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Objectives: To examine pathological evidence present in a sample of 19th -century settlers to South Australia in the context of an early industrial society., Materials: Skeletal remains of 20 adults and 45 nonadults from the government funded burial site (free ground) of St Mary's Anglican Church Cemetery, gravestones of privately funded burials and local parish records., Methods: Investigation of pathological manifestations of skeletal remains, church records and historic literature. Comparison with similar samples from Britain and from New South Wales., Results: Joint disease seen in 35% of adults. Porosity in bone cortices indicative of vitamin C deficiency seen in 32% of the total sample and porous lesions in the orbit (cribra orbitalia) in 7% of nonadults. Traumatic fractures identified in two adult males. Gastrointestinal conditions were the leading cause of death for nonadults, most adults died of pulmonary conditions. Life expectancy of people buried at the expense of the government was 23.8-42.6 years, those in private burials 57.1 years., Conclusion: Health of migrant settlers from the St Mary's free ground did not differ much from that of a similar population in Britain nor of settlers in New South Wales. Thus, it is characteristic for lower socioeconomic groups in early industrialised societies., Significance: St Mary's sample is a rarity due scarcity of similar Australian skeletal samples., Limitations: Small sample size and lack of similar samples for comparison., Suggestions for Further Research: Comprehensive investigation of dentitions in St Mary's sample and studies of more skeletal samples of early settlers in other Australian locations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Identification of incinerated human remains may rely on genetic analysis of burned bone which can prove far more challenging than fresh tissues. Severe thermal insult results in the destruction or denaturation of DNA in soft tissues, however genetic material may be preserved in the skeletal tissues. Considerations for DNA retrieval from these samples include low levels of exogenous DNA, the dense, mineralised nature of bone, and the presence of contamination, and qPCR inhibitors. This review collates current knowledge in three areas relating to optimising DNA recovery from burned bone: 1) impact of burning on bone and subsequent effects on sample collection, 2) difficulties of preparing burned samples for DNA extraction, and 3) protocols for bone decalcification and DNA extraction. Bone decalcification and various DNA extraction protocols have been tested and optimised for ancient bone, suggesting that prolonged EDTA (Ethylenediaminetetraacetic acid) demineralisation followed by solid-phased silica-based extraction techniques provide the greatest DNA yield. However, there is significantly less literature exploring the optimal protocol for incinerated bones. Although burned bone, like ancient and diagenetic bone, can be considered "low-copy", the taphonomic processes occurring are likely different. As techniques developed for ancient samples are tailored to deal with bone that has been altered in a particular way, it is important to understand if burned bone undergoes similar or different changes. Currently the effects of burning on bone and the DNA within it is not fully understood. Future research should focus on increasing our understanding of the effects of heat on bone and on comparing the outcome of various DNA extraction protocols for these tissues., (Copyright © 2021 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.)

