Author
Cyrus Cooper
Other affiliations: University of Oxford, University of York, University of Potsdam ...read more
Bio: Cyrus Cooper is an academic researcher from Southampton General Hospital. The author has contributed to research in topics: Population & Osteoporosis. The author has an hindex of 204, co-authored 1869 publications receiving 206782 citations. Previous affiliations of Cyrus Cooper include University of Oxford & University of York.
Topics: Population, Osteoporosis, Hip fracture, Cohort study, Bone density
Papers published on a yearly basis
Papers
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TL;DR: Fracture incidence was increased in children using inhaled corticosteroids, as well as in those receiving bronchodilators alone, and this excess risk disappeared after adjustment for indicators of asthma severity.
Abstract: Inhaled corticosteroids are widely used in the long-term management of asthma in children. Data on the relationship between inhaled corticosteroid therapy and osteoporotic fracture are inconsistent. We address this issue in a large population-based cohort of children aged 4-17 years in the UK (the General Practice Research Database). The incidence rates of fracture among children aged 4-17 years taking inhaled corticosteroids (n=97,387), taking bronchodilators only (n=70 984) and a reference group (n=345,758) were estimated. Each child with a non-vertebral fracture (n=23,984) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. Fracture incidence was increased in children using inhaled corticosteroids, as well as in those receiving bronchodilators alone. With an average daily beclomethasone dose of 200 microg or less, the crude fracture risk relative to nonusers was 1.10 [95% confidence interval (CI), 0.96-1.26]; with dosage of 201-400 microg, it was 1.23 (95% CI, 1.08-1.39); and with dosages over 400 microg, it was 1.36 (95% CI, 1.11-1.67). This excess risk disappeared after adjustment for indicators of asthma severity. The increased risk of fracture associated with use of inhaled corticosteroids is likely to be the result of the underlying illness, rather than being directly attributable to inhaled corticosteroid therapy.
84 citations
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TL;DR: A classification for the causes of raised BMD is outlined, based on identification of focal or generalized BMD changes, and an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history is discussed.
Abstract: A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.
84 citations
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TL;DR: This study undertook the present study in order to identify central sensitization using neuroimaging and PainDETECT and to relate it to postarthroplasty outcome.
Abstract: OBJECTIVE The neural mechanisms of pain in knee osteoarthritis (OA) are not fully understood, and some patients have neuropathic-like pain associated with central sensitization. To address this, we undertook the present study in order to identify central sensitization using neuroimaging and PainDETECT and to relate it to postarthroplasty outcome. METHODS Patients awaiting arthroplasty underwent quantitative sensory testing, psychological assessment, and functional magnetic resonance imaging (fMRI). Neuroimaging (fMRI) was conducted during punctate stimulation (n = 24) and cold stimulation (n = 20) to the affected knee. The postoperative outcome was measured using the Oxford Knee Score, patient-reported moderate-to-severe long-term pain postarthroplasty, and a range of pain-related questionnaires. RESULTS Patients with neuropathic-like pain presurgery (identified using PainDETECT; n = 14) reported significantly higher pain in response to punctate stimuli and cold stimuli near the affected joint (P < 0.05). Neural activity in these patients, compared to those without neuropathic-like pain, was significantly lower in the rostral anterior cingulate cortex (P < 0.05) and higher in the rostral ventromedial medulla (RVM) during punctate stimulation (P < 0.05), with significant functional connectivity between these two areas (r = 0.49, P = 0.018). Preoperative neuropathic-like pain and higher neural activity in the RVM were associated with moderate-to-severe long-term pain after arthroplasty (P = 0.0356). CONCLUSION The psychophysical and neuroimaging data suggest that a subset of OA patients have centrally mediated pain sensitization. This was likely due to supraspinally mediated reductions in inhibition and increases in facilitation of nociceptive signaling, and was associated with a worse outcome following arthroplasty. The neurobiologic confirmation of central sensitization in patients with features of neuropathic pain, identified using PainDETECT, provides further support for the investigation of such bedside measures for patient stratification, to better predict postsurgical outcomes.
