Author
Rachel Clarke
Bio: Rachel Clarke is an academic researcher from University of Oxford. The author has contributed to research in topics: Etoricoxib & Population. The author has an hindex of 7, co-authored 10 publications receiving 343 citations.
Topics: Etoricoxib, Population, Iron Age, Medicine, Cancer
Papers
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TL;DR: Using rarecoal, a new method, it is estimated that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain.
Abstract: British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain.
144 citations
TL;DR: Single-dose oral etoricoxib produces high levels of good quality pain relief after surgery, and adverse events did not differ from placebo in these studies, and the 120 mg dose is as effective as, or better than, other commonly used analgesics.
Abstract: Background Etoricoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor licensed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis, and acute pain in some jurisdictions. This class of drugs is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). One additional study in acute postoperative pain has been published since the original review was completed in Issue 2, 2009. Objectives To assess the analgesic efficacy and adverse effects of a single oral dose of etoricoxib for moderate to severe postoperative pain. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. The date of the most recent search was 3 January 2012. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of single dose, oral etoricoxib for acute postoperative pain in adults. Data collection and analysis Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed etoricoxib or placebo with at least 50% pain relief over six hours, using validated equations. We calculated relative risk (RR) and number needed to treat to benefit (NNT). We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. Main results One additional study has been added to this updated review, making a total of six included studies with 1214 participants in comparisons of etoricoxib with placebo. All six studies reported on the 120 mg dose (798 participants in a comparison with placebo). At least 50% pain relief was reported by 66% with etoricoxib 120 mg and 12% with placebo (NNT 1.8 (1.7 to 2.0)). For dental studies only the NNT was 1.6 (1.5 to 1.8). Although the new study almost doubled the number of participants in included studies it added only about 25% more data for the 120 mg dose and the result was unchanged. Other doses (60, 90, 180, and 240 mg) were each studied in only one treatment arm and we did not undertake pooled analysis.Significantly fewer participants used rescue medication over 24 hours when taking etoricoxib 120 mg than placebo (NNT to prevent remedication 2.2 (1.9 to 2.8)), and the median time to use of rescue medication was 20 hours for etoricoxib and two hours for placebo. Adverse events were reported at a similar rate to placebo, with no serious events. Authors' conclusions The additional study did not change the results from the first review published in 2009, but does make the result more robust. Single dose oral etoricoxib produces high levels of good quality pain relief after surgery and adverse events did not differ from placebo. The 120 mg dose is as effective as, or better than, other commonly used analgesics.
107 citations
TL;DR: Over 50% of children with leukaemia have palpable livers, palpable spleens, pallor, fever or bruising on diagnosis, and common abdominal symptoms such as anorexia, weight loss, abdominal pain and abdominal distension are common.
Abstract: OBJECTIVE: Leukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all existing data on its clinical presentation and estimated the frequency of signs and symptoms presenting at or prior to diagnosis. DESIGN: We searched MEDLINE and EMBASE for all studies describing presenting features of leukaemia in children (0-18 years) without date or language restriction, and, when appropriate, meta-analysed data from the included studies. RESULTS: We screened 12 303 abstracts for eligibility and included 33 studies (n=3084) in the analysis. All were cohort studies without control groups. 95 presenting signs and symptoms were identified and ranked according to frequency. Five features were present in >50% of children: hepatomegaly (64%), splenomegaly (61%), pallor (54%), fever (53%) and bruising (52%). An additional eight features were present in a third to a half of children: recurrent infections (49%), fatigue (46%), limb pain (43%), hepatosplenomegaly (42%), bruising/petechiae (42%), lymphadenopathy (41%), bleeding tendency (38%) and rash (35%). 6% of children were asymptomatic on diagnosis. CONCLUSIONS: Over 50% of children with leukaemia have palpable livers, palpable spleens, pallor, fever or bruising on diagnosis. Abdominal symptoms such as anorexia, weight loss, abdominal pain and abdominal distension are common. Musculoskeletal symptoms such as limp and joint pain also feature prominently. Children with unexplained illness require a thorough history and focused clinical examination, which should include abdominal palpation, palpation for lymphadenopathy and careful scrutiny of the skin. Occurrence of multiple symptoms and signs should alert clinicians to possible leukaemia.
