An osteoarchaeological reconstruction of the medieval population from the Hospital of St James at Thornton Abbey, Lincolnshire

This thesis examines the Hospital of St James at Thornton Abbey, Lincolnshire, looking at funerary practice and the hospital's population. This is the first examination of the hospital since excavations at the site closed in 2016. The primary objective of the thesis is to characterise the Hospital of St James. This is achieved through a multidisciplinary approach, incorporating osteology, population demography and archaeological research methods which provide a broad and reaching approach to the archaeological assemblage enabling a comprehensive study to take place. The thesis begins with an introduction to the role of a hospital in later medieval society, commenting on the principals upon which they were founded, their contribution to charity and their position on the edge of monastic and lay communities. Having established the background to the role hospitals fulfilled in later medieval England, the aim of characterising the Hospital of St James is first addressed through an exploration of the burial practices carried out at the hospital. The thesis goes on to address this objective through the establishment and exploration of the population's demographic profile which reveals a dominantly male population with a large proportion of non-adults. This demographic profile is compared to nine contemporary hospital sites to integrate the Hospital of St James into current literature concerning medieval hospitals of England, as well as monastic and lay populations as a means to explore the extent to which the hospital represented the monastic communities from which they were established. Following this an exploration of the palaeopathologies present in the cemetery is undertaken and also compared to the nine contemporary hospitals. Through this, the type of care being ordered at the Hospital of St James can be measured against that being ordered at other hospitals. The penultimate chapter presents a discussion surrounding the large number of non-adults present within the hospital's assemblage, calling for a discussion of the position of children in medieval society and their relationship with the religious communities of later medieval England. This draws upon the involvement of religious communities in caring for sick and abandoned children, their role as a primary educator and their training children for a life of monasticism. The discussion also examines the location of the Hospital of St James within the outer precinct of Thornton Abbey, and how this position may have had an influence upon the large presence of non-adults and the role the hospital fulfilled. The final chapter discusses the characterisation of the Hospital of St James established from the thesis research findings. These finding conclude that the Hospital of St James may not have followed the convention of the four hospital types referenced throughout academic literature, instead it displays a complex blend of children, the sick poor and corrodians. Following these, suggestions for future research is presented regarding the further study of late medieval hospital demographic profiles and the research potential of the skeletal assemblage from the Hospital of St James

Bloodstain classification methods: A critical review and a look to the future

Classifying bloodstains is an essential part of Bloodstain Pattern Analysis. Various experts have developed methods. Each method considers the same basic bloodstain pattern types. These use either terminology based on the observable characteristics or the mechanistic cause of the bloodstains as part of the classification process. This review paper considers ten classification methods from fourteen sources, which are used to classify bloodstain patterns. There are fundamental differences in how the bloodstains are classified, how differentiated the classification is, and whether the classification process uses clear, unambiguous criteria, and is susceptible to contextual bias. Experts have also reported issues with classifying bloodstains that have indistinguishable features. These differences expose key limitations with current classification methods: mechanistic terminology is too heavily relied on, and the classification process is susceptible to contextual bias. The development of an unambiguous classification method, based on directly observable characteristics within bloodstain patterns is recommended for future work

Bloodstain classification methods: A critical review and a look to the future

Classifying bloodstains is an essential part of Bloodstain Pattern Analysis. Various experts have developed methods. Each method considers the same basic bloodstain pattern types. These use either terminology based on the observable characteristics or the mechanistic cause of the bloodstain patterns as part of the classification process. This review paper considers ten classification methods from fourteen sources, which are used to classify bloodstain patterns. There are fundamental differences in how the patterns are classified, how differentiated the classification is, and whether the classification process uses clear, unambiguous criteria, and is susceptible to contextual bias. Experts have also reported issues with classifying bloodstains that have indistinguishable features. These differences expose key limitations with current classification methods: mechanistic terminology is too heavily relied on, and the classification process is susceptible to contextual bias. The development of an unambiguous classification method, based on directly observable characteristics within bloodstain patterns is recommended for future work

Health Utility Analysis of Tepotinib in Patients with Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping

OBJECTIVES: The VISION trial showed durable activity of tepotinib in MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC). We analyzed health state utilities using patient-reported outcomes from VISION. METHODS: EQ-5D-5L and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 responses were collected at baseline, every 6-12 weeks during treatment, and at end-of-treatment and safety follow-up. EQ-5D-5L and EORTC Quality of Life Utility Measure-Core 10 Dimensions (QLU-C10D) utilities were derived using US, Canada, UK and Taiwan value sets, where available. Utilities were analyzed with linear mixed models including covariates for progression or time-to-death (TTD). RESULTS: Utilities were derived for 273/291 patients (EQ-5D-5L, 1545 observations; QLU-C10D, 1546 observations). Mean (± standard deviation) US EQ-5D-5L utilities increased after tepotinib initiation, from 0.687 ± 0.287 at baseline to 0.754 ± 0.250 before independently assessed progression, and decreased post-progression (0.704 ± 0.288). US QLU-C10D utilities showed similar trends (0.705 ± 0.215, 0.753 ± 0.195, and 0.708 ± 0.209, respectively). Progression-based models demonstrated a statistically significant impact of progression on utilities and predicted higher utilities pre- versus post-progression. TTD-based models showed statistically significant associations of TTD with utilities and predicted declining utilities as TTD decreased. Prior treatment (yes/no) did not significantly predict utilities in progression- or TTD-based models. Utilities for Canada, UK and Taiwan showed comparable trends. CONCLUSIONS: In this first analysis of health state utilities in patients with METex14 skipping NSCLC, who received tepotinib, utilities were significantly associated with progression and TTD, but not prior treatment

