Expression and analysis of the glycosylation properties of recombinant human erythropoietin expressed in Pichia pastoris

The Pichia pastoris expression system was used to produce recombinant human erythropoietin, a protein synthesized by the adult kidney and responsible for the regulation of red blood cell production. The entire recombinant human erythropoietin (rhEPO) gene was constructed using the Splicing by Overlap Extension by PCR (SOE-PCR) technique, cloned and expressed through the secretory pathway of the Pichia expression system. Recombinant erythropoietin was successfully expressed in P. pastoris. The estimated molecular mass of the expressed protein ranged from 32 kDa to 75 kDa, with the variation in size being attributed to the presence of rhEPO glycosylation analogs. A crude functional analysis of the soluble proteins showed that all of the forms were active in vivo

OVERHEATED SECURITY? The Securitisation of Climate Change and the Governmentalisation of Security

Since the mid-2000s, climate change has become one of the defining security issues in political as well as academic debates and amongst others has repeatedly been discussed in the UN Security Council and countless high level government reports in various countries. Beyond the question whether the characterisation as ‘security issue’ is backed up by any robust empirical findings, this begs the question whether the ‘securitisation’ of climate change itself has had tangible political consequences. Moreover, within this research area there is still a lively discussion about which security conceptions apply, how to conceptualise (successful) securitisation and whether it is a (politically and normatively) desirable approach to deal with climate change. The aim of this dissertation is to shed light on these issues and particularly to contribute to a more thorough understanding of different forms or ‘discourses’ of securitisation and their political effects on a theoretical and empirical level. Theoretically, it conceptualises securitisation as resting on different forms of power, which are derived from Michel Foucault’s governmentality lectures. The main argument is that this framework allows me to better capture the ambiguous and diverse variants of securitisation and the ever-changing concept of security as well as to come to a more thorough understanding of the political consequences and powerful effects of constructing issues in terms of security. Empirically, the thesis looks at three country cases, namely the United States, Germany and Mexico. This comparative angle allows me to go beyond the existing literature on the securitisation of climate change that mostly looks at the global level, and to come to a more comprehensive and detailed understanding of different climate security discourses and their political consequences. Concerning the main results, the thesis finds that climate change has indeed been securitised very differently in the three countries and thus has facilitated diverse political consequences. These range from an incorporation of climate change into the defence sector in the US, the legitimisation of far-reaching climate policies in Germany, to the integration of climate change into several civil protection and agricultural insurance schemes in Mexico. Moreover, resting on different forms of power, the securitisation of climate change has played a key role in constructing specific actors and forms of knowledge as legitimate as well as in shaping certain identities in the face of the dangers of climate change. From a normative perspective, neither of these political consequences is purely good or bad but highly ambiguous and necessitates a careful, contextual assessment

Efficacy and Tolerability of High- vs Low-Volume Split-Dose Bowel Cleansing Regimens for Colonoscopy: A Systematic Review and Meta-analysis

Background & Aims Efficacy of bowel preparation is an important determinant of outcomes of colonoscopy. It is not clear whether approved low-volume polyethylene glycol (PEG) and non-PEG regimens are as effective as high-volume PEG regimens when taken in a split dose. Methods In a systematic review of multiple electronic databases through January 31, 2019 with a registered protocol (PROSPERO: CRD42019128067), we identified randomized controlled trials that compared low- vs high-volume bowel cleansing regimens, administered in a split dose, for colonoscopy. The primary efficacy outcome was rate of adequate bowel cleansing, and the secondary efficacy outcome was adenoma detection rate. Primary tolerability outcomes were compliance, tolerability, and willingness to repeat. We calculated relative risk (RR) and 95% CI values and assessed heterogeneity among studies by using the I2 statistic. The overall quality of evidence was assessed using the GRADE framework. Results In an analysis of data from 17 randomized controlled trials, comprising 7528 patients, we found no significant differences in adequacy of bowel cleansing between the low- vs high-volume split-dose regimens (86.1% vs 87.4%; RR, 1.00; 95% CI, 0.98–1.02) and there was minimal heterogeneity (I2 = 17%). There was no significant difference in adenoma detection rate (RR, 0.96; 95% CI, 0.87–1.08) among 4 randomized controlled trials. Compared with high-volume, split-dose regimens, low-volume split-dose regimens had higher odds for compliance or completion (RR, 1.06; 95% CI, 1.02–1.10), tolerability (RR, 1.39; 95% CI, 1.12–1.74), and willingness to repeat bowel preparation (RR, 1.41; 95% CI, 1.20–1.66). The overall quality of evidence was moderate. Conclusions Based on a systematic review of 17 randomized controlled trials, low-volume, split-dose regimens appear to be as effective as high-volume, split-dose regimens in bowel cleansing and are better tolerated, with superior compliance

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland

Background - Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. Methods - A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55–74 years, and (c) biennial faecal immunochemical tests (FIT) at 55–74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55–64 years) and staggered age-based roll-out across the 55–74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55–74). Results - FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381–1,053 with FSIG-based, and 967–1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. Conclusions - While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning