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.

Age estimation of immature human skeletal remains from mandibular and cranial bone dimensions in the postnatal period.

Age estimation is one of the crucial first steps in the identification of human skeletal remains in both forensic and archeological contexts. In the postnatal period, age is traditionally estimated from dental development or skeletal growth, typically long bone diaphyseal length. However, in many occasions other methods are required. This study provides alternative means of estimating age of juvenile remains from the size of several cranial bones and the mandible. A sample of 185 identified juvenile skeletons between birth and 13 years of age from two European collections were used (Lisbon and Spitalfields). Measurements of the frontal, occipital-lateralis, occipital-basilaris, occipital-squamous, zygomatic, maxilla, and mandible were used to calculate classical calibration regression formulae for the sexes combined. The sample was divided into three age groups birth-2 years, 2-6 years, and 2-12.9 years, depending on bone and its growth trajectory. For all the bones, measurements of the youngest age groups yielded the most precise age estimates. The vault bones on average yielded the best performing models, with the frontal bone having the most precise of all. The mandible performed on par with the best performing cranial bones, particularly in individuals under the age of 2 years. This study provides one of the most comprehensive approaches to juvenile age estimation based on bones of the skull, providing a resource that potentially can help estimate age of juvenile skeletons from a variety of circumstances.

The evolution and changing ecology of the African hominid oral microbiome.

The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.

The morphology of the Late Pleistocene hominin remains from the site of La Cotte de St Brelade, Jersey (Channel Islands).

Thirteen permanent fully erupted teeth were excavated at the Paleolithic site of La Cotte de St Brelade in Jersey in 1910 and 1911. These were all found in the same location, on a ledge behind a hearth in a Mousterian occupation level. They were originally identified as being Neanderthal. A fragment of occipital bone was found in a separate locality in a later season. Recent dating of adjacent sediments gives a probable age of <48 ka. The purpose of this article is to provide an updated description of the morphology of this material and consider its likely taxonomic assignment from comparison with Neanderthal and Homo sapiens samples. One of the original teeth has been lost, and we identify one as nonhominin. At least two adult individuals are represented. Cervix shape and the absence of common Neanderthal traits in several teeth suggest affinities with H. sapiens in both individuals, while crown and root dimensions and root morphology of all the teeth are entirely consistent with a Neanderthal attribution, pointing toward a possible shared Neanderthal and H. sapiens ancestry (the likely date of this material corresponds with the time in which both Neanderthals and H. sapiens were present in Europe). The occipital fragment is stratigraphically more recent and does not exhibit any diagnostic Neanderthal features.

Real-world experience with caplacizumab in the management of acute TTP.

The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving caplacizumab from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial end points and historical outcomes in the precaplacizumab era. Eighty-four of 85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalization (3 days), duration of PEX (7 days), and hospital stay (12 days) were comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalization were favorable compared with historical outcomes (P < .05). Thrombotic thrombocytopenic purpura (TTP) recurred in 5 of 85 patients; all had persistent ADAMTS13 activity < 5 IU/dL. Of 31 adverse events in 26 patients, 17 of 31 (55%) were bleeding episodes, and 5 of 31 (16%) were thrombotic events (2 unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4 of 5 deaths, caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients, including pediatric patients, receiving caplacizumab outside of clinical trials. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

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.

Variation in the timing of enamel formation in modern human deciduous canines.

