'Saying it without words': a qualitative study of oncology staff's experiences with speaking up about safety concerns.

OBJECTIVES To explore the experiences of oncology staff with communicating safety concerns and to examine situational factors and motivations surrounding the decision whether and how to speak up using semistructured interviews. SETTING 7 oncology departments of six hospitals in Switzerland. PARTICIPANTS Diverse sample of 32 experienced oncology healthcare professionals. RESULTS Nurses and doctors commonly experience situations which raise their concerns and require questioning, clarifying and correcting. Participants often used non-verbal communication to signal safety concerns. Speaking-up behaviour was strongly related to a clinical safety issue. Most episodes of 'silence' were connected to hygiene, isolation and invasive procedures. In contrast, there seemed to exist a strong culture to communicate questions, doubts and concerns relating to medication. Nearly all interviewees were concerned with 'how' to say it and in particular those of lower hierarchical status reflected on deliberate 'voicing tactics'. CONCLUSIONS Our results indicate a widely accepted culture to discuss any concerns relating to medication safety while other issues are more difficult to voice. Clinicians devote considerable efforts to evaluate the situation and sensitively decide whether and how to speak up. Our results can serve as a starting point to develop a shared understanding of risks and appropriate communication of safety concerns among staff in oncology.

Collective Referential Intentionality in the Semantics of Dialogue

The concept of a dialogue is considered in general terms from the standpoint of its referential presuppositions. The semantics of dialogue implies that dialogue participants must generally have a collective intentionality of agreed-upon references that is minimally sufficient for them to be able to disagree about other things, and ideally for outstanding disagreements to become clearer at successive stages of the dialogue. These points are detailed and illustrated in a fictional dialogue, in which precisely these kinds of referential confusions impede progress in shared understanding. It is only through a continuous exchange of question and answer in this dialogue case study that the meanings of key terms and anaphorical references are disambiguated, and a relevantly complete collective intentionality of shared meaning between dialogue participants is achieved. The importance of a minimally shared referential semantics for the terms entering into reasoning and argument in dialogue contexts broadly construed cannot be over-estimated. Where to draw the line between referential agreement and disagreement within any chosen dialogue, as participants work toward better mutual understanding in clearing up referential incongruities, is sometimes among the dialogue’s main points of dispute.

A comprehensive understanding of thioTEPA metabolism in the mouse using UPLC-ESI-QTOFMS-based metabolomics

ThioTEPA, an alkylating agent with anti-tumor activity, has been used as an effective anticancer drug since the 1950s. However, a complete understanding of how its alkylating activity relates to clinical efficacy has not been achieved, the total urinary excretion of thioTEPA and its metabolites is not resolved, and the mechanism of formation of the potentially toxic metabolites S-carboxymethylcysteine (SCMC) and thiodiglycolic acid (TDGA) remains unclear. In this study, the metabolism of thioTEPA in a mouse model was comprehensively investigated using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based-metabolomics. The nine metabolites identified in mouse urine suggest that thioTEPA underwent ring-opening, N-dechloroethylation, and conjugation reactions in vivo. SCMC and TDGA, two downstream thioTEPA metabolites, were produced from thioTEPA from two novel metabolites 1,2,3-trichloroTEPA (VII) and dechloroethyltrichloroTEPA (VIII). SCMC and TDGA excretion were increased about 4-fold and 2-fold, respectively, in urine following the thioTEPA treatment. The main mouse metabolites of thioTEPA in vivo were TEPA (II), monochloroTEPA (III) and thioTEPA-mercapturate (IV). In addition, five thioTEPA metabolites were detected in serum and all shared similar disposition. Although thioTEPA has a unique chemical structure which is not maintained in the majority of its metabolites, metabolomic analysis of its biotransformation greatly contributed to the investigation of thioTEPA metabolism in vivo, and provides useful information to understand comprehensively the pharmacological activity and potential toxicity of thioTEPA in the clinic.

Approaching diplomatic and courtly gift-giving in Europe and Mughal India. Shared practices and cultural diversity

This article deals with courtly gift-giving practices in Europe and Mughal India from a comparative and interwoven perspective. Given the historiographical lacunae on Mughal gift-giving, the article presents preliminary observations for further research. Unlike most contributions to this volume, this article understands the notion of diversity in terms of an intercultural diversity that came to the fore in courtly contexts and in diplomatic encounters. My arguments are bifold. On the one hand, European and Mughal rulers and their envoys shared a common ground of diplomatic gift-giving practices that were shaped by an understanding of what was worthy of giving and of the symbolic power of the given objects. On the other hand, courtly gift-giving practices were embedded in different social and cultural environments in Europe and India. By looking at the notion of the ‘gift’ and the social organisation of the Mughal elite, it becomes clear that pīshkash was an idiosyncratic concept in South and Central Asian contexts and that offerings of manṣabdārs to the Mughal emperor had a different character than those of European courtiers to their rulers.

A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12.

Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds-the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10-11). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018-5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.