Exploring the spectral diversity of low-redshift Type Ia supernovae using the Palomar Transient Factory

We present an investigation of the optical spectra of 264 low-redshift (z < 0.2) Type Ia supernovae (SNe Ia) discovered by the Palomar Transient Factory, an untargeted transient survey. We focus on velocity and pseudo-equivalent width measurements of the Si II 4130, 5972, and 6355 A lines, as well those of the Ca II near-infrared (NIR) triplet, up to +5 days relative to the SN B-band maximum light. We find that a high-velocity component of the Ca II NIR triplet is needed to explain the spectrum in ~95 per cent of SNe Ia observed before -5 days, decreasing to ~80 per cent at maximum. The average velocity of the Ca II high-velocity component is ~8500 km/s higher than the photospheric component. We confirm previous results that SNe Ia around maximum light with a larger contribution from the high-velocity component relative to the photospheric component in their Ca II NIR feature have, on average, broader light curves and lower Ca II NIR photospheric velocities. We find that these relations are driven by both a stronger high-velocity component and a weaker contribution from the photospheric Ca II NIR component in broader light curve SNe Ia. We identify the presence of C II in very-early-time SN Ia spectra (before -10 days), finding that >40 per cent of SNe Ia observed at these phases show signs of unburnt material in their spectra, and that C II features are more likely to be found in SNe Ia having narrower light curves.Comment: 18 page, 10 figures, accepted for publication in MNRA

An operational analysis of Lake Surface Water Temperature

Operational analyses of Lake Surface Water Temperature (LSWT) have many potential uses including improvement of numerical weather prediction (NWP) models on regional scales. In November 2011, LSWT was included in the Met Office Operational Sea Surface Temperature and Ice Analysis (OSTIA) product, for 248 lakes globally. The OSTIA analysis procedure, which has been optimised for oceans, has also been used for the lakes in this first version of the product. Infra-red satellite observations of lakes and in situ measurements are assimilated. The satellite observations are based on retrievals optimised for Sea Surface Temperature (SST) which, although they may introduce inaccuracies into the LSWT data, are currently the only near-real-time information available. The LSWT analysis has a global root mean square difference of 1.31 K and a mean difference of 0.65 K (including a cool skin effect of 0.2 K) compared to independent data from the ESA ARC-Lake project for a 3-month period (June to August 2009). It is demonstrated that the OSTIA LSWT is an improvement over the use of climatology to capture the day-to-day variation in global lake surface temperatures

Cells of the human intestinal tract mapped across space and time

Acknowledgements We acknowledge support from the Wellcome Sanger Cytometry Core Facility, Cellular Genetics Informatics team, Cellular Generation and Phenotyping (CGaP) and Core DNA Pipelines. This work was financially supported by the Wellcome Trust (W1T20694, S.A.T.; 203151/Z/16/Z, R. A. Barker.); the European Research Council (646794, ThDefine, S.A.T.); an MRC New Investigator Research Grant (MR/T001917/1, M.Z.); and a project grant from the Great Ormond Street Hospital Children’s Charity, Sparks (V4519, M.Z.). The human embryonic and fetal material was provided by the Joint MRC/Wellcome (MR/R006237/1) Human Developmental Biology Resource (https://www.hdbr.org/). K.R.J. holds a Non-Stipendiary Junior Research Fellowship from Christ’s College, University of Cambridge. M.R.C. is supported by a Medical Research Council Human Cell Atlas Research Grant (MR/S035842/1) and a Wellcome Trust Investigator Award (220268/Z/20/Z). H.W.K. is funded by a Sir Henry Wellcome Fellowship (213555/Z/18/Z). A.F. is funded by a Wellcome PhD Studentship (102163/B/13/Z). K.T.M. is funded by an award from the Chan Zuckerberg Initiative. H.H.U. is supported by the Oxford Biomedical Research Centre (BRC) and the The Leona M. and Harry B. Helmsley Charitable Trust. We thank A. Chakravarti and S. Chatterjee for their contribution to the analysis of the enteric nervous system. We also thank R. Lindeboom and C. Talavera-Lopez for support with epithelium and Visium analysis, respectively; C. Tudor, T. Li and O. Tarkowska for image processing and infrastructure support; A. Wilbrey-Clark and T. Porter for support with Visium library preparation; A. Ross and J. Park for access to and handling of fetal tissue; A. Hunter for assistance in protocol development; D. Fitzpatrick for discussion on developmental intestinal disorders; and J. Eliasova for the graphical images. We thank the tissue donors and their families, and the Cambridge Biorepository for Translational Medicine and Human Developmental Biology Resource, for access to human tissue. This publication is part of the Human Cell Atlas: https://www.humancellatlas.org/publications.Peer reviewedPublisher PD

Cells of the human intestinal tract mapped across space and time.

Funder: Medical Research CouncilThe cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease