prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis

Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis during primary infection is unknown. To investigate this question, we characterized the functional properties of newly-generated dengue virus (DENV) prM-reactive monoclonal antibodies (mAbs) in vitro and using a mouse model of DENV disease. Anti-prM mAbs neutralized DENV infection in a virion maturation state-dependent manner. Alanine scanning mutagenesis and cryoelectron microscopy of anti-prM mAbs in complex with immature DENV defined two modes of attachment to a single antigenic site. In vivo, passive transfer of intact anti-prM mAbs resulted in an antibody-dependent enhancement of disease. However, protection against DENV-induced lethality was observed when the transferred mAbs were genetically modified to inhibit their ability to interact with Fcγ receptors. These data establish that in addition to mature forms of the virus, partially mature infectious pr

From absent to present pasts: civil society, democracy and the shifting place of memory in Brazil

This paper takes Alexis de Tocqueville’s concern with the emotional life of citizens as a cue for exploring the role of collective memory within ‘the self-organizing sphere’ and asking how the invocation of memory affects progress towards democracy. The paper hones in on the Brazilian experience, re-assessing Brazil’s amnesiac past as well as its much lauded ‘turn to memory’. Against common assertions that Brazil’s ‘turn to memory’ will enhance the country’s democratic credentials, this paper argues that the move from an ‘absent’ to a ‘present’ past in Brazil in fact bodes rather mixed prospects for the country’s democratic deepening

A broadly reactive antibody targeting the N-terminal domain of SARS-CoV-2 spike confers Fc-mediated protection

Most neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) target the receptor binding domain (RBD) of the spike (S) protein. Here, we characterize a panel of mAbs targeting the N-terminal domain (NTD) or other non-RBD epitopes of S. A subset of NTD mAbs inhibits SARS-CoV-2 entry at a post-attachment step and avidly binds the surface of infected cells. One neutralizing NTD mAb, SARS2-57, protects K18-hACE2 mice against SARS-CoV-2 infection in an Fc-dependent manner. Structural analysis demonstrates that SARS2-57 engages an antigenic supersite that is remodeled by deletions common to emerging variants. In neutralization escape studies with SARS2-57, this NTD site accumulates mutations, including a similar deletion, but the addition of an anti-RBD mAb prevents such escape. Thus, our study highlights a common strategy of immune evasion by SARS-CoV-2 variants and how targeting spatially distinct epitopes, including those in the NTD, may limit such escape

The production of trust during organizational change

This paper investigates the relationships between organizational change and trust in management. It is argued that organizational change represents a critical episode for the production and destruction of trust in management. Although trust in management is seen as a semi stable psychological state, changes in organizations make trust issues salient and organizational members attend to and process trust relevant information resulting in a reassessment of their trust in management. The direction and magnitude of change in trust is dependent on a set of change dimensions that reflect trust relevant experiences and information. We distinguish between dimensions related to trust relevant consequences of the change and trust relevant aspects of how the change process is performed. Empirical results indicate that increases in post change emotional stress and the use of referential accounts for justifying change are both negatively related to post change trust in management. The use of ideological accounts and participation were found to be positively related to post change trust in management, so was perceived decision quality. Findings also indicate that the effects of change on trust are negatively moderated by tenure

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

Job insecurity, employee anxiety, and commitment: The moderating role of collective trust in management

This article examines the moderating effect of collective trust in management on the relation between job insecurity (both objective and subjective) and employee outcomes (work-related anxiety and organisational commitment). This is contextualised in the modern British workplace which has seen increased employment insecurity and widespread cynicism. We use matched employer-employee data extracted from the British Workplace Employment Relations Survey (WERS) 2011, which includes over 16,000 employees from more than 1100 organisations. The multilevel analyses confirm that objective job insecurity (loss of important elements of a job such as cuts in pay, overtime, training, and working hours) are significantly correlated with high levels of work-related anxiety and lower levels of organisational commitment. These correlations are partially mediated by subjective job insecurity (perception of possible job loss). More importantly, collective trust in management (a consensus of management being reliable, honest and fair) significantly attenuates the negative impact of objective job insecurity on organisational commitment, and reduces the impact of subjective job insecurity on work-related anxiety. Theoretical and practical implications and limitations of these effects are discussed

Understanding the factors that determine workplace coaching effectiveness: a systematic literature review

Meta-analytic results have established that workplace coaching is effective, however, little is known about the determinants of coaching effectiveness. This paper reports an inclusive systematic literature review, covering the quantitative and qualitative research on workplace coaching. We focus on seven promising areas in the current workplace coaching literature that emerged by the synthesis of 117 empirical studies: self-efficacy, coaching motivation, goal orientation, trust, interpersonal attraction, feedback intervention, and supervisory support. The major contribution of our paper is the systematic integration of well-established theoretical constructs in the workplace coaching context and the new insights we provide in the synthesis of these literatures. Based on our review we provide specific recommendations to be addressed in future research, including recommended research methodologies, which we propose will significantly progress the field of workplace coaching theory and practice

High Involvement Management, High Performance Work Systems and Well-being

Studies on the impact of high-performance work systems on employees' well-being are emerging but the underlying theory remains weak. This paper attempts to develop theory of the effects on well-being of four dimensions of high-performance work systems: enriched jobs, high involvement management, employee voice, and motivational supports. Hypothesized associations are tested using multilevel models and data from Britain's Workplace Employment Relations Survey of 2004 (WERS2004). Results show that enriched jobs are positively associated with both measures of well-being: job satisfaction and anxiety–contentment. Voice is positively associated with job satisfaction, and motivational supports with neither measure. The results for high involvement management are not as predicted because it increases anxiety and is independent of job satisfaction

A realist evaluation of the management of a well- performing regional hospital in Ghana

<p>Abstract</p> <p>Background</p> <p>Realist evaluation offers an interesting approach to evaluation of interventions in complex settings, but has been little applied in health care. We report on a realist case study of a well performing hospital in Ghana and show how such a realist evaluation design can help to overcome the limited external validity of a traditional case study.</p> <p>Methods</p> <p>We developed a realist evaluation framework for hypothesis formulation, data collection, data analysis and synthesis of the findings. Focusing on the role of human resource management in hospital performance, we formulated our hypothesis around the high commitment management concept. Mixed methods were used in data collection, including individual and group interviews, observations and document reviews.</p> <p>Results</p> <p>We found that the human resource management approach (the actual intervention) included induction of new staff, training and personal development, good communication and information sharing, and decentralised decision-making. We identified 3 additional practices: ensuring optimal physical working conditions, access to top managers and managers' involvement on the work floor. Teamwork, recognition and trust emerged as key elements of the organisational climate. Interviewees reported high levels of organisational commitment. The analysis unearthed perceived organisational support and reciprocity as underlying mechanisms that link the management practices with commitment.</p> <p>Methodologically, we found that realist evaluation can be fruitfully used to develop detailed case studies that analyse how management interventions work and in which conditions. Analysing the links between intervention, mechanism and outcome increases the explaining power, while identification of essential context elements improves the usefulness of the findings for decision-makers in other settings (external validity). We also identified a number of practical difficulties and priorities for further methodological development.</p> <p>Conclusion</p> <p>This case suggests that a well-balanced HRM bundle can stimulate organisational commitment of health workers. Such practices can be implemented even with narrow decision spaces. Realist evaluation provides an appropriate approach to increase the usefulness of case studies to managers and policymakers.</p