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The jet stream is an important dynamic driver of climate variability in the Northern Hemisphere mid-latitudes 1-3 . Modern variability in the position of summer jet stream latitude in the North Atlantic-European sector (EU JSL) promotes dipole patterns in air pressure, temperature, precipitation and drought between northwestern and southeastern Europe. EU JSL variability and its impacts on regional climatic extremes and societal events are poorly understood, particularly before anthropogenic warming. Based on three temperature-sensitive European tree-ring records, we develop a reconstruction of interannual summer EU JSL variability over the period 1300-2004 CE (R 2  = 38.5%) and compare it to independent historical documented climatic and societal records, such as grape harvest, grain prices, plagues and human mortality. Here we show contrasting summer climate extremes associated with EU JSL variability back to 1300 CE as well as biophysical, economic and human demographic impacts, including wildfires and epidemics. In light of projections for altered jet stream behaviour and intensified climate extremes, our findings underscore the importance of considering EU JSL variability when evaluating amplified future climate risk., (© 2024. The Author(s).)

Significant regional variability in lifespan in Europe is influenced by environmental factors and lifestyle behaviors, including diet. This study investigates the impact of geographical region on the lifespan of European rulers spanning from the fourteenth century to the present day. By analyzing historical records and literature, we aim to identify region-specific dietary patterns and lifestyle factors that may have contributed to longer lifespans among rulers. The hypothesis to be tested is that rulers from Southern European countries, where the traditional Mediterranean diet is consumed by the local people, may exhibit longer lifespans compared to rulers from other regions, due to the well-documented health benefits associated with this dietary pattern. We extracted comprehensive information for each ruler, encompassing their sex, birth and death dates, age, age of enthronement, duration of rulership, country, and cause of death (natural vs. non-natural). To determine their nationality, we coded rulers based on their hypothetical present-day residence (2023). Utilizing the EuroVoc Geographical classification, we categorized the countries into four regions: Northern, Western, Southern, Central and Eastern Europe. While Cox regression models did not find significant differences in survival rates among regions, further analysis stratified by time periods revealed intriguing trends. Contrary to our initial predictions, the Northern region displayed better survival rates compared to the Southern region between 1354 and 1499, whereas survival rates were similar across regions from 1500 to 1749. However, after 1750, all regions, except the Southern region, exhibited significantly improved survival rates, suggesting advancements in healthcare and lifestyle factors. These findings underscore the dynamic influence of both region and time period on health and longevity. Interestingly, despite the prevalence of the Mediterranean diet in the Southern region of Europe, rulers from this region did not demonstrate longer lifespans compared to their counterparts in other regions. This suggests that additional lifestyle factors may have played a more prominent role in their longevity. In conclusion, our study sheds light on the intricate relationship between region, time period, and lifespan among European rulers. Although the Mediterranean diet is often associated with health benefits, our findings indicate that it alone may not account for differences in ruler longevity across regions. Further research is warranted to explore the impact of other lifestyle factors on the health and lifespan of European rulers throughout history., (© 2023. The Author(s).)

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus' expeditions 1,2 . Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico 3-6 . However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses., (© 2024. The Author(s).)

