Hyperacusis: major research questions

Background: Hyperacusis is a troublesome symptom that can have a marked negative impact on quality of life.Objectives: To identify major research questions in hyperacusis.Materials and methods: Review of gaps in knowledge regarding hyperacusis, and where opportunities may lie to address these.Results: Eight major research questions were identified as priorities for future research. These were: What is the prevalence of hyperacusis in adults and children? What are the risk factors associated with hyperacusis? What is the natural history of hyperacusis? How is ‘pain hyperacusis’ perceived? What mechanisms are involved in hyperacusis? What is the relationship between hyperacusis and tinnitus? Can a questionnaire be developed that accurately measures the impact of hyperacusis and can be used as a treatment outcome measure? What treatments, alone or in combination, are effective for hyperacusis?Conclusion: This clinical/researcher-led project identified major research questions in hyperacusis. A further development to identify patient-prioritized research will follow

Engaging leaders at two hierarchical levels in organizational health interventions: insights from the intervention team

Purpose: Although visible leader support is an essential ingredient for successful organizational health interventions, knowledge on how leaders at different hierarchical levels engage with interventions is underdeveloped. The purpose of this paper is to explore leader engagement by drawing from the experiences of the intervention team. Design/methodology/approach: Data from semi-structured interviews with the team responsible for implementing an organizational health intervention in two large UK organizations were used to examine how leaders at strategic (senior management) and operational (line managers) positions engaged with the intervention. Findings: Thematic analysis uncovered 6 themes and 16 sub-themes covering the leaders’ initial reactions to the intervention, barriers to leader engagement, ways in which the intervention team dealt with these barriers, factors facilitating and factors accelerating leader engagement, and differences in engagement between leadership levels. Research limitations/implications: This study can inform research into the conditions for optimizing leader engagement in organizational health interventions and beyond. Insights also emerged on the roles of leaders at different hierarchical levels and the value of perspective taking for intervention implementation. Practical implications: Recommendations for bolstering the engagement of leaders in interventions are offered, that apply to all leaders or separately to leaders at strategic or operational levels. Originality/value: The experiences of the intervention team who sought to engage leaders at different organizational levels to support the intervention are invaluable. Understanding how leader engagement can be maximized can better equip intervention teams for delivering successful interventions

Size and emotion or depth and emotion? Evidence, using Matryoshka (Russian) dolls, of children using physical depth as a proxy for emotional charge

Background: The size and emotion effect is the tendency for children to draw people and other objects with a positive emotional charge larger than those with a negative or neutral charge. Here we explored the novel idea that drawing size might be acting as a proxy for depth (proximity).Methods: Forty-two children (aged 3-11 years) chose, from 2 sets of Matryoshka (Russian) dolls, a doll to represent a person with positive, negative or neutral charge, which they placed in front of themselves on a sheet of A3 paper. Results: We found that the children used proximity and doll size, to indicate emotional charge. Conclusions: These findings are consistent with the notion that in drawings, children are using size as a proxy for physical closeness (proximity), as they attempt with varying success to put positive charged items closer to, or negative and neutral charge items further away from, themselves

The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice

5,6-dimethylxanthenone-4-acetic acid, a novel antivascular anticancer drug, has completed Phase I clinical trial. Its actions in mice include tumour necrosis factor induction, serotonin release, tumour blood flow inhibition, and the induction of tumour haemorrhagic necrosis and regression. We have used mice with a targeted disruption of the tumour necrosis factor receptor-1 gene as recipients for the colon 38 carcinoma to determine the role of tumour necrosis factor signalling in the action of 5,6-dimethylxanthenone-4-acetic acid. The pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid, as well as the degree of induced plasma and tissue tumour necrosis factor, were similar in tumour necrosis factor receptor-1−/− and wild-type mice. However, the maximum tolerated dose of 5,6-dimethylxanthenone-4-acetic acid was considerably higher in tumour necrosis factor receptor-1−/− mice (>100 mg kg−1) than in wild-type mice (27.5 mg kg−1). The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (25 mg kg−1) was strongly attenuated in tumour necrosis factor receptor-1−/− mice. However, the reduced toxicity in tumour necrosis factor receptor-1−/− mice allowed the demonstration that at a higher dose (50 mg kg−1), 5,6-dimethylxanthenone-4-acetic acid was curative and comparable in effect to that of a lower dose (25 mg kg−1) in wild-type mice. The 5,6-dimethylxanthenone-4-acetic acid -induced rise in plasma 5-hydroxyindoleacetic acid, used to reflect serotonin production in a vascular response, was larger in colon 38 tumour bearing than in non-tumour bearing tumour necrosis factor receptor-1−/− mice, but in each case the response was smaller than the corresponding response in wild-type mice. The results suggest an important role for tumour necrosis factor in mediating both the host toxicity and antitumour activity of 5,6-dimethylxanthenone-4-acetic acid, but also suggest that tumour necrosis factor can be replaced by other vasoactive factors in its antitumour action, an observation of relevance to current clinical studies