84 citations
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TL;DR: This work has provided the first experimental evidence for a novel transport system which provides net amino acid transport to the fetus and influences fetal growth.
Abstract: Fetal growth depends on placental transfer of amino acids from maternal to fetal blood. The mechanisms of net amino acid efflux across the basal membrane (BM) of the placental syncytiotrophoblast to the fetus, although vital for amino acid transport, are poorly understood. We examined the hypothesis that facilitated diffusion by the amino acid transporters TAT1, LAT3 and LAT4 plays an important role in this process, with possible effects on fetal growth. Amino acid transfer was measured in isolated perfused human placental cotyledons (n = 5 per experiment) using techniques which distinguish between different transport processes. Placental TAT1, LAT3 and LAT4 proteins were measured, and mRNA expression levels (measured using real-time quantitative-PCR) were related to fetal and neonatal anthropometry and dual-energy X-ray absorptiometry measurements of neonatal lean mass in 102 Southampton Women's Survey (SWS) infants. Under conditions preventing transport by amino acid exchangers, all amino acids appearing in the fetal circulation were substrates of TAT1, LAT3 or LAT4. Western blots demonstrated the presence of TAT1, LAT3 and LAT4 in placental BM preparations. Placental TAT1 and LAT3 mRNA expression were positively associated with measures of fetal growth in SWS infants (P < 0.05). We provide evidence that the efflux transporters TAT1, LAT3 and LAT4 are present in the human placental BM, and may play an important role in the net efflux of amino acids to the fetus. Unlike other transporters they can increase fetal amino acid concentrations. Consistent with a role in placental amino acid transfer capacity and fetal growth TAT1 and LAT3 mRNA expression showed positive associations with infant size at birth.
84 citations
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University of Cambridge1, Beth Israel Deaconess Medical Center2, Sir Charles Gairdner Hospital3, King's College London4, University of Western Australia5, McGill University6, University of Iceland7, Arthritis Research UK8, University of Queensland9, University of Gothenburg10, University of Edinburgh11, University of Cantabria12, John Hunter Hospital13, University of Jyväskylä14, University of Southampton15, University of Lübeck16, University of Graz17, Harokopio University18, Boston University19, Erasmus University Rotterdam20, University of Pittsburgh21, University of California, San Francisco22, California Pacific Medical Center23, Wellcome Trust Sanger Institute24, National Institutes of Health25, University of Split26, University of Helsinki27, University of Hong Kong28, Wageningen University and Research Centre29, University of Tampere30, Turku University Hospital31, University of Turku32, Uppsala University33, Hallym University34, Greifswald University Hospital35, University of Sheffield36, Menzies Research Institute37, University of Auckland38, Royal Melbourne Hospital39, Katholieke Universiteit Leuven40, Manchester Academic Health Science Centre41, University of Oxford42, VU University Medical Center43, Oulu University Hospital44, University of Florence45, Wake Forest University46, Lund University47, Royal Brisbane and Women's Hospital48, Laval University49, Oregon Health & Science University50
TL;DR: This GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
Abstract: Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
83 citations
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28,685 citations
28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
01 Jan 2016
TL;DR: The using multivariate statistics is universally compatible with any devices to read, allowing you to get the most less latency time to download any of the authors' books like this one.
Abstract: Thank you for downloading using multivariate statistics. As you may know, people have look hundreds times for their favorite novels like this using multivariate statistics, but end up in infectious downloads. Rather than reading a good book with a cup of tea in the afternoon, instead they juggled with some harmful bugs inside their laptop. using multivariate statistics is available in our digital library an online access to it is set as public so you can download it instantly. Our books collection saves in multiple locations, allowing you to get the most less latency time to download any of our books like this one. Merely said, the using multivariate statistics is universally compatible with any devices to read.
14,604 citations
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TL;DR: Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chair person) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK)
13,400 citations
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TL;DR: The role of vitamin D in skeletal and nonskeletal health is considered and strategies for the prevention and treatment ofitamin D deficiency are suggested.
Abstract: Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.
11,849 citations