84 citations
TL;DR: In this article, the Max Planck Society, the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (771234-PALEoRIDER, to W.H., 805268-CoDisEASe to K. Bos; 834616-ARCHCAUCASUS to S.H. and AP08857177 to A.Z.
Abstract: The research was funded by the Max Planck Society, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (771234–PALEoRIDER, to W.H.; 805268–CoDisEASe to K. Bos; 834616–ARCHCAUCASUS to S.H.), the Slovak Academy of Sciences and the European Union’s Seventh Framework Programme and Marie Curie Actions under the Programme SASPRO (1340/03/03 to P.C.R.), the ERA.NET RUS Plus–ST 19-78-10053 to SSh), the German Research Foundation (DFG-HA-5407/4-1–INTERACT to W.H. and RE2688/2 to S.Re.), the French National Research Agency (ANR-17-FRAL-0010–INTERACT, to M.F.D., M.Ri., S.Ro., S.Sai., D.Bi., and P.Le.), the Wenner-Gren Dissertation Fieldwork Grant (9558 to S.Sab.), and the Ministry of Education and Science of the Republic of Kazakhstan (AP08856654 to L.B.D., L.M., and E.Kh. and AP08857177 to A.Z.B.).
30 citations
TL;DR: Today’s British are more similar to the Iron Age individuals than to most of the Anglo-Saxon individuals, and it is estimated that the contemporary East English population derives 30% of its ancestry from Anglo- Saxon migrations, with a lower fraction in Wales and Scotland.
Abstract: British population history has been shaped by a series of immigrations and internal movements, including the early Anglo-Saxon migrations following the breakdown of the Roman administration after 410CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences generated from ten ancient individuals found in archaeological excavations close to Cambridge in the East of England, ranging from 2,300 until 1,200 years before present (Iron Age to Anglo-Saxon period). We use present-day genetic data to characterize the relationship of these ancient individuals to contemporary British and other European populations. By analyzing the distribution of shared rare variants across ancient and modern individuals, we find that today’s British are more similar to the Iron Age individuals than to most of the Anglo-Saxon individuals, and estimate that the contemporary East English population derives 30% of its ancestry from Anglo-Saxon migrations, with a lower fraction in Wales and Scotland. We gain further insight with a new method, rarecoal, which fits a demographic model to the distribution of shared rare variants across a large number of samples, enabling fine scale analysis of subtle genetic differences and yielding explicit estimates of population sizes and split times. Using rarecoal we find that the ancestors of the Anglo-Saxon samples are closest to modern Danish and Dutch populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain.
27 citations
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TL;DR: Advances in understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease.
1,362 citations
01 Jan 2009
TL;DR: This chapter is dedicated to the preparation of ALL samples for cytogenetic and FISH analysis, with emphasis on the modifications to standard protocols which may be used to improve their quality.
Abstract: Cytogenetics plays an important role in the diagnosis of acute lymphoblastic leukaemia (ALL), particularly in relation to the association of specific chromosomal abnormalities with outcome. The karyotype at diagnosis is used in the risk stratification of patients for treatment within trial-based protocols. Chromosomal analysis of the leukaemic cells of patients with ALL is challenging as the mitotic index may be low and the chromosomal morphology is often poor. Therefore, the use of fluorescence in situ hybridisation (FISH) in parallel with cytogenetic analysis is important for the detection of those chromosomal abnormalities of prognostic significance. This chapter is dedicated to the preparation of ALL samples for cytogenetic and FISH analysis, with emphasis on the modifications to standard protocols which may be used to improve their quality. The specific difficulties encountered in the analysis of ALL metaphases and suggestions for overcoming them are provided. The chapter also includes an overview of the abnormalities that are expected to be found in this disease and how the results from both cytogenetics and FISH should be interpreted.
