The COLO-COHORT (Colorectal Cancer Cohort) study: Protocol for a multi-centre, observational research study and development of a consent-for-contact research platform

Aim The COLO-COHORT study aims to produce a multi-factorial risk prediction model for colorectal neoplasia that can be used to target colonoscopy to those at greatest risk of colorectal neoplasia, ensuring that people are not investigated unnecessarily and maximizing the use of limited endoscopy resources. The study will also explore the link between neoplasia and the human gut microbiome. Additionally, the study aims to generate a cohort of colonoscopy patients who are ‘research ready’ through the development of a consent-for-contact (C4C) platform, to facilitate a range of colorectal cancer prevention studies to be conducted at scale and speed. Methods and analysis This is a multi-centre observational study involving sites across the UK. Recruitment is over a 6-year period (2019–2025). Patients recruited to the study are those attending for colonoscopy. Patients are recruited into two groups, namely observational group A (10 000 patients) and C4C group B (10 000 patients), known as COLO-SPEED (Colorectal Cancer Screening Prevention Endoscopy and Early Diagnosis; https://colospeed.uk). Patients complete a health questionnaire, provide anthropometric measurements and submit biosamples (blood and stool—depending on the part of the study they are recruited into). Patients' colonoscopy and histology findings are also recorded. Models of factors associated with the presence of neoplasia at colonoscopy will be developed using logistic or multinomial regression. For internal validation, model discrimination and calibration will be assessed and bootstrapping and cross-validation approaches used. To enable long-term follow-up for outcomes related to colorectal cancer and polyps, patients are asked to consent to follow-up through data linkage with national databases. Dissemination In keeping with good research practice, following analysis by the study team the study investigators will make the anonymized dataset available to other researchers. The C4C platform will also be accessible to other researchers. The study findings will be submitted for publication in peer-reviewed journals and lay summaries will be disseminated to participants and the wider public

Preaching to the choir: patterns of non/diversity in youth citizenship movements

Within many youth-focused or youth-led civic and political action groups in the UK, a common discursive refrain is the importance of promoting equality and diversity in politics in order to empower the participation of marginalised young people and communities. This chapter explores the dynamics of diversity in two youth-led UK political groups, in order to understand rhetorical positions and material outcomes of organisational commitments to prioritising diversity. Reflecting on the implications of the contrasting ‘diversity’ repertoires of both organisations (Momentum and My Life My Say), this chapter explores how economic, social and historical contexts inflect youth citizenship spaces and suggests how strategies for effective diversification of youth citizenship movements can begin to expand possibilities for meaningful inclusion practices in youth politics

ERP Conceptual Ecology

The technological evolution of recent years has made that information systems frequently adapt to the market realities to fulfill the improvements of the company’s organizational processes. In this context, new paradigms, approaches, and concepts were disseminated through the new realities of information systems. This study aims to verify how ERP (Enterprise Resource Planning) has been related to other information systems within its ecosystem. For this purpose, we have reviewed the literature based on 650 publications whose central theme was the ERP. The data were treated through a graphical analysis, inspired by SNA (Social Network Analysis), represented by related ERP concepts. The study results, determine the connection degree between the concepts that emerged with the technological evolution and the ERP, thus representing the ERP interoperability tendencies, over the last years. The study concludes that ERPs have been improving and substantially increasing the conditions of nteroperability with other information systems and with new organizational concepts that have emerged through the technological availability. This fact led to a better organizational process’s adoption and more organizational performance.info:eu-repo/semantics/publishedVersio

Large-scale mass wasting in the western Indian Ocean constrains onset of East African rifting

