12 research outputs found
Perceptions of social care
Get PDFThe initial findings of a study evaluating the perspectives of learners and educators in higher education institutions (HEIs) in England.Unfunde
Beyond Repair Foci: DNA Double-Strand Break Repair in Euchromatic and Heterochromatic Compartments Analyzed by Transmission Electron Microscopy
Get PDFDNA double-strand breaks (DSBs) generated by ionizing radiation pose a serious threat to the preservation of genetic and epigenetic information. The known importance of local chromatin configuration in DSB repair raises the question of whether breaks in different chromatin environments are recognized and repaired by the same repair machinery and with similar efficiency. An essential step in DSB processing by non-homologous end joining is the high-affinity binding of Ku70-Ku80 and DNA-PKcs to double-stranded DNA ends that holds the ends in physical proximity for subsequent repair.Using transmission electron microscopy to localize gold-labeled pKu70 and pDNA-PKcs within nuclear ultrastructure, we monitored the formation and repair of actual DSBs within euchromatin (electron-lucent) and heterochromatin (electron-dense) in cortical neurons of irradiated mouse brain.While DNA lesions in euchromatin (characterized by two pKu70-gold beads, reflecting the Ku70-Ku80 heterodimer) are promptly sensed and rejoined, DNA packaging in heterochromatin appears to retard DSB processing, due to the time needed to unravel higher-order chromatin structures. Complex pKu70-clusters formed in heterochromatin (consisting of 4 or ≥ 6 gold beads) may represent multiple breaks in close proximity caused by ionizing radiation of highly-compacted DNA. All pKu70-clusters disappeared within 72 hours post-irradiation, indicating efficient DSB rejoining. However, persistent 53BP1 clusters in heterochromatin (comprising ≥ 10 gold beads), occasionally co-localizing with γH2AX, but not pKu70 or pDNA-PKcs, may reflect incomplete or incorrect restoration of chromatin structure rather than persistently unrepaired DNA damage.Higher-order organization of chromatin determines the accessibility of DNA lesions to repair complexes, defining how readily DSBs are detected and processed. DNA lesions in heterochromatin appear to be more complex, with multiple breaks in spatial vicinity inducing severe chromatin disruptions. Imperfect restoration of chromatin configurations may leave DSB-induced epigenetic memory of damage with potentially pathological repercussions
Major variation in hepatocellular carcinoma treatment and outcomes in England: a retrospective cohort study.
No full textObjectiveHepatocellular carcinoma (HCC) is increasingly incident in England, while survival remains poor with regional disparities. We aimed to explore the differences in HCC treatment across different geographical regions and to examine the impact on cancer survival.MethodsIncident HCC cases and treatment were identified from the English Hospital Episode Statistics (2016-2017) and then a subset by National Health Service (NHS) regions. Treatment was grouped into curative, palliative and untreated. Median survival was estimated to date of death in the national statistics.ResultsThe median observed survival was 8.6 months (95% CI 7.5 to 9.9) across all 2160 HCC cases, 52.1 months (CI 50.5, not reached) in 449 (20.8%) treated with curative intent, 21.0 months (CI 18.5 to 24.5) after other cancer-specific treatment in 449 (20.8%), and 2.3 months (CI 2.1 to 2.6) in 1262 (58.4%) untreated. Across NHS regions, ConclusionMajority of HCC cases in England are untreated and survival remains low, with variation in outcomes in regions with similar incident rates. A deeper exploration of regional treatments and screening practice is required to improve early detection and survival
Major variation in hepatocellular carcinoma treatment and outcomes in England: a retrospective cohort study
Full text linkObjectiveHepatocellular carcinoma (HCC) is increasingly incident in England, while survival remains poor with regional disparities. We aimed to explore the differences in HCC treatment across different geographical regions and to examine the impact on cancer survival.MethodsIncident HCC cases and treatment were identified from the English Hospital Episode Statistics (2016–2017) and then a subset by National Health Service (NHS) regions. Treatment was grouped into curative, palliative and untreated. Median survival was estimated to date of death in the national statistics.ResultsThe median observed survival was 8.6 months (95% CI 7.5 to 9.9) across all 2160 HCC cases, 52.1 months (CI 50.5, not reached) in 449 (20.8%) treated with curative intent, 21.0 months (CI 18.5 to 24.5) after other cancer-specific treatment in 449 (20.8%), and 2.3 months (CI 2.1 to 2.6) in 1262 (58.4%) untreated. Across NHS regions, <50% of cases received treatment (30.4%–49.6%), while between 14.2% and 27.7% had curative treatment. The 3-year survival was similar (23.5%–29.7%), except in the London region (40.0%).ConclusionMajority of HCC cases in England are untreated and survival remains low, with variation in outcomes in regions with similar incident rates. A deeper exploration of regional treatments and screening practice is required to improve early detection and survival.</jats:sec
Effect of Robot-Assisted Radical Cystectomy With Intracorporeal Urinary Diversion vs Open Radical Cystectomy on 90-Day Morbidity and Mortality Among Patients With Bladder Cancer
Full text linkATM Release at Resected Double-Strand Breaks Provides Heterochromatin Reconstitution to Facilitate Homologous Recombination
No full textWear protection of deep drawing tools by systematic optimization of highly stressed surfaces
No full textThe automotive sector is one of the largest energy consumers in Germany. Requests from politics and industry to significantly reduce emissions require new developments during utilization as well as during production phase. In line with the framework concept "InnoCaT", where more than 60 companies and research facilities from Germany take part, possibilities for producing companies are developed and analyzed to reduce the resource and energy consumption and by this reducing costs along the entire process chain of car body manufacturing. One approach to design car bodies lighter and more efficiently is to use aluminium and high strength steels. By this means weight and sheet thickness are reduced. However higher strengths of the steels and the adhesion affinity of aluminium significantly increase the requirements regarding the used tool steel. Thus grooves or galling appear more frequent at highly stressed surfaces. To assure high lifetimes and by this increase especially the resource efficiency concerning use of material and setting-up times within the press plant, a local optimization at the highly stressed surfaces is necessary. For this a FEM/BEM-tool for a time efficient and exact calculation of the occurring tool loads for complex die profiles is developed. Based on this development of load calculation a shape-optimization is performed at the corresponding areas. After the geometric optimization of the tool a local laser surface treatment for further wear protection is carried out using laser cladding or laser alloying/ -dispersing. By combining the technologies a highly wear resistant surface is achievable, which increases the tool's lifetime as well as the reproducibility within production
