Sedation for paediatric auditory electrophysiology in South Africa

Background: The sedation of children in the medical and allied professional fields has been a topic of controversy and debate internationally. Limited information is available on the use of sedation for auditory electrophysiology testing in South Africa.Objectives: The aim of this study was to determine how sedation information is recorded in electrophysiology audiology reports where diagnostic electrophysiology testing was used, and to obtain baseline information on sedation procedures and medications used during diagnostic electrophysiology testing.Methods: Audiology reports of 169 children undergoing auditory electrophysiology testing were reviewed for sedation information.Conclusion: Sedation data is not clearly documented and the use of medical or anaesthetist monitoring during sedation is not routinely included in reports. Sedation medication is varied and does not always include medications listed as safe for use with the paediatric population. This places doubt on procedures and protocols as well as the safety mechanisms in place for auditory diagnostic testing of children in South Africa.Keywords: auditory electrophysiology, diagnostic audiology, sedatio

The A-ring reduction of 11-ketotestosterone is efficiently catalysed by AKR1D1 and SRD5A2 but not SRD5A1

Testosterone and its 5α-reduced form, 5α-dihydrotestosterone, were previously thought to represent the only active androgens in humans. However, recent studies have shown that the potent androgen, 11-ketotestosterone, derived from the adrenal androgen precursor, 11β-hydroxyandrostenedione, may in fact serve as the primary androgen in healthy women. Yet, despite recent renewed interest in these steroids, their downstream metabolism has remained undetermined. We therefore set out to investigate the metabolism of 11-ketotestosterone by characterising the 5α- or 5β-reduction commitment step. We show that inactivation of 11-ketotestosterone is predominantly driven by AKR1D1, which efficiently catalyses the 5β-reduction of 11-ketotestosterone, committing it to a metabolic pathway that terminates in 11-ketoetiocholanolone. We demonstrate that 5α-reduction of 11-ketotestosterone is catalysed by SRD5A2, but not SRD5A1, and terminates in 11-ketoandrosterone, but is only responsible for a minority of 11-ketotestosterone inactivation. However, as 11-ketoetiocholanolone is also generated by the metabolism of the glucocorticoid cortisone, 11-ketoandrosterone should be considered a more specific urinary marker of 11-ketotestosterone production

Inhibition of the glucocorticoid‐activating enzyme 11β‐hydroxysteroid dehydrogenase type 1 drives concurrent 11‐oxygenated androgen excess

Aldo‐keto reductase 1C3 (AKR1C3) is a key enzyme in the activation of both classic and 11‐oxygenated androgens. In adipose tissue, AKR1C3 is co‐expressed with 11β‐hydroxysteroid dehydrogenase type 1 (HSD11B1), which catalyzes not only the local activation of glucocorticoids but also the inactivation of 11‐oxygenated androgens, and thus has the potential to counteract AKR1C3. Using a combination of in vitro assays and in silico modeling we show that HSD11B1 attenuates the biosynthesis of the potent 11‐oxygenated androgen, 11‐ketotestosterone (11KT), by AKR1C3. Employing ex vivo incubations of human female adipose tissue samples we show that inhibition of HSD11B1 results in the increased peripheral biosynthesis of 11KT. Moreover, circulating 11KT increased 2–3 fold in individuals with type 2 diabetes after receiving the selective oral HSD11B1 inhibitor AZD4017 for 35 days, thus confirming that HSD11B1 inhibition results in systemic increases in 11KT concentrations. Our findings show that HSD11B1 protects against excess 11KT production by adipose tissue, a finding of particular significance when considering the evidence for adverse metabolic effects of androgens in women. Therefore, when targeting glucocorticoid activation by HSD11B1 inhibitor treatment in women, the consequently increased generation of 11KT may offset beneficial effects of decreased glucocorticoid activation

FAK/src-Family Dependent Activation of the Ste20-Like Kinase SLK Is Required for Microtubule-Dependent Focal Adhesion Turnover and Cell Migration

Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal

On the reciprocal interaction between believing and feeling: an adaptive agent modelling perspective

