3,405 research outputs found
"Historian of the spirit": an introduction to the life and ideas of Christopher H. Dawson, 1889-1970
Full text linkWhat follows is an intellectual biography of the English Catholic historian Christopher Henry Dawson (1889-1970). If there is one overarching thesis to this dissertation, it is that Dawson's place within the history of Britain and the United States and within the historical academy in general has been hitherto underappreciated as a result of unfair categorization of his work by critics, and equally unhelpful credulous assessments imd subsequent politicization of his scholarship by overzealous admirers. Even though his perspectives will probably never be completely embraced by the historical academy due to current trends in historiography, it is hoped that this dissertation will demonstrate that Dawson’s scholarship is deserving of study because of the breadth of his intellectual and practical activity in Britain during the twentieth century, and his groundbreaking role in identifying the importance of culture and religious belief to historiography. The introduction includes a review of the most important secondary literature about Dawson that will be used throughout the work. The main text of the dissertation develops chronologically, and is in eight parts, each part representing a distinct phase of Dawson's life. Part Chie (1889-1914) examines the formative years of his childhood, his education, his conversion to the Roman Catholic Church, and how his experiences formed the basis for his opinions about history, religion, and world around him. Part Two (1915-1929) explores the schools of thought that shaped Dawson’s ideas as a young scholar, and the ideas expressed in his first two books. Part Three (1930-1934) represents the most active time of Dawson's career, and the period during which he became a widely read Catholic intellectual and historian of Europe. Part Four (1935-1939) examines Dawson's commentaries on European political movements during the 1930ร. Part Five (1940-1945) discusses Dawson's role as the vice-president of die wartime ecumenical movement 'The Sword of the Spirit', as well as his book written at the height of the Movement's success. Part Six (1946-1952) covers Dawson's ideas from his Gifford Lectures, and his interest in American Catholicism. Part Seven (1953-1962) covers Dawson's vision for American Catholics and education, and his position at Harvard University, which he held from 1958 until a series of strokes forced him to retire, and return to England in 1962. Part Eight (1963-1970) briefly discussed the events of the last years of his life. The conclusion serves as a summary of his contribution and legacy as a major twentieth-century intellectual
"The 'fightin'est' Canadian general:" Brigadier Christopher Vokes and his approach to military command, June 1942 -- August 1943
No full textThis thesis evaluates the manner in which Brigadier Christopher Yokes dealt with the technical and human aspects of command while commanding the 2nd Canadian Infantry Brigade from 25 June 1942 until the end of the Sicilian campaign in August 1943. It seeks to promote a greater understanding of brigade-level command and to rehabilitate Vokes's reputation as a commander, which has largely been based on certain negative personality traits. The author argues that Yokes was a successful commander because he maintained a good balance between technical skills such as planning and directing operations and his ability to understand, motivate, and lead soldiers, and because his actions were guided by a sound philosophy of command based on personal leadership and teamwork. These elements allowed Christopher Yokes to train and lead a highly effective and cohesive fighting force that defeated some of Germany's best troops in the physically demanding environment of the Sicilian battlefield
"The 'fightin'est' Canadian general:" Brigadier Christopher Vokes and his approach to military command, June 1942 -- August 1943
No full textThis thesis evaluates the manner in which Brigadier Christopher Yokes dealt with the technical and human aspects of command while commanding the 2nd Canadian Infantry Brigade from 25 June 1942 until the end of the Sicilian campaign in August 1943. It seeks to promote a greater understanding of brigade-level command and to rehabilitate Vokes's reputation as a commander, which has largely been based on certain negative personality traits. The author argues that Yokes was a successful commander because he maintained a good balance between technical skills such as planning and directing operations and his ability to understand, motivate, and lead soldiers, and because his actions were guided by a sound philosophy of command based on personal leadership and teamwork. These elements allowed Christopher Yokes to train and lead a highly effective and cohesive fighting force that defeated some of Germany's best troops in the physically demanding environment of the Sicilian battlefield
Abstract IA8: The genetics and genomics of African esophageal cancer
No full textAbstract
Esophageal squamous cell carcinoma (ESCC) is common in many Black populations of sub-Saharan Africa, with high incidence regions in Eastern and Southern Africa. Clinical presentation in Africa is late, and treatment is mainly palliative with a very poor prognosis. Various environmental risk factors have been identified, but the possible contribution of inherited genetic variants to disease risk is an important question which is unresolved. Also, limited data are available on the somatic mutations which are driving tumor development. This presentation will review current knowledge on the role of germline genetic variants and somatic mutations in the development of African ESCC.
Genetic association studies of African ESCC have been limited to the analysis of small numbers of single nucleotide polymorphisms (SNPs) in candidate genes, and carried out only in the Black and Mixed Ancestry populations of the Western Cape of South Africa. Several positive associations have been reported, particularly in the Mixed Ancestry population, but none have achieved genome-wide levels of significance or been replicated in independent studies. We are currently testing SNPs which have been associated with ESCC in genome-wide association studies (GWAS) from Asian and European populations for association with ESCC in the South African population. Black cases with a histologically confirmed diagnosis of ESCC and matching population controls were recruited, after informed consent and institutional ethical approval, from the Western Cape and Gauteng provinces of South Africa. SNPs were genotyped either by individual TaqMan assays (Applied Biosystems) or in a multiplex MassARRAY (Agena Bioscience) and genotypes were tested for association. Our initial studies found no significant evidence of association at previously reported GWAS loci ATP1B2, CASP8, c20orf54, HEATR3, PDE4D, PLCE1, PTPN2, RUNX1, SMG6, ST6GAL1, TMEM173 and UNC5L loci. However, evidence for association was observed for the SNP rs2239815 at XBP1 on chromosome 22q12 (OR =1.41, P = 0.00087), and the SNPs rs4822983 (OR = 1.31, P = 0.0013) and rs1033667 (OR = 1.29, P = 0.0025) in CHEK2. Genotyping of a larger SNP panel in an expanded collection of cases and controls is in progress to extend these findings.
