William Berthon

Female burials equipped with weapons, a topic of interest among scholars and the general public, remain rare occurrences in archaeological records. The interpretation of such cases requires an interdisciplinary approach and a comprehensive evaluation of the available evidence, particularly regarding the sex and potential lifestyle of the deceased. Consequently, data on specific populations, regions, and time periods remain scarce. For instance, no such case has been reported before concerning the 10^th century CE of the Carpathian Basin, known as the Hungarian Conquest period. Our study focuses on an interdisciplinary investigation of a previously known burial, grave No. 63 from the 10^th-century-CE cemetery of Sárrétudvari–Hízóföld (eastern Hungary), which represents a unique case with grave goods including jewelry typically associated with females and archery equipment traditionally linked to males. Through archeological, anthropological, and archaeogenetic analyses, we aim to determine if this case represents the first-known female burial with weapon from the 10^th-century-CE Carpathian Basin. Despite the poor bone preservation, a factor limiting data recording and evaluation, all analyses consistently indicate that the skeletal remains belonged to a female individual. The burial customs, including weapon equipment composition show analogies with male counterparts in the series. In addition, the pattern of pathological and supposed activity-related changes observed on the bones may have resulted from regular physical activity during her lifetime. In summary, our findings support the identification of this case as the first known female burial with weapon from the 10^th-century-CE Carpathian Basin.

Aims/hypothesis: Whether hypoglycaemia increases the risk of other adverse outcomes in diabetes remains controversial, especially for hypoglycaemia episodes not requiring assistance from another person. An objective of the Hypoglycaemia REdefining SOLutions for better liVEs (Hypo-RESOLVE) project was to create and use a dataset of pooled clinical trials in people with type 1 or type 2 diabetes to examine the association of exposure to all hypoglycaemia episodes across the range of severity with incident event outcomes: death, CVD, neuropathy, kidney disease, retinal disorders and depression. We also examined the change in continuous outcomes that occurred following a hypoglycaemia episode: change in eGFR, HbA_1c, blood glucose, blood glucose variability and weight. Methods: Data from 84 trials with 39,373 participants were pooled. For event outcomes, time-updated Cox regression models adjusted for age, sex, diabetes duration and HbA_1c were fitted to assess association between: (1) outcome and cumulative exposure to hypoglycaemia episodes; and (2) outcomes where an acute effect might be expected (i.e. death, acute CVD, retinal disorders) and any hypoglycaemia exposure within the last 10 days. Exposures to any hypoglycaemia episode and to episodes of given severity (levels 1, 2 and 3) were examined. Further adjustment was then made for a wider set of potential confounders. The within-person change in continuous outcomes was also summarised (median of 40.4 weeks for type 1 diabetes and 26 weeks for type 2 diabetes). Analyses were conducted separately by type of diabetes. Results: The maximally adjusted association analysis for type 1 diabetes found that cumulative exposure to hypoglycaemia episodes of any level was associated with higher risks of neuropathy, kidney disease, retinal disorders and depression, with risk ratios ranging from 1.55 (p=0.002) to 2.81 (p=0.002). Associations of a similar direction were found when level 1 episodes were examined separately but were significant for depression only. For type 2 diabetes cumulative exposure to hypoglycaemia episodes of any level was associated with higher risks of death, acute CVD, kidney disease, retinal disorders and depression, with risk ratios ranging from 2.35 (ppp=0.017) to 2.68 (p<0.0001). These associations varied in magnitude and significance when examined separately by hypoglycaemia level. Within the range of hypoglycaemia defined by levels 1, 2 and 3, we could not find any evidence of a threshold at which risk of these consequences suddenly became pronounced. Conclusions/interpretation: These data are consistent with hypoglycaemia being associated with an increased risk of adverse events across several body systems in diabetes. These associations are not confined to severe hypoglycaemia requiring assistance. Graphical

Aims/hypothesis: The objective of the Hypoglycaemia REdefining SOLutions for better liVES (Hypo-RESOLVE) project is to use a dataset of pooled clinical trials across pharmaceutical and device companies in people with type 1 or type 2 diabetes to examine factors associated with incident hypoglycaemia events and to quantify the prediction of these events. Methods: Data from 90 trials with 46,254 participants were pooled. Analyses were done for type 1 and type 2 diabetes separately. Poisson mixed models, adjusted for age, sex, diabetes duration and trial identifier were fitted to assess the association of clinical variables with hypoglycaemia event counts. Tree-based gradient-boosting algorithms (XGBoost) were fitted using training data and their predictive performance in terms of area under the receiver operating characteristic curve (AUC) evaluated on test data. Baseline models including age, sex and diabetes duration were compared with models that further included a score of hypoglycaemia in the first 6 weeks from study entry, and full models that included further clinical variables. The relative predictive importance of each covariate was assessed using XGBoost’s importance procedure. Prediction across the entire trial duration for each trial (mean of 34.8 weeks for type 1 diabetes and 25.3 weeks for type 2 diabetes) was assessed. Results: For both type 1 and type 2 diabetes, variables associated with more frequent hypoglycaemia included female sex, white ethnicity, longer diabetes duration, treatment with human as opposed to analogue-only insulin, higher glucose variability, higher score for hypoglycaemia across the 6 week baseline period, lower BP, lower lipid levels and treatment with psychoactive drugs. Prediction of any hypoglycaemia event of any severity was greater than prediction of hypoglycaemia requiring assistance (level 3 hypoglycaemia), for which events were sparser. For prediction of level 1 or worse hypoglycaemia during the whole follow-up period, the AUC was 0.835 (95% CI 0.826, 0.844) in type 1 diabetes and 0.840 (95% CI 0.831, 0.848) in type 2 diabetes. For level 3 hypoglycaemia, the AUC was lower at 0.689 (95% CI 0.667, 0.712) for type 1 diabetes and 0.705 (95% CI 0.662, 0.748) for type 2 diabetes. Compared with the baseline models, almost all the improvement in prediction could be captured by the individual’s hypoglycaemia history, glucose variability and blood glucose over a 6 week baseline period. Conclusions/interpretation: Although hypoglycaemia rates show large variation according to sociodemographic and clinical characteristics and treatment history, looking at a 6 week period of hypoglycaemia events and glucose measurements predicts future hypoglycaemia risk. Graphical