This chapter is limited to the text of Della Cruce, which contains the most comprehensive account of the instruments used in cranial surgery at the time. Of particular importance is Della Cruce's attitude to what he called non-perforating straight trepans, which in general he disliked. It may be noted that his text was the last to describe this sort of instrument. In the succeeding centuries, changes to penetrating instruments were all variations on the shape of different kinds of crown trepan. Like Berengario, Della Cruce described brace and bit trepans with interchangeable bits. Various methods were employed to prevent them penetrating too deeply., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The authors of the texts described in this chapter will have had access to the anatomy of Vesalius; a marked step forward. However, there was no equivalent advance in physiology. Harvey's book on the circulation of the blood was published in 1628 but it took many years for its contents to be accepted as standard teaching. The century saw the development of instruments some of which look more like instruments a modern surgeon would recognize. The two major technical advances were the acceptance of a single-handed trephine and the design of crown trepans with a conical shape and blades extending up the sides. Moreover, the crown trepan had once again become the favored instrument for gaining access to the interior of the cranium. In terms of technique there was a worrying trend that surgeons could feel when they had penetrated the inner table of the skull without the need to probe. All the way back to Hippocrates, it had been customary to use probes to assess depth while trepanning. Thus, the abandonment of this safety measure if it was real, is cause for concern. However, it is not impossible that probing was continued and simply not mentioned as it was so obviously necessary as not to require comment. The lenticular illustrated remains of the triangular shape first illustrated by Vidius. It is important to note that it was not used to incise the skull but to smooth of rough edges and spicules., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Realistic images became available for the first time. The first major figure was Berengario da Carpi (1460-1530). He made contributions to knowledge. He stated the dura was attached all over the interior of the cranium not just at the sutures. He also noted that deterioration following traumatic hematomas was speedier the deeper within the brain the bleed had occurred and he noticed that post-traumatic neurological deficits were contralateral. Moreover, he introduced new instruments of a practical design. Specifically, he launched trepanation using a brace and bit handle. This instrument required two hands and rotated the trepan in the same direction all the time. In addition, he illustrated a crown trepan in which the bits could be interchanged. He also developed an improved elevator. He also provided the first drawing of a lenticular. The next illustrations came from Vidus Vidius (1509-1569). The illustrations in his text were elegant and realistic but some of them were impractical or unusable. Ambroise Paré (1510-1590) was a major surgeon. He designed an improved brace and bit trepan with a collar to control penetration. He also introduced instruments for expanding a cranial opening by biting up the bone and for depressing the dura to enable material to escape more easily., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated 1 . Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age 2 , along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment., (© 2024. The Author(s).)

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity 1 . We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico 2-4 . Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions 1,5 . After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The identity of artists and localisation of workshops are rarely known with certainty before the mid-15th century. We investigated the material used by one of the most prolific and enigmatic medieval sculptors, the Master of the Rimini Altarpiece or Master of Rimini, active around 1420-40. The isotope fingerprints (Sr, S and O) of a representative corpus of masterpieces but also minor artworks, attributed to the Master of Rimini and his workshop, are virtually identical, demonstrating the unity of the corpus and a material evidence behind the stylistic and iconographic ascriptions. The material used is exclusively Franconian (N-Bavarian) alabaster, 600 km distant from the supposed zone of activity of the Master of Rimini workshop according to recent literature. The same material was later used by the prominent Late Medieval German carver Tilman Riemenschneider, active in Würzburg after 1483, whose small corpus of alabaster sculptures we have been able to characterize almost entirely. Based on these findings, we propose here an alternative to the prevailing hypothesis of a Flemish or N-French workshop being founded on similarities of the Rimini sculpture with motives in Flemish and French painting. Our scenario, returning to the initial proposal of a German localisation of the Master of Rimini workshop, assumes the migration of an artist, perhaps trained in the Low Countries or strongly inspired by the Flemish art, to Southern Germany where he founded a highly productive export workshop, well situated on the crossroads of medieval trade, with a pan-European radiance. This study sheds a spotlight on the on the trade networks of luxury goods, the raw material used for their production, and the high-end art market in Europe as well as on international migration of artists and styles, at the eve of the Renaissance., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Funding by Daniel Katz Gallery London of the analysis of one sample (Annunciation, bas-relief). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Present day scenario regarding epistemological methods in anatomy is in sharp contrast to the situation during ancient period. This study aimed to explore the evolution of epistemological methodologies in anatomy across centuries. In ancient times Egyptian embalmers acquired anatomical knowledge from handling human bodies and likewise anatomical studies in India involved human dissection. Ancient Greeks used theological principles-based methods, animal dissection and human dissection in practice of anatomy. Human dissection was also practiced in ancient China for gaining anatomical knowledge. Prohibition of human dissection led to use of animal dissection in ancient Rome and the trend continued in Europe through Middle Ages. Epistemological methods used by Muslim scholars during Middle Ages are not clearly chronicled. Human dissection returned as primary epistemological method in Renaissance Europe and empirical methods were reinstated after ancient period in human dissection during 16th century. The situation further improved with introduction of pragmatic experiment based approach during 17th century and autopsy-based methods during 18th century. Advances in anatomical knowledge continued with advent of microscope-based methods and emergence of anatomical sections in practice of human dissection in 19th century. Introduction of human observational studies, medical imaging, and molecular methods presented more options in terms of epistemological methods for investigating the human body during 20th century. Onset of 21st century has witnessed dominance of technology-based methods in anatomy. Limited emphasis on ethics in epistemological methodologies since antiquity is a dark aspect of otherwise an eventful evolutionary journey but recent developments are in positive direction., (© 2021 American Association for Anatomy.)