Detection of somatic mutations in ESCC tumour tissue has in the past been limited to sequencing of candidate genes and copy number studies, with TP53 mutations being detected in a minority of South African and Kenyan patients. We have carried out pilot whole exome sequencing in 10 matched blood/tumour pairs from South African ESCC patients and detected mutations in TP53, ATR, GNAS, MAGI2, FBXW7, FLT3, NFE2L2, TET2 and ZNF750. Follow up sequencing of the TP53 gene detected missense or truncating mutations in 18/26 (69%) of tumours. A recent sequencing study of 59 Malawian ESCC patients (Liu et al) observed recurrent mutations in TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1 and FBXW7, and transcriptomic profiles were used to divide ESCCs into 3 subtypes.
Priorities for the future should include well powered GWAS in high risk populations from several African countries, with collaborative studies to compare genetic risk factors across populations and meta-analysis to provide power to detect risk loci with moderate effects. Whole-exome or whole genome sequencing of substantial panels of blood/tumour pairs are needed to establish the major drivers of tumorigenesis in African ESCC and to derive mutational signatures which may provide insight into causal environmental factors.
Citation Format: Christopher G. Mathew. The genetics and genomics of African esophageal cancer [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA8.</jats:p
Founders: Christopher Taylor
Full text link\ua9 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. ‘Founders’ is an intermittent series of short, critical appreciations of scholars, researchers and others whose work and ideas, mainly in Britain, have made particularly sweeping, influential and foundational contributions to the development of historically- and archaeologically-informed landscape studies. This latest addition to the series concerns Christopher Taylor, whose death on 28th May 2021 was noted in the Landscapes editorial in issue 21.2
Letter to the Editor: 1H and 15N chemical shift assignments for domain 4 of the common beta-chain of the IL-3, IL-5 and GM-CSF receptors
No full textTerrence D. Mulhern, Christopher J. Bagley, Craig Gaunt, Angel.F. Lopez, Mathew A. Vadas, Richard J. D'Andrea, Grant W. Booke
Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes
No full textOsteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring “bystander” cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin-1 (Panx1) channels to release adenosine diphosphate (ATP) as a “find me” signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue-loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF-kB ligand (RANKL) expression and osteoclastic bone resorption in wild-type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X7R in ATP release; thus, we examined P2X7R-deficient mice and WT mice treated with P2X7R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find-me signal. P2X7RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1 KO and P2X7RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X7R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process.Peer reviewe
The effects of estrogen deficiency on cortical bone microporosity and mineralization
No full textRecent studies have demonstrated matrix-mineral alterations in bone tissue surrounding osteocytes in estrogen-deficient animals.While cortical bone porosity has been shown to be a contributor to the mechanical properties of bone tissue, little analysis has been done to investigate the effects of estrogen deficiency on bone's microporosities, including the vascular and osteocyte lacunar porosities. In this study we examined alterations in cortical bone microporosity, mineralization, and cancellous bone architecture due to estrogen deficiency in the ovariectomized rat model of postmenopausal osteoporosis. Twenty-week-old female Sprague–Dawley rats were subjected to either ovariectomy or sham surgery. Six weeks post-surgery tibiae were analyzed using high-resolution micro-CT, backscattered electron imaging, nanoindentation, and dynamic histomorphometry. Estrogen deficiency caused an increase in cortical bone vascular porosity, with enlarged vascular pores and little change in tissue mineral density in the proximal tibial metaphysis. Measurements of cancellous architecture corresponded to previous studies reporting a decrease in bone volume fraction, an increase in trabecular separation, and a decrease in trabecular number in the proximal tibia due to estrogen deficiency. Nanoindentation results showed no differences in matrix stiffness in osteocyte-rich areas of the proximal tibia of estrogen-deficient rats, and bone labeling and backscattered electron imaging showed no significant changes in mineralization around the vascular pores. The findings demonstrate local surface alterations of vascular pores due to estrogen deficiency. An increase in cortical vascular porosity may diminish bone strength as well as alter bone mechanotransduction via interstitial fluid flow, both of which could contribute to bone fragility during postmenopausal osteoporosis.Peer reviewe
Heritability and Linkage Analysis of Appendicitis Utilizing Age at Onset
Get PDFAppendicitis usually afflicts the young, but there is a large tail in the distribution of onset age. The genetics of this disease are still not well understood. A heritability analysis and genome wide linkage analysis of a large twin dataset was undertaken. Treating age of onset of appendicitis as a censored survival trait revealed a heritability of 0.21, and found evidence of linkage to Chromosome 1p37.3. Author(s): Christopher Oldmeadow 1 * | Kerrie Mengersen 2 | Nicholas Martin 3 | David L. Duffy
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