The article examines Genghis Khan's death from the historico-medical perspective. Although several etiologies have been proposed over the years, most of these at a closer look appear to be later inventions by historians. A reassessment of the available evidence suggests instead bubonic plague as the most likely clinical scenario. Genghis Khan's death is also a reflection on the impact of pandemic diseases on leadership in ancient times as well as nowadays., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A deep learning artificial neural network was adapted to the task of sex determination of skeletal remains. The neural network was trained on images of 900 skulls virtually reconstructed from hospital CT scans. When tested on previously unseen images of skulls, the artificial neural network showed 95% accuracy at sex determination. Artificial intelligence methods require no significant expertise to implement once trained, are rapid to use, and have the potential to eliminate human bias from sex estimation of skeletal remains., (Copyright © 2019 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Several studies have associated the earlobe crease sign, discovered by Sanders T. Frank in 1973, with cardiovascular pathology, yet very few studies have focused on the antiquity of this trait, with the most ancient one thought to date back to the Roman Emperor Hadrian (76-138CE). This article presents two more cases from the Italian Renaissance in the works of the artist Andrea Mantegna (1431-1506) and examines them in a multidisciplinary fashion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this paper we analyse the possibility that the early hominin Ardipithecus ramidus had vocal capabilities far exceeding those of any extant non-human primate. We argue that erect posture combined with changes in craniofacial morphology, such as reduced facial and jaw length, not only provide evidence for increased levels of pro-sociality, but also increased vocal ability. Reduced length of the face and jaw, combined with a flexed cranial base, suggests the larynx in this species was situated deeper in the neck than in chimpanzees, a trait which may have facilitated increased vocal ability. We also provide evidence that Ar. ramidus, by virtue of its erect posture, possessed a degree of cervical lordosis significantly greater than chimpanzees. This is indicative of increased mobility of the larynx within the neck and hence increased capacity to modulate vocalisations. In the paleoanthropological literature, these changes in early hominin skull morphology have to date been analysed in terms of a shift in mating and social behaviour, with little consideration given to vocally mediated sociality. Similarly, in the literature on language evolution there is a distinct lacuna regarding links between craniofacial correlates of social and mating systems and vocal ability. These are surprising oversights given that pro-sociality and vocal capability require identical alterations to the common ancestral skull and skeletal configuration. We therefore propose a model which integrates data on whole organism morphogenesis with evidence for a potential early emergence of hominin socio-vocal adaptations. Consequently, we suggest vocal capability may have evolved much earlier than has been traditionally proposed. Instead of emerging in the Homo genus, we suggest the palaeoecological context of late Miocene and early Pliocene forests and woodlands facilitated the evolution of hominin socio-vocal capability. We also propose that paedomorphic morphogenesis of the skull via the process of self-domestication enabled increased levels of pro-social behaviour, as well as increased capacity for socially synchronous vocalisation to evolve at the base of the hominin clade., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background: Doping is a very serious issue bedevilling the sporting arena. It has consequences for athletes' careers, perception of sports in the society and funding of sports events and sporting organisations. There is a widespread perception that doping unfairly improves results of athletes., Methods: A statistical study of information on best lifetime results of top 100 m sprinters (males better than 9.98 s, females 11.00 s), over the period of 1980-2011 was conducted. Athletes were divided into categories of 'doped' (N = 17 males and 14 females), based on self admission, the confirmed detection of known doping agents in their bodies or doping conviction, and 'non-doped' (N = 46 males and 55 females)., Results: No significant differences (unpaired t-test) between dopers and non-dopers were found in their average results: male 'dopers' 9.89 s identical with 'non-dopers' 9.89 s, females 10.84 s and 10.88 s respectively. Slopes of regressions of best results on dates for both 'dopers' and 'non dopers' were not significantly different from zero. This indicates that no general improvement as a group in 100 m sprint results over a quarter of a century occurred irrespective of doping being or not being used., Conclusion: Since there are no statistical differences between athletes found "doping" and the others, one of the following must be true: (1) "doping" as used by athletes so detected does not improve results, or (2) "doping" is widespread and only sometimes detected. Since there was no improvement in overall results during the last quarter of the century, the first conclusion is more likely. Objectively, various "doping" agents have obvious physiological or anatomical effects. These may not translate into better results due to the clandestine use of doping that prevents its scientific structuring. Perception of the effectiveness of doping should be reconsidered. Policy changes may be required to ensure the continued fairness and equity in testing, legislation and sports in general., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Little research has focussed on methods to anatomically sequence ribs. Correct anatomical sequencing of ribs assists in determining the location and distribution of regional trauma, age estimation, number of puncture wounds, number of individuals, and personal identification. The aim of the current study is to develop a method for placing fragmented and incomplete rib sets into correct anatomical position. Ribs 2-10 were used from eleven cadavers of an Australian population. Seven variables were measured from anatomical locations on the rib. General descriptive statistics were calculated for each variable along with an analysis of variance (ANOVA) and ANOVA with Bonferroni statistics. Considerable overlap was observed between ribs for univariate methods. Bivariate and multivariate methods were then applied. Results of the ANOVA with post hoc Bonferroni statistics show that ratios of various dimensions of a single rib could be used to sequence it within adjacent ribs. Using multiple regression formulae, the most accurate estimation of the anatomical rib number occurs when the entire rib is found in isolation. This however, is not always possible. Even when only the head and neck of the rib are preserved, a modified multivariate regression formula assigned 91.95% of ribs into correct anatomical position or as an adjacent rib. Using multivariate methods it is possible to sequence a single human rib with a high level of accuracy and they are superior to univariate methods. Left and right ribs were found to be highly symmetrical. Some rib dimensions were greater in males than in females, but overall the level of sexual dimorphism was low., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Tuberculosis is a re-emerging disease and is a major problem in both developing and developed countries today. An estimated one third of the world's population is infected and almost two million people die from the disease each year. Bone lesions occur in 3-5% of active tuberculosis cases and can be used to diagnose the disease in ancient skeletal remains. A meta-analysis was conducted on 531 palaeopathological tuberculosis cases from 221 sites (7250 BCE to 1899) on all continents for the purpose of testing two hypotheses; (1) the frequency of bone lesions does not change through time and (2) the distribution of lesions throughout the skeleton does not change over time. The frequency of bone lesions was found to significantly decrease over time (P<0.05). The distribution of bone lesions was found to change from mainly spinal in earlier time periods to include more cases in other regions of the skeleton (long bones, joints, hands, feet) in later time periods. This difference in distribution was evaluated using a Chi-squared test and found to be significant (P<0.01). These findings are an important addition to the current knowledge of the evolution of the disease and the Mycobacterium tuberculosis., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Forodesine, a purine nucleoside phosphorylase inhibitor, displays in vitro activity in chronic lymphocytic leukemia (CLL) cells in presence of dGuo, which is the basis for an ongoing clinical trial in patients with fludarabine-refractory CLL. Initial clinical data indicate forodesine has significant activity on circulating CLL cells, but less activity in clearing CLL cells from tissues such as marrow. In tissue microenvironments, lymphocytes interact with accessory stromal cells that provide survival and drug-resistance signals, which may account for residual disease. Therefore, we investigated the impact of marrow stromal cells (MSCs) on forodesine-induced response in CLL lymphocytes. We demonstrate that spontaneous and forodesine-induced apoptosis of CLL cells was significantly inhibited by human and murine MSCs. Forodesine-promoted dGuo triphosphate (dGTP) accumulation and GTP and ATP depletion in CLL cells was inhibited by MSCs, providing a mechanism for resistance. Also, MSCs rescued CLL cells from forodesine-induced RNA- and protein-synthesis inhibition and stabilized and increased Mcl-1 transcript and protein levels. Conversely, MSC viability was not affected by forodesine and dGuo. Collectively, MSC-induced biochemical changes antagonized forodesine-induced CLL cell apoptosis. This provides a biochemical mechanism for MSC-derived resistance to forodesine and emphasizes the need to move toward combinations with agents that interfere with the microenvironment's protective role for improving current therapeutic efforts.