Over the last four millennia, the discipline of anatomy and its relationships with medicine and society have evolved dramatically. Human dissection, the perennial tool for anatomical discovery and education, has both guided this evolution and matured alongside it. Soon after the first cadaveric dissections recorded in ancient Greece, China, India, and Persia, clear endorsements of its practice fell largely silent in the anatomical record for 1,500 years before reappearing in Europe at the dawn of the Renaissance. Between the 13th and 18th centuries CE, the performance of anatomical dissection became a popular form of education and public entertainment, and the demand for human cadavers steadily increased among European anatomical schools while supply remained limited by legal statute. This gave rise to an informal group of amateur and professional body snatchers called the Resurrectionists and, later, inspired the Anatomy Act of 1832 CE. In the 20th and 21st centuries CE, voluntary body bequeathal programs have enabled the practice of human dissection to continue in academic centers as a cornerstone of anatomical education, now with a newfound focus on the development of affective skills. This article provides an abridged account of anatomy's development, highlighting key moments in its growth, the valuable contributions of many different societies to the discipline, and the important roles of several luminary anatomists of antiquity. Within the broader context of this history, it offers an overview of anatomical dissection's evocative past, spanning from its inception to its present-day practice., (© 2021 American Association for Anatomy.)

Ethnopharmacological Relevance: Theriac is considered the most popular cure-all multi-ingredient medicine and has been used for more than two millennia. It has also been used as one of the most important anti-epidemic drugs up to the 19th c., treated as an emergency medicine in case of e.g. bubonic plague., Aim of the Study: Until now, no reliable information regarding the pharmacological effect of the treacle was available, including its possible toxic or narcotic properties. In order to change the state of knowledge in this matter we have selected the Theriac recipe that had been actually used for producing the treacle in 1630, which was confirmed by the official municipal documents of the time., Methods: The recipe was written in Latin, with the use of pre-Linnean nomenclature and then apothecary common names, which required translation into the modern scientific language in order to get reliable pharmacological conclusions. The information from historical sources has been compiled with the pharmacological data concerning the most potent compounds, which for the first time made it possible to calculate the amounts of active compounds in the doses taken by then patients., Results: Only two species included in Theriac can be harmful in humans: poppy and sea squill, but in both cases the calculated quantity of morphine and cardiac glycosides, respectively, were below toxic level. There are no indications, both from the historical and pharmacological point of view, for Theriac being toxic or narcotic in patients, when used as prescribed., Conclusions: As for now, the most probable is that the treacle owed its postulated efficacy in the main indications to the placebo effect. Still, the results should be further confirmed by reconstructing the actual Theriac and subjecting it to modern tests and analyses., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Public health historians have repeatedly shown that the theory, policy, and practice of group prophylactics far predate their alleged birth in industrial modernity, and regularly draw on Galenic principles. While the revision overall has been successful, its main focus on European cities entails a major risk, since city dwellers were a minority even in Europe's most urbanised regions. At the same time, cities continue to be perceived and presented as typically European, which stymies transregional and comparative studies based at least in part on non- or extra-urban groups. Thus, any plan to both offer an accurate picture of public health's deeper past and fundamentally challenge a narrative of civilizational progress wedded to Euro-American modernity ("stagism") would benefit from looking beyond cities and their unique health challenges. The present article begins to do so by focusing on two ubiquitous groups, often operating outside cities and facing specific risks: miners and shipmates. Evidence for these communities' preventative interventions and the extent to which they drew on humoral theory is rich yet uneven for Europe between the thirteenth and sixteenth centuries. Methodological questions raised by this unevenness can be addressed by connecting different scales of evidence, as this article demonstrates. Furthermore, neither mining nor maritime trade was typically European, thus building a broader base for transregional studies and comparisons., (© The Author(s) 2021. Published by Oxford University Press.)