Faulting and earthquakes occur extensively along the flanks of the East African Rift System, including an offshore branch in the western Indian Ocean, resulting in remobilization of sediment in the form of landslides. To date, constraints on the occurrence of submarine landslides at margin scale are lacking, leaving unanswered a link between rifting and slope instability. Here, we show the first overview of landslide deposits in the post-Eocene stratigraphy of the Tanzania margin and we present the discovery of one of the biggest landslides on Earth: the Mafia mega-slide. The emplacement of multiple landslides, including the Mafia mega-slide, during the early-mid Miocene is coeval with cratonic rifting in Tanzania, indicating that plateau uplift and rifting in East Africa triggered large and potentially tsunamigenic landslides likely through earthquake activity and enhanced sediment supply. This study is a first step to evaluate the risk associated with submarine landslides in the region

Validation of Plasmodium falciparum dUTPase as the target of 5'-tritylated deoxyuridine analogues with anti-malarial activity

BACKGROUND: Malaria remains as a major global problem, being one of the infectious diseases that engender highest mortality across the world. Due to the appearance of resistance and the lack of an effective vaccine, the search of novel anti-malarials is required. Deoxyuridine 5'-triphosphate nucleotido-hydrolase (dUTPase) is responsible for the hydrolysis of dUTP to dUMP within the parasite and has been proposed as an essential step in pyrimidine metabolism by providing dUMP for thymidylate biosynthesis. In this work, efforts to validate dUTPase as a drug target in Plasmodium falciparum are reported. METHODS: To investigate the role of PfdUTPase in cell survival different strategies to generate knockout mutants were used. For validation of PfdUTPase as the intracellular target of four inhibitors of the enzyme, mutants overexpressing PfdUTPase and HsdUTPase were created and the IC50 for each cell line with each compound was determined. The effect of these compounds on dUTP and dTTP levels from P. falciparum was measured using a DNA polymerase assay. Detailed localization studies by indirect immunofluorescence microscopy and live cell imaging were also performed using a cell line overexpressing a Pfdut-GFP fusion protein. RESULTS:Different attempts of disruption of the dut gene of P. falciparum were unsuccessful while a 3' replacement construct could recombine correctly in the locus suggesting that the enzyme is essential. The four 5'-tritylated deoxyuridine analogues described are potent inhibitors of the P. falciparum dUTPase and exhibit antiplasmodial activity. Overexpression of the Plasmodium and human enzymes conferred resistance against selective compounds, providing chemical validation of the target and confirming that indeed dUTPase inhibition is involved in anti-malarial activity. In addition, incubation with these inhibitors was associated with a depletion of the dTTP pool corroborating the central role of dUTPase in dTTP synthesis. PfdUTPase is mainly localized in the cytosol. CONCLUSION: These results strongly confirm the pivotal and essential role of dUTPase in pyrimidine biosynthesis of P. falciparum intraerythrocytic stages

Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig

Analysis of TSG101 tumour susceptibility gene transcripts in cervical and endometrial cancers

Carcinoma of the uterine cervix is a common malignancy among women that has been found to show loss of heterozygosity in the chromosome 11p. Recent studies have localized the TSG101 gene in this region, and also demonstrated a high frequency of abnormalities of this gene in human breast cancer. To determine the role of the TSG101 gene in the carcinogenesis of cervical and uterine carcinoma, 19 cases of cervical carcinoma and five cases of endometrial carcinoma, as well as nearby non-cancerous tissue from the same patients, and 16 blood samples from healthy persons as normal control were analysed by Southern blot analysis of genomic DNA, reverse transcription of the TSG101 mRNA followed by PCR amplification and sequencing of the products. We found that abnormal transcripts of the TSG101 gene were common both in cancerous or non-cancerous tissues of the uterus and cervix and in normal peripheral mononuclear cells. There was no genomic deletion or rearrangement in spite of the presence of abnormal transcripts, and no definite relationship between the abnormal transcripts and HPV infection was found. Although the frequency of abnormal transcripts was higher in cancerous than in non-cancerous tissue, normal peripheral mononuclear cells also had abnormal transcripts. Given these findings, the role of the TSG101 gene as a tumour-suppressor gene should be re-evaluated. Because some aberrant transcripts could be found at the first PCR reaction, we suggest that the aberrant transcripts might be the result of imperfect minor splicesome products. © 1999 Cancer Research Campaig