732 citations
Harvard University1, Broad Institute2, University of Tübingen3, Max Planck Society4, University of Mainz5, University of Washington6, University of California, Berkeley7, Massachusetts Institute of Technology8, Stockholm University9, University of Adelaide10, The Heritage Foundation11, National Museum of Natural History12, University of Edinburgh13, Sultan Qaboos University14, University of Costa Rica15, University of Antioquia16, Rambam Health Care Campus17, University of Pécs18, Al Akhawayn University19, Catholic University of the Sacred Heart20, University of Oxford21, Belgorod State University22, University of Toronto23, University of Buenos Aires24, University of Bern25, Russian Academy of Sciences26, Paul Sabatier University27, North-Eastern Federal University28, University of Chicago29, University of Arizona30, Stony Brook University31, University of Bergen32, Illumina33, Sofia Medical University34, Bashkir State University35, University of Cambridge36, Vilnius University37, Estonian Biocentre38, University of Strasbourg39, University College London40, Amgen41, Gladstone Institutes42, University of Tartu43, University of Oulu44, Muhimbili University of Health and Allied Sciences45, University of Palermo46, University of Chile47, University of Tarapacá48, Academy of Sciences of Uzbekistan49, Armenian National Academy of Sciences50, University of North Texas51, University of Santiago de Compostela52, University of Kharkiv53, Higher University of San Andrés54, Novosibirsk State University55, Leidos56, Lebanese American University57, University of Split58, University of Pennsylvania59, Banaras Hindu University60, Centre for Cellular and Molecular Biology61, Estonian Academy of Sciences62, Pompeu Fabra University63, Howard Hughes Medical Institute64
TL;DR: The authors showed that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunters-gatherer related ancestry.
Abstract: We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
442 citations
Harvard University1, Howard Hughes Medical Institute2, Broad Institute3, University of Zaragoza4, Max Planck Society5, University of Huddersfield6, University of Minho7, Pompeu Fabra University8, University of Vienna9, Pennsylvania State University10, University of Coimbra11, University of Zurich12, University of Granada13, University of the Basque Country14, Rovira i Virgili University15, National University of Distance Education16, University of Málaga17, University of Barcelona18, University of Valencia19, Autonomous University of Barcelona20, University of Lisbon21, Facultad de Filosofía y Letras22, University of Cádiz23, University of Almería24, University of Salamanca25, University of Iowa26, University of Las Palmas de Gran Canaria27, Mount Mercy University28, Autonomous University of Madrid29, Complutense University of Madrid30, University of Cantabria31, Liverpool John Moores University32, Gibraltar Hardware33, Anglia Ruskin University34, Spanish National Research Council35, University of California, Santa Barbara36, Danube Private University37, University of Basel38, University of Adelaide39
TL;DR: It is revealed that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia, and how the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean is document.
Abstract: J.M.F., F.J.L.-C., J.I.M., F.X.O., J.D., and M.S.B. were supported by HAR2017-86509-P, HAR2017-87695-P, and SGR2017-11 from the Generalitat de Catalunya, AGAUR agency. C.L.-F. was supported by Obra Social La Caixa and by FEDER-MINECO (BFU2015- 64699-P). L.B.d.L.E. was supported by REDISCO-HAR2017-88035-P (Plan Nacional I+D+I, MINECO). C.L., P.R., and C.Bl. were supported by MINECO (HAR2016-77600-P). A.Esp., J.V.-V., G.D., and D.C.S.-G. were supported by MINECO (HAR2009-10105 and HAR2013-43851-P). D.J.K. and B.J.C. were supported by NSF BCS-1460367. K.T.L., A.W., and J.M. were supported by NSF BCS-1153568. J.F.-E. and J.A.M.-A. were supported by IT622-13 Gobierno Vasco, Diputacion Foral de Alava, and Diputacion Foral de Gipuzkoa. We acknowledge support from the Portuguese Foundation for Science and Technology (PTDC/EPH-ARQ/4164/2014) and the FEDER-COMPETE 2020 project 016899. P.S. was supported by the FCT Investigator Program (IF/01641/2013), FCT IP, and ERDF (COMPETE2020 – POCI). M.Si. and K.D. were supported by a Leverhulme Trust Doctoral Scholarship awarded to M.B.R. and M.P. D.R. was supported by an Allen Discovery Center grant from the Paul Allen Foundation, NIH grant GM100233, and the Howard Hughes Medical Institute. V.V.-M. and W.H. were supported by the Max Planck Society.
287 citations