NMR Metabolomics Protocols for Drug Discovery

Drug discovery is an extremely difficult and challenging endeavor with a very high failure rate. The task of identifying a drug that is safe, selective and effective is a daunting proposition because disease biology is complex and highly variable across patients. Metabolomics enables the discovery of disease biomarkers, which provides insights into the molecular and metabolic basis of disease and may be used to assess treatment prognosis and outcome. In this regard, metabolomics has evolved to become an important component of the drug discovery process to resolve efficacy and toxicity issues, and as a tool for precision medicine. A detailed description of an experimental protocol is presented that outlines the application of NMR metabolomics to the drug discovery pipeline. This includes: (1) target identification by understanding the metabolic dysregulation in diseases, (2) predicting the mechanism of action of newly discovered or existing drug therapies, (3) and using metabolomics to screen a chemical lead to assess biological activity. Unlike other OMICS approaches, the metabolome is “fragile”, and may be negatively impacted by improper sample collection, storage and extraction procedures. Similarly, biologically-irrelevant conclusions may result from incorrect data collection, pre-processing or processing procedures, or the erroneous use of univariate and multivariate statistical methods. These critical concerns are also addressed in the protocol

Gender differentials in the presentation of symptoms, assessment, diagnosis and treatment of mentally ill prisoners

Critical criminologists have written extensively about the gendered nature of the criminal justice system and of its deleterious consequences. This chapter will continue in that same tradition and examine the extent to which gender plays a key role in the presentation of symptoms, assessment, diagnosis and treatment of mentally ill prisoners. The importance of such an exercise is clear. The 'Standard Minimum Rules for the Treatment of Prisoners' that was adopted by the First United Nations Congress on the Prevention of Crime and the Treatment of Offenders in 1955 made it very clear via Rule 62 that [t]he medical services of the institution shall seek to detect and shall treat any… mental illnesses or defects which may hamper a prisoner's rehabilitation'. Thus, the ensuing analysis here will explore how the gender of a prisoner influences the way in which a mentally ill inmate presents their symptoms (and seeks medical assistance); as well as, how they are thereafter assessed, diagnosed and treated by prison health services. By doing so, it is hoped that penal administrators and correctional health professionals in India will be made more aware of, or sensitive to, these variances, and that the subsequent assessment, diagnosis and treatment of such prisoners will be more gender-responsive so as to maximize the prospect of successful rehabilitation

Symbols of Resilience and Contested Place Identity in the Coastal Fishing Towns of Cromer and Sheringham, Norfolk, UK: Implications for Social Wellbeing

Fishing has been a core part of the identities of Cromer and Sheringham, rural coastal communities with a long tradition of inshore crab fishing in the East of England. However, given the decline in the number of fishing boats and wider demographic, economic and social change, the fishing identity of these towns is perceived as threatened. Drawing on qualitative research, this chapter develops a conceptual approach drawing on perspectives from place research and social wellbeing to explore the different place meanings held by coastal residents, visitors and fishermen. A focus on how different people relate to place and with each other provides a more nuanced understanding of social wellbeing. Tensions over place identity are exposed particularly between ‘newcomers’ and local residents, and over aspirations for economic development. Cromer and Sheringham’s fishing identity is being defended by the fishermen and those who value the fishery. This case study reveals the political nature of how different understandings of place, development and wellbeing are constructed and contested. The future of the fishery and the town will depend on whose values and place meanings are privileged and represented in governance processes