traits for a total of 191 ilia from Lisbon (Portugal) and London (UK) samples of known age and sex (0-17 years). Our results indicate that a) there is a clear dissociation between the ontogeny of size and shape in males and females, b) the ontogeny of size and shape are each defined by non-linear trajectories that differ between the sexes, c) there are interpopulation differences in ontogenetic shape trajectories, which point to population-specific patterning in the attainment of sexual dimorphism, and d) the rate of shape maturation and size maturation is typically higher for females than males. Male and female shape differences in the ilium are brought about by trajectory divergence. Differences in size and shape maturation between the sexes suggest that maturity may confound our ability to discriminate between the sexes by introducing variation not accounted for in age-based groupings. The accuracy of sex determination methods using the ilium may be improved by the use of different traits for particular age groups, to capture the ontogenetic development of shape in both sexes.

An unusual double supernumerary maxillary mesiodens in a Middle Iron Age skeleton from South Uist, Western Isles, Scotland.

OBJECTIVE: Bilaterally occurring and fully erupted mesiodens occur infrequently in the modern population and have been little documented from past populations. This research presents an unusual case of a double maxillary mesiodens in the permanent dentition occurring in skeletal remains dating to the Middle Iron Age (250-410 AD) from South Uist, Western Isles of Scotland. METHODS: Osteological analysis of an adult male included the inventory of teeth present/absent and analysis of dental pathologies (caries, calculus, periodontal disease, ante-mortem tooth loss, periapical abscesses), developmental defects and orthodontic anomalies (enamel hypoplastic defects, malposition, rotation, crowding, agenesis and supernumerary teeth). RESULTS: An unusual expression of double, fully erupted, mesiodens in the anterior permanent maxillary dentition representing supernumerary central incisors exists. The complete eruption had contributed to anterior displacement of one central incisor alveolar socket similar to documented modern clinical cases. Shallow sockets also implied an associated stunted development of the original central maxillary incisor roots. Occlusal enamel wear indicated the mesiodens had been abraded during mastication. CONCLUSION: Current clinical data suggest there is a much higher tendency for single mesiodens to exist rather than double and examples often fail to fully erupt into the dentition. This relative rarity may account for the few previous reports of this dental anomaly from past human remains and especially of this date. The fully erupted double example from South Uist contributes to the known evidence for orthodontic anomalies in the past.

New findings in the identification of adult vitamin D deficiency osteomalacia: Results from a large-scale study.

This is the first systematic large-scale palaeopathological study of adult vitamin D deficiency osteomalacia. One thousand one hundred and eighty-one skeletons from multiple urban contexts in post-mediaeval England (c. AD 1700-1855) were analysed. Twelve adults with evidence of osteomalacia were identified. When added to the seven cases previously identified by Brickley et al. (2007) the individual prevalence rate increased to 19 of 1323 individuals (1.43%). New lesions affecting the medial ilium, scapula coracoid process, proximal femur and vertebrae are presented. These are infrequently occurring indicators, but are important in expanding the previously documented range of skeletal changes of adult osteomalacia and may aid the future identification of this condition in archaeological human remains. Importantly, the pathological lesions recorded in archaeological skeletons were different in expression to those observed in pathology museum collections. The more extreme changes found in many museum collections were not identified in this study. A trend for osteomalacia to have occurred in older adults is demonstrated in these results, raising questions over the impacts on health at different stages of the life course.

The effects of socioeconomic status on endochondral and appositional bone growth, and acquisition of cortical bone in children from 19th century Birmingham, England.

Endochondral growth, appositional growth, and acquisition of cortical bone thickness in the femur are investigated in subadult skeletons (N = 43, dental age range birth to 12 years) from the 19(th)-century AD burial site of St. Martin's churchyard, Birmingham, England. Endochondral growth is monitored using diaphyseal femoral length. Appositional growth is monitored using radiographic midshaft mediolateral width and acquisition of cortical bone using combined mediolateral cortical thickness measured at the midshaft from radiographs. The methodology involves plotting these variables against dental age. Growth is compared in children of differing socioeconomic status. Higher and lower status individuals are identified in the assemblage by their burial in brick vaults in the case of the former and in earth-cut graves in the case of the latter. The relationships between bone dimensions and dental age are described using a polynomial regression procedure, and analysis of regression residuals is used to evaluate differences in bone dimension-for-dental age between the two status groups. Results show that lower socioeconomic status individuals had lower cortical thickness-for-dental age than those of higher status. This was interpreted as likely reflecting poorer nutrition in the children of lower socioeconomic backgrounds. There was no patterning with respect to socioeconomic status in femur diaphyseal length or midshaft width. The results support the idea that, for skeletal populations, growth in cortical thickness may be a more sensitive indicator of adverse conditions in childhood than growth in bone length or width.

An investigation of skeletal indicators of vitamin D deficiency in adults: effective markers for interpreting past living conditions and pollution levels in 18th and 19th century Birmingham, England.

Vitamin D deficiency in adults is referred to as osteomalacia, and this condition has multiple causes related to factors such as environment, living conditions and cultural practices. Therefore, understanding the types and range of expression of osteomalacia in archaeological bone, using a number of investigative techniques, will have significant implications for interpretations made about past communities. This study aimed to understand the expression of vitamin D deficiency in the skeletons of adults through detailed analysis of human bone from the late 18(th) and 19(th) century churchyard of St. Martin's, Birmingham, England, at a gross, radiological and histological level. The collection from St. Martin's is unusual for the period as this central burial ground in Birmingham was used by a wide cross section of society rather than a narrow socio-economic group as at other sites of this date. Macroscopic and radiological analysis of 291 adults identified seven individuals with osteomalacia, and histological analysis using back-scattered scanning electron microscopy confirmed the findings. Detailed description of the range of pathological alterations observed in the archaeological skeletons are presented, and possible interpretations of the patterns seen considered. The results of this investigation will enable clear diagnosis and interpretation of this vitamin D deficiency disease, an important socio-economic indicator, to take place in the future.

Skeletal manifestations of infantile scurvy.

Recent investigations of human skeletal material from the historic St. Martin's cemetery, England, found a range of abnormal lesions in six infants that are almost certainly related to scurvy. Porous and proliferative bone lesions affecting the cranial bones and scapulae were found, and this paper presents images obtained using both macroscopic and scanning electron microscope examination of the lesions. Previous work on infantile scurvy (Ortner et al., 1997-2001) relied heavily on changes at the sphenoid, which is often missing in archaeological bone, so the identification of changes attributable to scurvy on other cranial bones and the scapulae is encouraging. The ability to recognize changes related to scurvy on a range of bones will ensure an enhanced potential for recognition of this disease in future research involving archaeological bone. Research on historical documents from Birmingham dating to the eighteenth and nineteenth centuries, combined with the probable cases of scurvy identified, supports the view that the paucity of cases of infantile scurvy from the archaeological record reflects a lack of understanding and recognition of bone manifestations, rather than a lack of occurrence in this period. Changes linked to scurvy were only found in infants from the poorer sections of the community from St. Martin's, and this is almost certainly linked to patterns of food consumption and may be related to shortages of potatoes, due to blight, experienced during this period.