OBJECTIVES: Deciduous canines are now used increasingly in archaeological and forensic studies to establish the time of birth and as a retrospective source of trace elements incorporated into enamel before and after birth. However, data on the variability of deciduous enamel formation times are scarce. Our objectives were to use daily incremental markings to estimate daily secretion rates, the timing of prenatal, postnatal and total enamel formation and any changes in enamel coverage or prism and stria orientation that occur during enamel formation. MATERIALS AND METHODS: Longitudinal ground sections of 81 deciduous canines were studied with transmitted light microscopy. High-resolution digital images were imported from an Olympus VS-120 virtual slide scanning system into a geographic information system (ArcGIS, ESRI USA) for quantitative and statistical analyses of linear, angular and area measurements of buccal enamel. RESULTS: Daily rates of enamel secretion close to the EDJ were faster than in permanent enamel (3.23 µm/day, SD = 0.54). Prism and stria angles subtended to the EDJ both increased through crown formation. Enamel coverage was low in the cusp and cervix but maximal ∼150 days after birth. The mean prenatal enamel formation time was 118 days (range 60-150, SD, 29.2, n = 24). The overall mean postnatal enamel formation time was 319 days (range 210-420, SD 50.6, n = 67). CONCLUSIONS: Daily enamel secretion rates compared well with previous studies of deciduous enamel, however, enamel extension rates in deciduous cuspal enamel were notably lower. The variability of both prenatal and postnatal deciduous enamel formation times was greater than previously reported.

Bone retouchers and technological continuity in the Middle Stone Age of North Africa.

Evidence for specialised bone tools has recently been reported for the Middle Stone Age of North Africa [one], which complements similar finds of slightly younger age in South Africa [two, three]. However, until now scant reference has been made to lesser known tools also made of bone ('bone retouchers') that were employed specifically as intermediaries for working or refining stone artefacts, that are sometimes present in these assemblages. In this paper we describe 20 bone retouchers from the cave of Grotte des Pigeons at Taforalt in north-east Morocco. This is the largest stratified assemblage of bone retouchers from a North African MSA site, and the biggest single collection so far from the African Continent. A total of 18 bone retouchers was recovered in securely dated archaeological levels spanning a period from ~ 84.5 ka to 24 ka cal BP. A further two bone retouchers were found in a layer at the base of the deposits in association with Aterian artefacts dating to around 85,000 BP and so far represent the earliest evidence of this type of tool at Taforalt. In this paper we present a first, detailed description of the finds and trace the stages of their production, use and discard (chaîne opératoire). At the same time, we assess if there were diachronic changes in their form and function and, finally, explore their presence in relation to stone tools from the same occupation layers of the cave.

Effects of maternal, gestational, and perinatal variables on neonatal line width observed in a modern UK birth cohort.

OBJECTIVES: The objective of this study was to explore potential relationships between neonatal line (NNL) width and early life history variables such as maternal health, gestation, the birth process, and perinatal health. MATERIALS AND METHODS: Histological thin sections of deciduous canines were studied from 71 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). The width of the NNL was measured in three locations on the tooth crown using spatial mapping techniques (ArcGIS) from digital images from an Olympus VS-120 microscope. Life history variables were collected prospectively through a combination of clinical observations and questionnaires. RESULTS: Infants born late term or post term had narrower neonatal lines than those born prematurely or at full term. Infants born in Autumn (September to November) had narrower NNLs than those born at other times of year. NNLs in infants born to mothers with hypertension were wider than those without. Infants resuscitated at birth or born to obese mothers had narrower NNLs than those that were not. There was no association between NNL width and either the type or duration of delivery. DISCUSSION: The NNL in enamel is an irregular accentuated line, but the factors underlying its formation and width remain unclear. In contrast to some previous studies, we found no association between wider NNLs and long or difficult births. Instead, we found that the width of the neonatal line NNL varied in relation to parameters that reflected the prenatal environment and length of gestation.

Sex differences in the patterning of age-related bone loss in the human hallucal metatarsal in rural and urban populations.

