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

Uptake and localisation of mTHPC (Foscan®) and its14C-labelled form in normal and tumour tissues of the hamster squamous cell carcinoma model: a comparative study

The aim of this study was to evaluate the pharmacokinetics of meta(tetrahydroxyphenyl)chlorin (mTHPC) on different tissues of interest in a hamster tumour model and to confirm our earlier animal studies on semi-quantitative fluorescence microscopy. The results obtained by three different evaluation methods were compared: in vivo spectrofluorometry, ex vivo fluorescence microscopy and chemical extraction of 14C-labelled mTHPC. Following intracardiac injection of 0.5 mg kg−1 mTHPC, groups of five tumour-bearing animals were used for in situ light-induced fluorescence spectroscopy. Afterwards, the biopsies were taken and snap frozen for fluorescence microscopy. The presence of radioactivity in serum and tissues was determined after chemical digestion in scintillation fluid using a scintillation counter. For each analysed tissue, a good correlation was observed between the three evaluation methods. The highest fluorescence intensity and quantities of mTHPC were observed between 12 and 24 h in liver, kidney, serum, vascular endothelium and advanced neoplasia. The majority of mTHPC was found at around 48 h in smooth muscle and at 96 h in healthy cheek pouch mucosa and early malignant lesions. The lowest level of mTHPC was noted in striated muscle at all times. No selectivity in dye localisation was observed between early squamous cell carcinoma and healthy mucosa. Soon after the injection, a significant selectivity was noted for advanced squamous cell carcinoma as compared to healthy cheek pouch mucosa or striated muscle. A significant difference in mTHPC localisation and quantity was also observed between striated and smooth muscle during the first 48 h following the injection. Finally, this study demonstrated the usefulness of non-invasive in situ spectroscopic measurements to be performed systematically prior to photodynamic therapy as a real-time monitoring for each treated patient in order to individualise and adapt the light dosimetry and avoid over or under treatments

Tempo and the TFR

Tempo effects in period fertility indicators are widely regarded as a source of bias or distortion. But is this always the case? Whether tempo change results in bias depends, in the view advanced here, on the measure used, the meaning of bias/distortion, and the objective of analysis. Two ways of construing bias in period measures are suggested, and their relevance is discussed in the context of five broad purposes for measuring period fertility: describing and explaining fertility time trends, anticipating future prospects, providing input parameters for formal models, and communicating with nonspecialist audiences. Genuine timing effects are not biasing when period fertility is the explanandum but are distorting when the aim is to estimate cohort fertility. Alternatives to tempo adjustment are available that are a more defensible solution to the issue of timing change. Tempo adjustment could be more fruitfully considered a form of modeling rather than empirical measurement. The measurement of period fertility could be improved by relying more on a statistical approach and less on indicators based on stable assumptions. Future progress will depend on integrating research on measurement with substantive investigation

The Politics of Institutional Reform and Post-Conflict Violence in Nepal

How does the reform of state institutions shape prospects for peace after war? Existing research on the institutional causes of peace focuses on how institutional designs, as the outcomes of reform processes, reduce post-conflict violence and promote peace. The literature does not, however, adequately address how the politics that characterise reform processes affect the legitimacy of institutions and whether or not violent protest against these institutions ultimately takes place. This focus risks omitting key explanations of how institutional reforms contribute to peace and the mechanisms by which this occurs. By examining the case of Nepal, where clashes between protesters and security forces killed almost 60 people between August 2015 and January 2016, this study shows that emotional rhetoric, elite control of decision-making, backtracking on previous commitments, the acceleration of reform processes, and the embedding of single reforms in a 'concert' of reforms that, as a whole, sparks fears of discrimination are all factors that can lead to post-conflict violence

The syntax and semantics of infinitives of result in English

This thesis concerns infinitives of result in English, examples of which are given under (a-c). (a) John designed a battery to operate at high temperatures. (b) John designed a battery to win a prize. (c) John designed a battery for the competition, only to discover that he was ineligible. The infinitive in (a) is called a Purpose Clause; the infinitive in (b) is called a Rationale Clause; and the infinitive in (c) is called a Telic Clause. These infinitives are optional modifiers of the verbs with which they occur. I argue, however, that important characteristics of their form and interpretation follow naturally if the infinitives are assumed to have argument structures which must be incorporated into the argument structure of the verb they modify. In Chapter 1, I introduce the constructions and offer a general discussion of the problems posed by modifiers in a study of natural language semantics, arguing that these problems are best addressed by viewing modifiers as predicates of a standard sort. This establishes a central hypothesis of this thesis, namely that the syntax and semantics of modification should be incorporated into the theory of argument structure, or "theta theory". In Chapter 2, I offer a summary of key works in the literature in two areas: theories of argument projection by Williams and Higginbotham and studies of infinitives of result by Faraci, Bach, Chierchia, and Jones. In Chapter 3, I apply a range of syntactic tests to establish the structural relation of the infinitives to the sentences they modify. I argue that the infinitives are embedded at an increasing distance from the modified verb, from which important characteristics of their distribution follow. In Chapter 4, I turn to the internal syntax of the constructions and consider the nature and distribution of the gaps that occur within each infinitive and the manner in which those gaps are interpreted. I relate key characteristics of the infinitives to the nature of their argument grids. I also address constraints on interpretation introduced by pronominal binding in the infinitives. In Chapter 5, I discuss a variety of problems on the syntax-semantics interface involving argument structure and control. The issues raised move from the relatively syntactic (phrase structure accounts of Purpose Clause antecedence and the possibility of event control for the Rationale and Telic Clauses) to the philosophical semantic (causal efficacy and the nature of resultant states in the interpretation of the Purpose Clause). I then offer a full sample analysis of a sentence modified by all three infinitives of result. My conclusion points again to the importance of argument structure in an analysis of infinitives of result in particular and of modification in general.</p

Nationalism and Ethnicity in Nepal

Gellner D, Pfaff-Czarnecka J, Whelpton J, eds. Nationalism and Ethnicity in Nepal. Kathmandu: Vajra Publ.; 2008