William Berthon, Stuart J. McGurnaghan, Luke A.K. Blackbourn, Louise E. Bath, David A. McAllister, Diane Stockton, Sarah H. Wild, Paul M. McKeigue, Helen M. Col

Recently, the combined macroscopic and statistical evaluation of 427 identified pre‐antibiotic era skeletons from the Terry Collection (Washington, DC, USA) revealed that there is a positive association between tuberculous meningitis (TBM) and four endocranial alteration types, namely, granular impressions (GIs), abnormal blood vessel impressions (ABVIs), periosteal appositions (PAs), and abnormally pronounced digital impressions (APDIs). Although all the four lesion types can be used as diagnostic criteria for TBM in the paleopathological practice, they do not have the same diagnostic value. The first aim of the current paper is to further highlight the diagnostic value of GIs, ABVIs, PAs, and APDIs by calculating and discussing their diagnostic sensitivity and specificity estimate values, as well as their association with each other from the 427 identified pre‐antibiotic era skeletons of the Terry Collection. The second aim is to demonstrate three example cases from the Terry Collection, who exhibit bony changes on the inner skull surface that are representative of the macromorphological appearance and co‐occurrence of GIs, ABVIs, PAs, and APDIs (in different combinations). Based on the generated sensitivity and specificity estimate values, GIs are sufficient enough on their own to make a definitive diagnosis of TBM, whereas ABVIs, PAs, and APDIs are not specific to the disease but can be of tuberculous origin. The χ² test results regarding the association of ABVIs, PAs, and APDIs revealed that their co‐occurrence with each other (in any possible combination) is significantly more common in individuals who died of TB than in those who died of non‐TB causes—it implies that the chance of them being tuberculous in origin is higher when they simultaneously occur with each other. The three cases demonstrated in detail in the paper provide paleopathologists with a stronger basis for identifying TBM in ancient human remains that reveal endocranial alterations resembling that of the presented cases.

The perpetual burden of tuberculosis (TB) keeps drawing the focus of research on this disease. Among other risk factors (e.g., poor living conditions, malnutrition, smoking, HIV infection, etc.), being in close contact with a TB infected person requires special attention. For a better understanding of the disease, paleopathological investigations concerning TB have been carried out with various techniques for a long a time; nevertheless, analysis of incidence among family members is hardly possible in past populations. An exceptional group of naturally mummified individuals, the collection of the Vác mummies (Hungary, 18th century CE), is known about the large TB incidence rate, which has been revealed by aDNA analysis. Besides the high rate of TB infection, another interesting aspect of the collection is that in some cases, the family connections could be reconstructed. In this paper, we present the mycocerosic acid profiles gained by HPLC-HESI-MS measurements of two Vác mummies, who were mother and daughter according to the personal records. Earlier metagenomic analysis already revealed mixed M. tuberculosis infection with the same bacterial strains in both individuals; moreover, the same bacterial strains were recorded in both cases.

Abnormally pronounced digital impressions (APDIs) on the endocranial surface develop secondary to a prolonged rise in the intracranial pressure. This can result from a number of pathological conditions, including hydrocephalus due to tuberculous meningitis (TBM). APDIs have been described with relation to TBM not only in the modern medical literature but also in several paleopathological studies. However, APDIs are not pathognomonic for TBM and their diagnostic value for identifying TBM in past human populations has not been evaluated in identified pre-antibiotic era skeletons. To assess the diagnostic value of APDIs for the first time, a macroscopic investigation was performed on skeletons from the Terry Collection (Smithsonian Institution, Washington, DC, USA). Our material consisted of 234 skeletons with tuberculosis (TB) as the cause of death (TB group) and 193 skeletons with non-tuberculous (NTB) causes of death (NTB group). The macroscopic examination focused on the stage of the prominence and frequency of APDIs in the TB group and NTB group. To determine the significance of difference (if any) in the frequency of APDIs between the two groups, χ² testing of our data was conducted. We found that APDIs were twice as common in the TB group than in the NTB group. The χ² comparison of the frequencies of APDIs revealed a statistically significant difference between the two groups. In addition, APDIs with more pronounced stages were recorded more frequently in the TB group. Our results indicate that APDIs can be considered as diagnostic criteria for TBM in the paleopathological practice. With suitable circumspection, their utilization provides paleopathologists with a stronger basis for identifying TB and consequently, with a more sensitive means of assessing TB frequency in past human populations.