OBJECTIVES: Age-degenerative features of the metatarsals are poorly known despite the importance of metatarsal bone properties for investigating mobility patterns. We assessed the role of habitual activity in shaping the patterning and magnitude of sexual dimorphism in age-related bone loss in the hallucal metatarsal. MATERIALS AND METHODS: Cross-sections were extracted at midshaft from micro-computed tomography scan models of individuals from medieval rural (Abingdon Vineyard) and early industrial urban (Spitalfields) settings (n = 71). A suite of cross-sectional geometry dimensions and biomechanical properties were compared between populations. RESULTS: The rural group display generally stronger and larger metatarsals that show a greater capacity to resist torsion and that have comparatively greater bending strength along the medio-lateral plane. Men in both groups show greater values of cortical area than women, but only in the urban group do men show lower magnitudes of age-related decline compared to females. Women in rural and urban populations show different patterns of age-related decline in bone mass, particularly old women in the urban group show a marked decline in cortical area that is absent for women in the rural group. DISCUSSION: Lifetime exposure to hard, physical activity in an agricultural setting has contributed to the attainment of greater bone mass and stronger bones in young adults. Furthermore, over the life-course, less of this greater amount of bone is lost, such that sustained activity levels may have acted to buffer against age-related decline, and this is most pronounced for women, who are expected to experience greater bone loss later in life than men.

Infant funerary behavior and kinship in Pleistocene hunter-gatherers from Morocco.

Infant remains are relatively uncommon in the late Pleistocene (Upper Palaeolithic) archaeological record. Funerary treatment is considered indicative of social status and mirrors cultural attitudes toward the deceased or the group they represent. Here we report on the burials of six infants, including three who died at birth or shortly thereafter, from Later Stone Age (Iberomaurusian) levels at Grotte des Pigeons, Taforalt, in Morocco dating to ∼14,500 cal BP. Funerary treatment of the infants was equivalent to that of older individuals within the community, indicating an inclusive social status. The burials of two of the six infants, shown by previous aDNA analysis to be brother and sister, were overlain by ochre stained grinding stones that may have served as grave markers. In this case, a uniquely shared funerary treatment mirrored a close biological relationship, suggesting that kinship contributed to the patterning of funerary behavior within this Pleistocene burial assemblage.

90,000 year-old specialised bone technology in the Aterian Middle Stone Age of North Africa.

The question of cognitive complexity in early Homo sapiens in North Africa is intimately tied to the emergence of the Aterian culture (~145 ka). One of the diagnostic indicators of cognitive complexity is the presence of specialised bone tools, however significant uncertainty remains over the manufacture and use of these artefacts within the Aterian techno-complex. In this paper we report on a bone artefact from Aterian Middle Stone Age (MSA) deposits in Dar es-Soltan 1 cave on the Atlantic coast of Morocco. It comes from a layer that can be securely dated to ~90 ka. The typological characteristics of this tool, which suggest its manufacture and use as a bone knife, are comparatively similar to other bone artefacts from dated Aterian levels at the nearby site of El Mnasra and significantly different from any other African MSA bone technology. The new find from Dar es-Soltan 1 cave combined with those from El Mnasra suggest the development of a bone technology unique to the Aterian.

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.

Pleistocene North African genomes link Near Eastern and sub-Saharan African human populations.

North Africa is a key region for understanding human history, but the genetic history of its people is largely unknown. We present genomic data from seven 15,000-year-old modern humans, attributed to the Iberomaurusian culture, from Morocco. We find a genetic affinity with early Holocene Near Easterners, best represented by Levantine Natufians, suggesting a pre-agricultural connection between Africa and the Near East. We do not find evidence for gene flow from Paleolithic Europeans to Late Pleistocene North Africans. The Taforalt individuals derive one-third of their ancestry from sub-Saharan Africans, best approximated by a mixture of genetic components preserved in present-day West and East Africans. Thus, we provide direct evidence for genetic interactions between modern humans across Africa and Eurasia in the Pleistocene.

Age estimation of immature human skeletal remains from the dimensions of the girdle bones in the postnatal period.