Oak wood was highly appreciated and widely used for construction in past centuries. As population sizes expanded in some regions of Europe, local forests were depleted of high-quality timber. Therefore, regions of soaring economies were importing timber initially from the European market and eventually from other continents. Origin of archaeological or historical timber is usually identified by means of dendroprovenancing, i.e. statistical matching of tree-ring-width (TRW) series of timber of unknown origin with TRW reference datasets. However, this method has pitfalls and limitations and therefore alternative techniques are needed. Here, we used three different DNA analysis methods to investigate the potential of using ancient (a)DNA, extracted from oak timber derived from historical buildings and shipwrecks from a variety of countries. All the material had also been analysed dendrochronologically, so its dating and provenance is demonstrated. We included heartwood samples in this analysis, for which DNA extraction is especially challenging as it contains chemicals that inhibit DNA amplification. We succeeded in amplifying DNA for at least one marker from 56% of samples (including heartwood samples), yielding crucial information that allowed us to identify the potential source area of centuries old timber buildings in Latvia and Denmark and of 750-year-old shipwreck material from Germany. Our results prove the strong potential of DNA analyses for identifying timber origin to the regional scale, but by combining these with the dendrochronological results, we can control the exactitude of the aDNA approach and demonstrate a more nuanced examination of the timber sources for these historic structures.

Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15 th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis' potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidum in early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws-causing T. pallidum subspecies were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws- and bejel-causing lineages. These findings imply a more complex pattern of geographical distribution and etiology of early treponemal epidemics than previously understood., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study outlines some understandings of the word "hygiene." The notion that originated in ancient Greece first began to be adopted as a system of diet and morals to prolong the lifespan. From a type of self-care, this idea transformed into a concept of governance to extend the lives of subject-citizens. The theoretical debate about what public hygiene used to be shows its eminently political side: not only was hygiene a branch of the political economy, the ideas of hygienists were also analyzed as to the degree of impact they had on policy. After political and scientific battles, certain understandings of government action emerged victorious, while others were forgotten and neglected.

Syphilis was perceived to be a new disease in Europe in the late 15th century, igniting a debate about its origin that continues today in anthropological, historical, and medical circles. We move beyond this age-old debate using an interdisciplinary approach that tackles broader questions to advance the understanding of treponemal infection (syphilis, yaws, bejel, and pinta). How did the causative organism(s) and humans co-evolve? How did the related diseases caused by Treponema pallidum emerge in different parts of the world and affect people across both time and space? How are T. pallidum subspecies related to the treponeme causing pinta? The current state of scholarship in specific areas is reviewed with recommendations made to stimulate future work. Understanding treponemal biology, genetic relationships, epidemiology, and clinical manifestations is crucial for vaccine development today and for investigating the distribution of infection in both modern and past populations. Paleopathologists must improve diagnostic criteria and use a standard approach for recording skeletal lesions on archaeological human remains. Adequate contextualization of cultural and environmental conditions is necessary, including site dating and justification for any corrections made for marine or freshwater reservoir effects. Biogeochemical analyses may assess aquatic contributions to diet, physiological changes arising from treponemal disease and its treatments (e.g., mercury), or residential mobility of those affected. Shifting the focus from point of origin to investigating who is affected (e.g., by age/sex or socioeconomic status) and disease distribution (e.g., coastal/ inland, rural/urban) will advance our understanding of the treponemal disease and its impact on people through time., (© 2020 Wiley Periodicals, Inc.)

Plague synchronously swept across separated regions in Europe throughout history. However, the spatio-temporal synchrony of plague and its driving mechanism have not been thoroughly investigated. In this study, we transformed the historical European plague database spanned 1347-1800 CE into country-level time-series that differentiated large-scale plague outbreak from counted data. We found that there are 74 years in which two or more countries in our study region (UK, France, Germany, Spain, and Italy) experienced large-scale plague outbreak in the same year. Our Multivariate Ripley's K-function results showed that the onset year and the cessation year of large-scale plague outbreak are synchronized at the 0-23-year and 0-20-year windows, respectively. The temporal association between such synchrony and climatic forcing was further investigated using the Superposed Epoch Analysis, and drought was found to be responsible for the synchrony. Integrating our results with a literature survey, we suggested that prior to the peak of plague, the occurrence of drought and the subsequent reintroduced rainfall dampened both the rodent community and human society and boosted the number of fleas that carried plague. Such a synthesis facilitated the outbreak of plague. At the same time, high temperature associated with such drought also confined the geographic diffusion of the plague. Hence, although continental mega-drought could initiate the synchrony of plague outbreak, the synchrony actually consisted of a number of localized plague outbreak events scattering across different regions in Europe. According to the projected rising trend of drought in terms of its magnitude, duration, and geographic extent, the risk of synchrony of rodent-borne diseases in Europe will be significantly elevated, especially in France, Italy, and Spain., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Astrologers have exercised self-censorship throughout the centuries in order to fend off criticism. This was largely for religious reasons, but social, political, and ethical motivations also have to be taken into account. This paper explores the main reasons that led astrologers to increase censorship in their writings in the decades that preceded the Church's regulations and offers some examples of this self-imposed restraint in astrological judgements.

