38 research outputs found

    Civilian Evacuation to Devon in the Second World War

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    Extensive sources have been reviewed and analysed to piece together for the first time a detailed academic study of civilian evacuation to Devon viewed against the national backdrop. The primary focus of this thesis is the large number of unaccompanied children who were officially evacuated to the County under the auspices of the Government Evacuation Scheme during the Second World War. However, Chapter Six discusses the evacuation of mothers and accompanying children, unofficial (private) evacuees and private school parties. The majority of evacuated children arriving in Devon originated from the London area and southeastern counties. In addition large numbers of children were also evacuated to the County from Bristol and within the County from Plymouth (Devon) during 1941 and briefly from Exeter in May 1942. Each of the three national evacuation waves is considered individually throughout the text as they are quite distinct in complexion, a fact frequently ignored in generalised accounts which tend to focus on reaction to the initial wave. This thesis argues that: 1. lack of regional and local research has resulted in evacuation largely being viewed in generalised and stereotypical terms without due regard for the socioeconomic and geopolitical variance between those areas involved or the particular localised features of the evacuation process 2. the acclimatisation of evacuated children was particularly successful in Devon and drift back less than the national average 3. local evidence supports the argument that contemporary national reports of impoverished, dirty and ill mannered evacuees were frequently exaggerated 4. evacuation was central in accelerating postwar reform in areas of education, child care and welfare The civilian evacuation during World War Two was a remarkable event in the history of modern Britain. Interest in the subject has recently increased but there is enormous scope and need for further research both to broaden our understanding of the nature and impact of evacuation and to test entrenched views. The over-arching aim of this thesis is to contribute to this exploration

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

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    Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Civilian evacuation to Devon in the Second World War

    No full text
    Extensive sources have been reviewed and analysed to piece together for the first time a detailed academic study of civilian evacuation to Devon viewed against the national backdrop. The primary focus of this thesis is the large number of unaccompanied children who were officially evacuated to the County under the auspices of the Government Evacuation Scheme during the Second World War. However, Chapter Six discusses the evacuation of mothers and accompanying children, unofficial (private) evacuees and private school parties. The majority of evacuated children arriving in Devon originated from the London area and southeastern counties. In addition large numbers of children were also evacuated to the County from Bristol and within the County from Plymouth (Devon) during 1941 and briefly from Exeter in May 1942. Each of the three national evacuation waves is considered individually throughout the text as they are quite distinct in complexion, a fact frequently ignored in generalised accounts which tend to focus on reaction to the initial wave. This thesis argues that: 1. lack of regional and local research has resulted in evacuation largely being viewed in generalised and stereotypical terms without due regard for the socioeconomic and geopolitical variance between those areas involved or the particular localised features of the evacuation process 2. the acclimatisation of evacuated children was particularly successful in Devon and drift back less than the national average 3. local evidence supports the argument that contemporary national reports of impoverished, dirty and ill mannered evacuees were frequently exaggerated 4. evacuation was central in accelerating postwar reform in areas of education, child care and welfare The civilian evacuation during World War Two was a remarkable event in the history of modern Britain. Interest in the subject has recently increased but there is enormous scope and need for further research both to broaden our understanding of the nature and impact of evacuation and to test entrenched views. The over-arching aim of this thesis is to contribute to this exploration.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
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