OBJECTIVES: This study provides classical calibration regression formulae for age estimation from the dimensions of unfused shoulder and pelvic girdle bones. MATERIALS AND METHODS: Age estimation models were derived from a sample of 160 known age and sex individuals (63 females and 97 males) aged birth to 12 years, selected from Portuguese and English skeletal collections. The sample was divided into two age groups at the age of 2 years, and formulae were obtained for the sexes separately and combined. RESULTS: Measurements of the pelvis provide more precise age estimates than the shoulder. In the younger age group, the height and width of the ilium, and the height of the glenoid yield the most precise age estimates. In the older age group, the length of the clavicle provides the most precise estimates, followed by measurements of the pubis and ischium. DISCUSSION: In the younger individuals (<2 years), age estimates based on measurements of the pelvic girdle seem to be as or more precise than those based on the length of long bones. In older individuals (≥2 years), estimates based on the measurements of the girdles are less precise than those based on the length of long bones. These age estimation formulae may be useful for fragmentary and incomplete material in archaeological and forensic contexts. The formulae are suitable for a variety of archeological populations living under adverse conditions. These conditions are similar to some "developing" countries, and hence the formulae may also be applicable to modern forensic remains from such environments.

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.

A comparison of three methods to generate a conceptual understanding of a disease based on the patients' perspective.

BACKGROUND: The Food and Drug Administration patient-reported outcome (PRO) guidance provides standards for PRO development, but these standards bring scientific and logistical challenges which can result in a lengthy and expensive instrument development process. Thus, more pragmatic methods are needed alongside traditional approaches. METHODS: Partnering with the National Ankylosing Spondylitis (AS) Society, we compared three methods for eliciting patient experiences: 1) concept elicitation (CE) interviews with 12 individuals with AS, 2) "group concept mapping" (GCM) with 16 individuals with AS, 3) a social media review (SMR) of AS online chatrooms. Three conceptual models were developed and compared to explore data breadth/depth, as well as the practicalities and patient-centeredness. RESULTS: Overlap in concepts was observed between conceptual models; 35% of symptoms were identified by all methods. The SMR approach identified the most concepts (n = 23), followed by CE interviews (n = 18), and GCM (n = 15). Eight symptoms were uniquely identified using GCM and SMR. Eliciting in-depth data was challenging for SMR as detail was not always provided. Insight into the relationships between symptoms was obtained as a "concept map" in GCM, via effective probing within interviews, and through the subject's descriptions in SMR. Practical investment varied; CE interviews were the most resource intensive, whereas SMR was the least. Individuals in GCM and CE interviews reported high engagement. CONCLUSIONS: Primary CE interviews achieved the greatest depth in conceptual understanding of patient experience; however, novel methods (GCM, SMR) provide complementary approaches for identifying measurement concepts. Each method has strengths and weaknesses and should be selected based on specific research objectives.

Age estimation of immature human skeletal remains from the metaphyseal and epiphyseal widths of the long bones in the post-natal period.

OBJECTIVES: This study provides regression and classical calibration models for the estimation of age from the dimensions of the metaphyses and epiphyses of the six long bones. METHODS: A sample of 148 known sex and age individuals (56 females and 92 males), aged between birth and 12 years of age, selected from Portuguese and English skeletal collections. Age estimation models were obtained separately for each sex and for the sexes combined, for the entire sample and for the sample divided into two subsamples at the age of 2 years. RESULTS: The best performing epiphysis is the proximal epiphysis of the tibia. For the metaphyses, the distal metaphysis of the tibia and the proximal metaphysis of the femur are best for individuals below and above 2 years of age, respectively. Growth of the metaphyses is similar to that of the diaphysis. Results suggest that age can be as accurately estimated from the width of the metaphyses and epiphyses as from the length of the diaphyses, or as from the length of the deciduous and permanent teeth. CONCLUSIONS: These models may be useful for fragmentary material in both archaeological and forensic contexts. However, due to the background of the samples, the models would be most applicable to individuals exposed to adverse environmental conditions during growth and development. Metaphyseal and epiphyseal widths may be less affected by ecological conditions than diaphyseal length.