Wittgenstein and Derrida : ethics of the name

Similar tendencies in the work of philosophers Ludwig Wittgenstein and Jacques Derrida appear in their thoughts on language and lead to similarities in their respective ethical thought. Their views are such that the way in which they conceive the operation of meaning lead to a stance that rejects the possibility of total knowledge or command of concepts, and therefore refuses the idea of a "correct" account of meaning, morality, history, knowledge, and so on. This thesis is an attempt to identify and elaborate the overlap between Wittgenstein and Derrida's work in light of the role that proper names play in their philosophies of language and ethics. The philosophical account of proper names is important because it clarifies the view of subjectivity and also serves as a model for understanding the general operation of language. The fact that we are revealed to be inextricably dependent on the "otherness" of other people in order for each of us to be "selves" implies we are indebted to others and therefore must initiate any ethical project based on that indebtedness. Furthermore, the instability of language insures that we cannot have the "correct" interpretation of all concepts and must therefore maintain a certain charity in our dialogical engagement with others. This thesis argues in favour of the ethical stance that results from Wittgenstein and Derrida's perspective

SOURCES OF ERROR WHEN MEASURING ACHILLES TENDON MECHANICS DURING RUNNING ACTIVITIES

Accurate measurements of tendon mechanics are necessary for biomechanists when trying to identify injury risk factors, optimise athletic performance and develop musculoskeletal models. Measuring Achilles tendon (AT) mechanics dynamically is now possible by combining motion capture and ultrasound (US). The aim of this study was to quantify sources of error when measuring AT length using motion capture and US, and establish their effect on calculated strain values. Errors in AT insertion tracking and data synchronisation caused differences in AT length and moment arm of 5.3 ± 1.1 mm and 11.2 ± 0.9 mm, respectively; this decreased calculated AT peak strain from 11.6 ± 3.5% to 5.4 ± 2.5%. These differences could significantly impact a researcher‘s interpretation of the effects of footwear, technique, and specific kinematics on AT loading

SOFT TISSUE MOVEMENT IN THE LOWER LIMB DURING DROP JUMPS

Understanding loading on the human body and movement energetics is essential for researchers and practitioners to optimise training and investigate potential mechanisms of injury and adaptation. Recent work has suggested soft tissue movement relative to underlying bones during impact affects not only calculated loading but also metabolic cost. The aim of this study was to quantify the movement of the centre of mass of the soft tissues of the shank during high-impact, drop jump landings from 30 and 45 cm in healthy, adult males, and quantify the work done by these tissues. Soft tissue centre of mass moved by up to 0.038 m in the vertical direction (average: 0.021 m), and the soft tissues performed 2.9-3.5 J of work (4.1-6.4 J absolute work) during the landings. These results may hence have a significant effect on calculated joint torques and movement energetics

The plight of the sense-making ape

This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception

Rethinking irrigation modernisation: Realising multiple objectives through the integration of fisheries

Irrigation has been, and will remain, instrumental in addressing water security (Sustainable Development Goal (SDG) 6), food insecurity (SDG 2) and poverty (SDG 1) goals. However, the global context in which irrigation takes place is changing rapidly. A call for healthier and more sustainable food systems is placing new demands on how irrigation is developed and managed. Growing pressures from competing water uses in the domestic and industrial sectors, as well increasing environmental awareness, mean irrigation is increasingly called on to perform better, delivering acceptable returns on investment and simultaneously improving food security, rural livelihoods and nutrition, as well as supporting environmental conservation. Better integration of fisheries (including aquaculture) in irrigation planning, investment and management can contribute to the modernisation of irrigation and the achievement of the multiple objectives that it is called on to deliver. A framework illustrating how fisheries can be better integrated with irrigation, and how the two can complement each other across a range of scales, from scheme to catchment and, ultimately, national level, is presented

A pilot Internet "Value of Health" Panel: recruitment, participation and compliance

