19 research outputs found

    Genetic history of Cambridgeshire before and after the Black Death.

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    The extent of the devastation of the Black Death pandemic (1346-1353) on European populations is known from documentary sources and its bacterial source illuminated by studies of ancient pathogen DNA. What has remained less understood is the effect of the pandemic on human mobility and genetic diversity at the local scale. Here, we report 275 ancient genomes, including 109 with coverage >0.1×, from later medieval and postmedieval Cambridgeshire of individuals buried before and after the Black Death. Consistent with the function of the institutions, we found a lack of close relatives among the friars and the inmates of the hospital in contrast to their abundance in general urban and rural parish communities. While we detect long-term shifts in local genetic ancestry in Cambridgeshire, we find no evidence of major changes in genetic ancestry nor higher differentiation of immune loci between cohorts living before and after the Black Death

    Pathways to the medieval hospital : Collective osteobiographies of poverty and charity

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    Medieval hospitals were founded to provide charity, but poverty and infirmity were broad and socially determined categories and little is known about the residents of these institutions and the pathways that led them there. Combining skeletal, isotopic and genetic data, the authors weave a collective biography of individuals buried at the Hospital of St John the Evangelist, Cambridge. By starting with the physical remains, rather than historical expectations, they demonstrate the varied life courses of those who were ultimately buried in the hospital's cemetery, illustrating the diverse faces of medieval poverty and institutional notions of charity. The findings highlight the value of collective osteobiography when reconstructing the social landscapes of the past

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    East Anglian Early Neolithic monument burial linked to contemporary Megaliths

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    In the fourth millennium BCE a cultural phenomenon of monumental burial structures spread along the Atlantic façade. Megalithic burials have been targeted for aDNA analyses, but a gap remains in East Anglia where Neolithic structures were generally earthen or timber. An early Neolithic (3762 – 3648 cal. BCE) burial monument at the site of Trumpington Meadows, Cambridgeshire, U.K. contained the partially articulated remains of at least three individuals. To determine whether this monument fits a pattern present in megalithic burials regarding sex bias, kinship, diet, and relationship to modern populations, teeth and ribs were analysed for DNA and carbon and nitrogen isotopic values respectively. Whole ancient genomes were sequenced from two individuals to a mean genomic coverage of 1.6 and 1.2X and genotypes imputed. Results show that they were brothers from a small population genetically and isotopically similar to previously published British Neolithic individuals, with a level of genome-wide homozygosity consistent with a small island population sourced from continental Europe, but bearing no signs of recent inbreeding. The first Neolithic whole genomes from a monumental burial in East Anglia confirm that this region was connected with the larger pattern of Neolithic megaliths in the British Isles and the Atlantic façade.This work is supported by the Wellcome Trust (Award no. 2000368/Z/15/Z) and St John's College, Cambridge (J.E.R., T.K., R.H., S.A.I, A.R., T.C.O’C., C.C.); the European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.16-0030) (C.L.S.); and the Estonian Research Council personal research grant (PRG243) (C.L.S). E.D’A was supported by Sapienza University of Rome fellowship “borsa di studio per attività di perfezionamento all’estero 2017”

    Osteobiography: The History of the Body as Real Bottom-Line History.

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    What is osteobiography good for? The last generation of archaeologists fought to overcome the traditional assumption that archaeology is merely ancillary to history, a substitute to be used when written sources are defective; it is now widely acknowledged that material histories and textual histories tell equally valid and complementary stories about the past. Yet the traditional assumption hangs on implicitly in biography: osteobiography is used to fill the gaps in the textual record rather than as a primary source in its own right. In this article we compare the textual biographies and material biographies of two thirteenth-century townsfolk from medieval England-Robert Curteis, attested in legal records, and "Feature 958," excavated archaeologically and studied osteobiographically. As the former shows, textual biographies of ordinary people mostly reveal a few traces of financial or legal transactions. Interpreting these traces, in fact, implicitly presumes a history of the body. Osteobiography reveals a different kind of history, the history of the body as a locus of appearance and social identity, work, health and experience. For all but a few textually rich individuals, osteobiography provides a fuller and more human biography. Moreover, textual visibility is deeply biased by class and gender; osteobiography offers particular promise for Marxist and feminist understandings of the past.status: publishe

    East Anglian early Neolithic monument burial linked to contemporary Megaliths

    No full text
    In the fourth millennium BCE a cultural phenomenon of monumental burial structures spread along the Atlantic façade. Megalithic burials have been targeted for aDNA analyses, but a gap remains in East Anglia, where Neolithic structures were generally earthen or timber. An early Neolithic (3762-3648 cal. BCE) burial monument at the site of Trumpington Meadows, Cambridgeshire, UK, contained the partially articulated remains of at least three individuals. To determine whether this monument fits a pattern present in megalithic burials regarding sex bias, kinship, diet and relationship to modern populations, teeth and ribs were analysed for DNA and carbon and nitrogen isotopic values, respectively. Whole ancient genomes were sequenced from two individuals to a mean genomic coverage of 1.6 and 1.2X and genotypes imputed. Results show that they were brothers from a small population genetically and isotopically similar to previously published British Neolithic individuals, with a level of genome-wide homozygosity consistent with a small island population sourced from continental Europe, but bearing no signs of recent inbreeding. The first Neolithic whole genomes from a monumental burial in East Anglia confirm that this region was connected with the larger pattern of Neolithic megaliths in the British Isles and the Atlantic façade.status: publishe

    Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers

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    Radiation exposure at a young age is a strong risk factor for thyroid cancer. We conducted a nested case-control study of 69 thyroid cancer cases and 265 controls from a cohort of 14,054 childhood cancer survivors to evaluate the shape of the radiation dose-response relationship, in particular at high doses, and to assess modification of the radiation effects by patient and treatment characteristics. We considered several types of statistical models to estimate the excess relative risk (ERR), mainly guided by radiobiological models. A two-parameter model with a term linear in dose and a negative exponential in dose squared provided the best parsimonious description with an ERR of 1.3 per gray (95% confidence interval 0.4-4.1) at doses below 6 Gy and a relative decrease in ERR of 0.2% per unit dose squared with increasing dose, that is, decreases in the ERR/Gy of 53% at 20 Gy and 95% at 40 Gy. Further analyses using spline models suggested that the significant nonlinearity at high doses was characterized most appropriately as a true downturn rather than a flattening of the dose-response curve. We found no statistically significant modification of the dose-response relationship by patient characteristics; however, the linear parameter (i.e., the ERR/ Gy at doses less than 6 Gy) did decrease consistently and linearly with increasing age at childhood cancer diagnosis, from 4.45 for 0-1-year-olds to 0.48 for 15-20-year-olds. In summary, we applied models derived from radiobiology to describe the radiation dose-response curve for thyroid cancer in an epidemiological study and found convincing evidence for a downturn in risk at high dose
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