Competing Interests: None

Background and Aims: Nucleotide Oligomerisation Domain 2 [NOD2] is a key gene of innate immunity which participates in the host defence against pathogens. Several loss-of-function NOD2 mutations are associated with Crohn's disease [CD]. Their high frequencies in populations of European ancestry suggest a model of balancing selection. Because NOD2 deficiency has been associated with a resistance to Yersinia pseudotuberculosis in mice, we hypothesised that NOD2 mutations have been selected during past plague outbreaks due to the closely related bacterium Yersinia pestis., Methods: Contemporary frequencies of the main CD-associated NOD2 mutations [R702W, G908R, and 1007fs], measured in healthy people from European and Mediterranean countries, were collected from 60 studies via a PubMed search. Plague exposure was calculated from a dataset providing outbreaks from 1346 to 1860 in Europe and the Mediterranean Bassin. A plague index was built to capture the intensity of plague exposure in the studied geographical areas., Results: NOD2 mutation frequencies were associated with the past exposure to plague. Statistical significance was obtained for the most frequent mutation [R702W, p = 0.03] and for the pooled three mutations [p = 0.023]. The association remained significant when putative demographic biases were considered., Conclusions: This result argues for a selection of CD-associated NOD2 mutations by plague outbreaks and further questioned the role of exposure to enteropathogenic Yersinia species in CD., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ethnopharmacological Relevance: In spite of the rich bio-cultural diversity found in the Neotropics relatively few herbal drugs native to South America are included in the global pharmacopoeia., Material and Methods: In the attempt to historically explain the inclusion of herbal drugs into official pharmacopoeias we consider the disparate epidemiology and cultural evolution of the New and the Old World. We then trace the development of pharmacopoeias and review forces that worked towards and against the synchronization of pharmacopoeias and highlight the role of early chemical and pharmacological studies in Europe. Finally, we compare the share of exotic and native herbal drug species included in the Brazilian Pharmacopoeia with the share of exotic and native species included in the European Pharmacopoeia as well as those used for products registered with ANVISA., Results: The domination of Eurasian herbal drugs in the European Pharmacopoeia seems to be conditioned by the geographical extension of Eurasia, which facilitated the interchange of materia medica and the creation of a consensus of use since ancient times. At the time of the Conquest the epidemiology of the Amerindian populations resembled that of pre-agriculturalist societies while no written consensus around efficacious medicine existed. Subsequently, introduced and well-tried plant species of the Old World gained therapeutic importance in the New World., Conclusion: The research focus in Europe and the US resulted in a persistence of herbal drugs with a historic importance in the European and US pharmacopoeias, which gained a status as safe and efficacious. During the last decades only few ethnopharmacological field-studies have been conducted with indigenous Amerindian groups living in the Brazilian Amazon, which might be attributable to difficulties in obtaining research permissions. Newly adopted regulations regarding access to biodiversity and traditional knowledge as well as the simplified procedure for licencing herbal medicinal products in Brazil prospects an interesting future for those aiming at developing herbal medicine based on bio-cultural diversity and respecting the protocols regulating benefit sharing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.

In historical times, plague epidemics intermittently ravaged Europe for more than 1,400 years, and still represent a threat in many countries all over the world. A debate is ongoing about the past plague, if it killed randomly in a population or discriminated among persons on the basis of their biological features. To address questions of plague lethality, we reviewed a large number of anthropological studies published in the last twenty years on victims of the past pestilences in Europe. In particular, we focused on data concerning demography (age at death and sex determination), and health status (skeletal biomarkers). We applied to these data a model system based on Multiple Linear Regression, which aimed to discern among possible predictors of sex-selective plague lethality in entire populations, in different periods and regions. Based on available data, we lack evidence for general trends of association between biological features. Differences in sex ratio are more likely due to the original population compositions or to distinct cultural behaviours of the two genders. We concluded that generalizations on biological evidence are not feasible for ancient plagues if we exclude that the infection possibly killed primarily persons between 5-10 and 20-35 years of age.

Syphilis is a chronic sexually transmitted disease (STD). At the end of the 15th century, Christopher Columbus imported it as "a souvenir" from his first voyage of discovery. The disease met a weakened and not yet infected population. The disease quickly engulfed all of Europe. The course of the disease was much more dramatic than it is today. Even royal houses were not spared. Using the example of Henry VIII of England this article briefly outlines the influence of syphilis both to the house of Tudor and thus on the big political stage.

"Health" is a positive multi-dimensional concept involving a variety of features, ranging from ability to integrity, from fitness to well-being. According to the first principle of the constitution of the World Health Organization "Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity". This constitution was adopted by the International Health Conference held in New York in June-July 1946 and became operative in April 1948. This classical, seventy-year old definition of the World Health Organization is nowadays considered a historical one and it stands as a fundamental milestone of a diachronic track beginning, in Western medicine, with the definition of health proposed by Hippocrates and his School. For Hippocrates health was the state of equilibrium of four humours. This philosophical-naturalistic definition has been flanked in the history of Western medicine by various concepts of health and disease, alternatively based, according to different scientists and in different medical contexts and periods, on epidemiological, anatomical, physiological, functional, social and molecular perspectives. Since biomedical definitions are always prone to integration and updating, depending on the continuous achievements of medical science and bioethics, the fascinating journey through the concepts of health and disease, the fundamental milestones of which are here briefly proposed, is still in progress.

It is generally accepted that human immunodeficiency virus (HIV) is the etiological agent of acquired immune deficiency syndrome. According to this claim, HIV was transferred to humans from contact with monkeys around 35-50 years ago. However, this claim has not been sufficiently confirmed epidemiologically. The spread and incubation period of the plague epidemic has led to the theory that the Black Death was caused by hemorrhagic viruses. Having examined detailed historical data, we have concluded that the bacterium Yersenia pestis was an infectious agent in the epidemic, together with another agent which we suggest was HIV. Our considerations were mainly based on the existence of the CCR5 delta 32 mutation, which protects against HIV infection and has been present in the Caucasian population for over 2000 years. The combination of two infectious agents led to the devastation of the Black Death, the removal of HIV carriers, and an increase in the number of CCR5Δ32 mutations in the Caucasian population. In sub-Saharan Africa, this epidemic and subsequent sanitation process did not occur, which explains the much higher level of HIV genetic information in this part of the world.

Europe's step-by-step approach to tackling canine and wildlife-mediated rabies has proven that the disease can be controlled and eliminated at the animal source. A decade of development work and support by the European Union has resulted in a successful oral rabies vaccination campaign for foxes and raccoon dogs, and provided the blueprint for eliminating wildlife-mediated rabies. In this paper, the authors examine the historical stages of animal rabies control and its eventual elimination in parts of Europe, particularly Western Europe. In addition, they consider current control measures and predict future challenges, many of which are faced by the vast and sparsely populated, rabies-endemic areas of Eastern Europe.

The last 50 years have seen the establishment of paediatric gastroenterology, hepatology, and nutrition (PGHAN) as a well-recognised and thriving clinical specialty throughout most of Europe, and further afield. This has happened, in part, through the existence of the European Society for Paediatric Gastroenterology and Nutrition (ESPGHAN) as a forum for those interested in this branch of children's medicine. To illustrate the pan-European roots of PGHAN, some key scientific and medical events, discoveries, and inventions relevant to 3 common clinical problems-diarrhoea, jaundice, and infant-feeding-have been chosen to survey the historical development of the ways in which each was understood and treated within the changing thinking and practice of past times. Together they are used to trace the prehistory of ESPGHAN and provide a background against which to explain the genesis of the Society and how its spheres of clinical and scientific interest came to be defined.

In this article, the authors present a historic overview of the development of medical education in the United States and Europe (in particular the Netherlands), as it relates to the issues of time (duration of the course) and proficiency (performance requirements and examinations). This overview is necessarily limited and based largely on post hoc interpretation, as historic data on time frames are not well documented and the issue of competence has only recently been addressed.During times when there were few, if any, formal regulations, physicians were primarily "learned gentlemen" in command of few effective practical skills, and the duration of education and the competencies acquired by the end of a course simply did not appear to be issues of any interest to universities or state authorities. Though uniform criteria gradually developed for undergraduate medical education, postgraduate specialty training remained, before accreditation organizations set regulations, at the discretion of individual institutions and medical societies. This resulted in large variability in training time and acquired competencies between residency programs, which were often judged on the basis of opaque or questionable criteria. Considering the high costs of health care today and the increasing demand for patient safety and educational efficiency, continuing historic models of nonstandardized practices will no longer be feasible. Efforts to constrain, restructure, and individualize training time and licensing tracks to optimize training for safe care, both in the United States and Europe, are needed.