Phosphoinositide 3-kinases (PI3Ks) are among the most frequently activated signaling pathways in cancer. In chronic lymphocytic leukemia (CLL), signals from the microenvironment are critical for expansion of the malignant B cells, and cause constitutive activation of PI3Ks. CXCR4 is a key receptor for CLL cell migration and adhesion to marrow stromal cells (MSCs). Because of the importance of CXCR4 and PI3Ks for CLL-microenvironment cross-talk, we investigated the activity of novel, isoform-selective PI3K inhibitors that target different isoforms of the p110-kDa subunit. Inhibition with p110alpha inhibitors (PIK-90 and PI-103) resulted in a significant reduction of chemotaxis and actin polymerization to CXCL12 and reduced migration beneath MSC (pseudoemperipolesis). Western blot and reverse phase protein array analyses consistently demonstrated that PIK-90 and PI-103 inhibited phosphorylation of Akt and S6, whereas p110delta or p110beta/p110delta inhibitors were less effective. In suspension and MSC cocultures, PI-103 and PIK-90 were potent inducers of CLL cell apoptosis. Moreover, these p110alpha inhibitors enhanced the cytotoxicity of fludarabine and reversed the protective effect of MSC on fludarabine-induced apoptosis. Collectively, our data demonstrate that p110alpha inhibitors antagonize stromal cell-derived migration, survival, and drug-resistance signals and therefore provide a rational to explore the therapeutic activity of these promising agents in CLL.

Hyperostosis frontalis interna is a restricted bilateral thickening of the frontal endocranial surface, which is frequently found in postmenopausal females today. Surprisingly, this condition had a higher male prevalence in its rare archaeological records. This is again highlighted by the oldest known male European hyperostosis frontalis interna case in an adult Celtic from 100 BC presented here. This unique specimen supports earlier suggestions of the possible microevolution of human endocrine regulation, e.g. by sex steroids, and its pathoanatomical impact.

Fossil hominin taxonomy is still debated, chiefly due to the fragmentary nature of fossils and the use of qualitative (subjective) morphological traits. A quantitative analysis of a complete database of hominin cranial capacities (CC, n = 207) and body weight estimates (Wt, n = 285), covering a period from 5.1 ma (millions of years) to 10 ka (thousands of years) shows no discontinuities through time or geographic latitude. Distributions of residuals of CC and Wt around regressions on date and latitude are continuous and do not differ significantly from normal. Thus, with respect to these characteristics, all hominins appear to be a single gradually evolving lineage.

Brain size represented by cranial capacity (CC) is one of the most frequently analysed characters of hominids. Accuracy of individual CC estimates depends on completeness of specimens and methods used for reconstruction and measurement. A file of published estimates of CC of hominids dated from 3.2 Ma (million years) to 10 Ka (thousand years) including 606 estimates for 243 specimens was compiled. In the file, 75 specimens are available with multiple values (3 to 15) obtained by various methods and/or by various authors. Using individuals as classes in ANOVA, intraclass variation, which represents "error" of estimates, was calculated. For the total sample of multiple estimates (N = 382) the error variance is 5315 ml2. The error standard deviation is 73 ml (coefficient of variation (CV = 7.3%), quite large in comparison to the actual variation in CC in modern humans, SD = 157 ml (CV = 11.6%). This large error makes us wonder whether any fossil can be reliably placed with respect to a particular "cerebral Rubicon" between palaeospecies. Recent discussions concerning cranial capacity of Stw505 are a case in point regarding errors in CC estimation. In actual repeated 30 time measurements on a research quality cast we obtained with various methods (water, seeds, plasticine) CC estimates ranging from 484 to 586 ml. The range of estimates in the literature is from 515 to 625 ml. When hominid CC by taxon with date as a covariate is subjected to ANOVA, taxon is responsible for 5% of the variance while date is responsible for the main portion, (89%). The relationship between CC and date is best characterised as a gradual time trend. It is proven by the ANOVA test for linearity, by gamma test for trend and by ASReml fitting of a linear function. The line of best fit to this time trend is a double exponential curve which explains 90% of the total variance in CC: CC = 306.63 (4.83(0.9995)DATE) Essentially the same curve fits subsamples of CC dated at less than 1 Ma and at 3.2-1.0 Ma. This has several implications for the nature of the Darwinian process to be reconstructed.