Fluorobenzoyl dipeptidyl derivatives as inhibitors of the Fasciola hepatica cysteine protease cathepsin L1

Cathepsins are known to have many important physiological roles and provide a viable target for inhibition. Fluorobenzoyl dipeptide derivatives were synthesized and tested for biological activity in an effort to find an efficient inhibitor of the cysteine protease cathepsin L. Thirty-six novel inhibitors (1-36) were synthesized from protected amino acids via the standard DCC/HOBt coupling protocol, containing a benzyl ester or a nitrile as an electrophilic warhead. The activity of the inhibitors was evaluated against cathepsin L and IC50 values calculated. Modification of both amino acids and terminal groups afforded compounds with single digit micromolar inhibition. Results utilizing the benzoyl-L-leucine-glycine nitrile backbone are comparable to that for the commercially available inhibitor 39.

Psychosocial factors in GP work:the effects of taking a GP position or leaving GP work

BACKGROUND: We examined the effects of leaving public sector general practitioner (GP) work and of taking a GP position on changes in work-related psychosocial factors, such as time pressure, patient-related stress, distress and work interference with family. In addition, we examined whether changes in time pressure and patient-related stress mediated the association of employment change with changes of distress and work interference with family. METHODS: Participants were 1705 Finnish physicians (60% women) who responded to surveys in 2006 and 2010. Analyses of covariance were conducted to examine the effect of employment change to outcome changes adjusted for gender, age and response format. Mediational effects were tested following the procedures outlined by Baron and Kenny. RESULTS: Employment change was significantly associated with all the outcomes. Leaving public sector GP work was associated with substantially decreased time pressure, patient-related stress, distress and work interference with family. In contrast, taking a position as a public sector GP was associated with an increase in these factors. Mediation tests suggested that the associations of employment change with distress change and work interference with family change were partially explained by the changes in time pressure and patient-related stress. CONCLUSIONS: Our results showed that leaving public sector GP work is associated with favourable outcomes, whereas taking a GP position in the public sector is associated with adverse effects. Primary health-care organizations should pay more attention to the working conditions of their GPs, in particular, to time pressure and patient-related stress.

The mechanical effect of the existing cement mantle on the in-cement femoral revision

Cement-in-cement revision hip arthroplasty is an increasingly popular technique to replace a loose femoral stem which retains much of the original cement mantle. However, some concern exists regarding the retention of the existing fatigued and aged cement in such cement-in-cement revisions. This study investigates whether leaving an existing fatigued and aged cement mantle degrades the mechanical performance of a cement-in-cement revision construct.

Affective disruption: Walter Benjamin and the 'history' of Ireland's industrial schools

What role do organizations play in writing history? In this paper, I address the part played by organizations in the enactment of large-scale violence, and focus on the ways in which the resulting histories come to be written. Drawing on the case of Ireland's industrial schools, I demonstrate how such accounts can act to serve the interests of those in power, effectively silencing and marginalizing weaker people. A theoretical lens that draws on ideas from Walter Benjamin and Judith Butler is helpful in understanding this; the concept of 'affective disruption' enables an exploration of how people's experiences of organizational violence can be reclaimed from the past, and protected in a continuous remembrance. Overall, this paper contributes a new perspective on the writing of organizational histories, particularly in relation to the enactment of violence. 

Dangerously empty? Hegemony and the construction of the Irish entrepreneur

In this article we build on Jones and Spicer's (2009) conceptualization of the entrepreneur as an empty signifier. We explore the function of the signifier 'entrepreneurship' within a social context marked by crisis: Ireland 2007-2010. In doing so, we show how its articulation by government acted to legitimize the continuation of market logics and, relatedly, the existing political status quo. Theoretically, we demonstrate the usefulness of Laclau and Mouffe's conception of hegemony, which shares a Lacanian legacy with Jones and Spicer. This helps us to understand the contradictory nature of the signifier of the entrepreneur in Irish political and social discourse, along with its relationship to the reproduction of political hegemony.

'Someone Big and Important': Identification and Affect in an International Development Organization

Psychoanalysis has been widely used to develop our understanding of power in organizations. In this paper, I draw on a case study of a non-profit organization in the field of international development, in order to explore in depth how people engage with powerful discourses at play in this context. I use an ethnographic approach to do so, and find Lacan's ideas on identification and affect to be useful in the analysis of the case. I show how, at first glance, people appeared to readily alter their activities and goals in response to the wishes of an important donor. However, moving deeper to examine identifications on the part of people themselves reveals complex forms of recognition that were inscribed by affective relations. I discuss the implications of these findings for the study of organizations, including the contribution of the concept of affect for studies of identification and subjection in organizations, and the value of ethnographic research approaches that draw upon Lacan's work on recognition.