Objectives: Suicide is a complex phenomenon determined by the interplay of an articulated network of factors including socio-economic factors which have a decisive role. This paper investigates the development of the modern conceptualization of suicide in Europe, its sociological understandings and its intertwinement with economic cycles throughout time., Methods: MEDLINE, SCHOLAR, EMBASE using the keywords 'socioeconomic factors AND suicide'; 'economic cycles AND suicide'; 'history AND suicide' without timeframe limitations. Moreover, journal-by-journal search in journals of related areas was performed., Results: In total, 51 historical studies focusing on the subjects in European countries were included. Three main areas arose: (a) development of the conceptualization of suicide over time; (b) sociological understandings of suicide according to the structure of society and its economy of power; (c) economic theories explaining the intertwinement of economic cycles and suicides., Conclusions: Suicide is a deeply human phenomenon inescapably linked to and grounded in society and economic cycles. Understandings from the past show the importance of accurate analysis of socio-economic contexts that shape societies together with man's own sense of self in order to organize multi-layered tangible and intangible support strategies to better understand and prevent suicide in this day and age.

Background: The history of human populations occupying the plains and mountain ridges separating Europe from Asia has been eventful, as these natural obstacles were crossed westward by multiple waves of Turkic and Uralic-speaking migrants as well as eastward by Europeans. Unfortunately, the material records of history of this region are not dense enough to reconstruct details of population history. These considerations stimulate growing interest to obtain a genetic picture of the demographic history of migrations and admixture in Northern Eurasia., Results: We genotyped and analyzed 1076 individuals from 30 populations with geographical coverage spanning from Baltic Sea to Baikal Lake. Our dense sampling allowed us to describe in detail the population structure, provide insight into genomic history of numerous European and Asian populations, and significantly increase quantity of genetic data available for modern populations in region of North Eurasia. Our study doubles the amount of genome-wide profiles available for this region. We detected unusually high amount of shared identical-by-descent (IBD) genomic segments between several Siberian populations, such as Khanty and Ket, providing evidence of genetic relatedness across vast geographic distances and between speakers of different language families. Additionally, we observed excessive IBD sharing between Khanty and Bashkir, a group of Turkic speakers from Southern Urals region. While adding some weight to the "Finno-Ugric" origin of Bashkir, our studies highlighted that the Bashkir genepool lacks the main "core", being a multi-layered amalgamation of Turkic, Ugric, Finnish and Indo-European contributions, which points at intricacy of genetic interface between Turkic and Uralic populations. Comparison of the genetic structure of Siberian ethnicities and the geography of the region they inhabit point at existence of the "Great Siberian Vortex" directing genetic exchanges in populations across the Siberian part of Asia. Slavic speakers of Eastern Europe are, in general, very similar in their genetic composition. Ukrainians, Belarusians and Russians have almost identical proportions of Caucasus and Northern European components and have virtually no Asian influence. We capitalized on wide geographic span of our sampling to address intriguing question about the place of origin of Russian Starovers, an enigmatic Eastern Orthodox Old Believers religious group relocated to Siberia in seventeenth century. A comparative reAdmix analysis, complemented by IBD sharing, placed their roots in the region of the Northern European Plain, occupied by North Russians and Finno-Ugric Komi and Karelian people. Russians from Novosibirsk and Russian Starover exhibit ancestral proportions close to that of European Eastern Slavs, however, they also include between five to 10 % of Central Siberian ancestry, not present at this level in their European counterparts., Conclusions: Our project has patched the hole in the genetic map of Eurasia: we demonstrated complexity of genetic structure of Northern Eurasians, existence of East-West and North-South genetic gradients, and assessed different inputs of ancient populations into modern populations.

Separation of pharmacy from medicine induced the requirements formulation for an ideal pharmacist. Two prominent authors did so, Saladin di Ascoli (the first half of the XVth century) in the work Compendium aromatariorum (1488) and Valerius Cordus (1515-1544) in the work Dispensatorium pharmacopolarum (1546). Both of them formulate similar postulates of both professional and ethical nature, namely a knowledge of Latin, good education, experience, good character traits, need of satisfied marriage; both say that the pharmacist is required to be a good Christian, they condemn alcohol, relationships with women, poisons and abortifacients, remember right relationship to money. In addition, Cordus adds a good financial situation. Their considerations had a great impact on further development of pharmacy across Europe.Key words: Saladin di Ascoli Valerius Cordus ideal pharmacist.

Plague, a deadly zoonose caused by the bacterium Yersinia pestis, has been firmly documented in 39 historical burial sites in Eurasia that date from the Bronze Age to two historical pandemics spanning the 6th to 18th centuries. Palaeomicrobiologic data, including gene and spacer sequences, whole genome sequences and protein data, confirmed that two historical pandemics swept over Europe from probable Asian sources and possible two-way-ticket journeys back from Europe to Asia. These investigations made it possible to address questions regarding the potential sources and routes of transmission by completing the standard rodent and rodent-flea transmission scheme. This suggested that plague was transmissible by human ectoparasites such as lice, and that Y. pestis was able to persist for months in the soil, which is a source of reinfection for burrowing mammals. The analyses of seven complete genome sequences from the Bronze Age indicated that Y. pestis was probably not an ectoparasite-borne pathogen in these populations. Further analyses of 14 genomes indicated that the Justinian pandemic strains may have formed a clade distinct from the one responsible for the second pandemic, spanning in Y. pestis branch 1, which also comprises the third pandemic strains. Further palaeomicrobiologic studies must tightly connect with historical and anthropologic studies to resolve questions regarding the actual sources of plague in ancient populations, alternative routes of transmission and resistance traits. Answering these questions will broaden our understanding of plague epidemiology so we may better face the actuality of this deadly infection in countries where it remains epidemic., (Copyright © 2016. Published by Elsevier Ltd.)

Ancient DNA analysis has revealed an involvement of the bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14(th) century Black Death until the mid-18(th) century AD). Here we present reconstructed Y. pestis genomes from plague victims of the Black Death and two subsequent historical outbreaks spanning Europe and its vicinity, namely Barcelona, Spain (1300-1420 cal AD), Bolgar City, Russia (1362-1400 AD), and Ellwangen, Germany (1485-1627 cal AD). Our results provide support for (1) a single entry of Y. pestis in Europe during the Black Death, (2) a wave of plague that traveled toward Asia to later become the source population for contemporary worldwide epidemics, and (3) the presence of an historical European plague focus involved in post-Black Death outbreaks that is now likely extinct., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Plague has been responsible for two major historic pandemics (6th-8th century CE; 14th-19th century CE) and a modern one. The recent Malagasy plague outbreaks raised new concerns on the deadly potential of the plague-causing bacteria Yersinia pestis. Between September 2014 and April 2015, outbreaks of bubonic and pneumonic plague hit the Malagasy population. Two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. The scope of our study was to ascertain whether the risk factors for health in modern-day populations exposed to plague and in ancient populations that faced the two historic pandemics varied or remained substantially unaltered., Methodology: The risk of mortality of the Malagasy population with those obtained from the reconstruction of three samples of European populations exposed to the historic pandemics was contrasted., Results: The evidence shows that the risks of death are not uniform across age neither in modern nor in historic populations exposed to plague and shows precise concentrations in specific age groups (children between five and nine years of age and young adults)., Conclusions: Although in the post-antibiotic era, the fatality rates have drastically reduced, both modern and historic populations were exposed to the same risk factors that are essentially represented by a low standard of environmental hygiene, poor nutrition, and weak health systems.

The 14th-18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague's persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death.

Ancient DNA (aDNA) recovered from plague victims of the second plague pandemic (14th to 17th century), excavated from two different burial sites in Germany, and spanning a time period of more than 300 years, was characterized using single nucleotide polymorphism (SNP) analysis. Of 30 tested skeletons 8 were positive for Yersinia pestis-specific nucleic acid, as determined by qPCR targeting the pla gene. In one individual (MP-19-II), the pla copy number in DNA extracted from tooth pulp was as high as 700 gene copies/μl, indicating severe generalized infection. All positive individuals were identical in all 16 SNP positions, separating phylogenetic branches within nodes N07_N10 (14 SNPs), N07_N08 (SNP s19) and N06_N07 (s545), and were highly similar to previously investigated plague victims from other European countries. Thus, beside the assumed continuous reintroduction of Y. pestis from central Asia in multiple waves during the second pandemic, long-term persistence of Y. pestis in Europe in a yet unknown reservoir host has also to be considered.