Objectives To pilot using a panel of members of the public to provide preference data via the Internet Methods A stratified random sample of members of the general public was recruited and familiarised with the standard gamble procedure using an Internet based tool. Health states were perdiodically presented in "sets" corresponding to different conditions, during the study. The following were described: Recruitment (proportion of people approached who were trained); Participation (a) the proportion of people trained who provided any preferences and (b) the proportion of panel members who contributed to each "set" of values; and Compliance (the proportion, per participant, of preference tasks which were completed). The influence of covariates on these outcomes was investigated using univariate and multivariate analyses. Results A panel of 112 people was recruited. 23% of those approached (n = 5,320) responded to the invitation, and 24% of respondents (n = 1,215) were willing to participate (net = 5.5%). However, eventual recruitment rates, following training, were low (2.1% of those approached). Recruitment from areas of high socioeconomic deprivation and among ethnic minority communities was low. Eighteen sets of health state descriptions were considered over 14 months. 74% of panel members carried out at least one valuation task. People from areas of higher socioeconomic deprivation and unmarried people were less likely to participate. An average of 41% of panel members expressed preferences on each set of descriptions. Compliance ranged from 3% to 100%. Conclusion It is feasible to establish a panel of members of the general public to express preferences on a wide range of health state descriptions using the Internet, although differential recruitment and attrition are important challenges. Particular attention to recruitment and retention in areas of high socioeconomic deprivation and among ethnic minority communities is necessary. Nevertheless, the panel approach to preference measurement using the Internet offers the potential to provide specific utility data in a responsive manner for use in economic evaluations and to address some of the outstanding methodological uncertainties in this field

Stakeholder cooperation to overcome challenges in orphan medicine development: The example of Duchenne muscular dystrophy

Duchenne muscular dystrophy is a rare, progressive, muscle-wasting disease leading to severe disability and premature death. Treatment is currently symptomatic, but several experimental therapies are in development. Implemented care standards, validated outcome measures correlating with clinical benefit, and comprehensive information about the natural history of the disease are essential for regulatory approval of any treatment. However, for Duchenne muscular dystrophy and other rare diseases, these requirements are not always in place when potential therapies enter the clinical trial phase. A cooperative effort of stakeholders in Duchenne muscular dystrophy-including representatives from patients' groups, academia, industry, and regulatory agencies-is aimed at addressing this shortfall by identifying strategies to overcome challenges, developing the tools needed, and collecting relevant data. An open and constructive dialogue among European stakeholders has positively affected development of treatments for Duchenne muscular dystrophy; this approach could serve as a paradigm for development of treatments for rare diseases in general

Antifungal benzo[b]thiophene 1,1-dioxide IMPDH inhibitors exhibit pan-assay interference (PAINS) profiles

Fungi cause serious life-threatening infections in immunocompromised individuals and current treatments are now complicated by toxicity issues and the emergence of drug resistant strains. Consequently, there is a need for development of new antifungal drugs. Inosine monophosphate dehydrogenase (IMPDH), a key component of the de novo purine biosynthetic pathway, is essential for growth and virulence of fungi and is a potential drug target. In this study, a high-throughput screen of 114,000 drug-like compounds against Cryptococcus neoformans IMPDH was performed. We identified three 3-((5-substituted)-1,3,4-oxadiazol-2-yl)thio benzo[b]thiophene 1,1-dioxides that inhibited Cryptococcus IMPDH and also possessed whole cell antifungal activity. Analogs were synthesized to explore the SAR of these hits. Modification of the fifth substituent on the 1,3,4-oxadiazole ring yielded compounds with nanomolar in vitro activity, but with associated cytotoxicity. In contrast, two analogs generated by substituting the 1,3,4-oxadiazole ring with imidazole and 1,2,4-triazole gave reduced IMPDH inhibition in vitro, but were not cytotoxic. During enzyme kinetic studies in the presence of DTT, nucleophilic attack of a free thiol occurred with the benzo[b]thiophene 1,1-dioxide. Two representative compounds with substitution at the 5 position of the 1,3,4-oxadiazole ring, showed mixed inhibition in the absence of DTT. Incubation of these compounds with Cryptococcus IMPDH followed by mass spectrometry analysis showed non-specific and covalent binding with IMPDH at multiple cysteine residues. These results support recent reports that the benzo[b]thiophene 1,1-dioxides moiety as PAINS (pan-assay interference compounds) contributor