An agent’s beliefs usually depend on informational or cognitive factors such as observation or received communication or reasoning, but also affective factors may play a role. In this paper, by adopting neurological theories on the role of emotions and feelings, an agent model is introduced incorporating the interaction between cognitive and affective factors in believing. The model describes how the strength of a belief may not only depend on information obtained, but also on the emotional responses on the belief. For feeling emotions a recursive body loop between preparations for emotional responses and feelings is assumed. The model introduces a second feedback loop for the interaction between feeling and belief. The strength of a belief and of the feeling both result from the converging dynamic pattern modelled by the combination of the two loops. For some specific cases it is described, for example, how for certain personal characteristics an optimistic world view is generated in the agent’s beliefs, or, for other characteristics, a pessimistic world view. Moreover, the paper shows how such affective effects on beliefs can emerge and become stronger over time due to experiences obtained. It is shown how based on Hebbian learning a connection from feeling to belief can develop. As these connections affect the strenghts of future beliefs, in this way an effect of judgment ‘by experience built up in the past’ or ‘by gut feeling’ can be obtained. Some example simulation results and a mathematical analysis of the equilibria are presented

Dissociable Effects of Valence and Arousal in Adaptive Executive Control

Background: Based on introspectionist, semantic, and psychophysiological experimental frameworks, it has long been assumed that all affective states derive from two independent basic dimensions, valence and arousal. However, until now, no study has investigated whether valence and arousal are also dissociable at the level of affect-related changes in cognitive processing.Methodology/Principal Findings: We examined how changes in both valence (negative vs. positive) and arousal (low vs. high) influence performance in tasks requiring executive control because recent research indicates that two dissociable cognitive components are involved in the regulation of task performance: amount of current control (i.e., strength of filtering goal-irrelevant signals) and control adaptation (i.e., strength of maintaining current goals over time). Using a visual pop-out distractor task, we found that control is exclusively modulated by arousal because interference by goal-irrelevant signals was largest in high arousal states, independently of valence. By contrast, control adaptation is exclusively modulated by valence because the increase in control after trials in which goal-irrelevant signals were present was largest in negative states, independent of arousal. A Monte Carlo simulation revealed that differential effects of two experimental factors on control and control adaptation can be dissociated if there is no correlation between empirical interference and conflict-driven modulation of interference, which was the case in the present data. Consequently, the observed effects of valence and arousal on adaptive executive control are indeed dissociable. Conclusions/Significance: These findings indicate that affective influences on cognitive processes can be driven by independent effects of variations in valence and arousal, which may resolve several heterogeneous findings observed in previous studies on affect-cognition interactions

Anger as “seeing red”: Evidence for a perceptual association

Metaphor representation theory contends that people conceptualise their non-perceptual states (e.g., emotion concepts) in perceptual terms. The present research extends this theory to colour manipulations and discrete emotional representations. Two experiments (N=265) examined whether a red font colour would facilitate anger conceptions, consistent with metaphors referring to anger to “seeing red”. Evidence for an implicit anger-red association was robust and emotionally discrete in nature. Further, Experiment 2 examined the directionality of such associations and found that they were asymmetrical: Anger categorisations were faster when a red font colour was involved, but redness categorisations were not faster when an anger-related word was involved. Implications for multiple literatures are discussed

Project management between will and representation

This article challenges some deep-rooted assumptions of project management. Inspired by the work of the German philosopher, Arthur Schopenhauer, it calls for looking at projects through two complementary lenses: one that accounts for cognitive and representational aspects and one that accounts for material and volitional aspects. Understanding the many ways in which these aspects transpire and interact in projects sheds new light on project organizations, as imperfect and fragile representations that chase a shifting nexus of intractable human, social, technical, and material processes. This, in turn, can bring about a new grasp of notions such as value,\ud knowledge, complexity, and risk

A creative destruction approach to replication: implicit work and sex morality across cultures

How can we maximize what is learned from a replication study? In the creative destruction approach to replication, the original hypothesis is compared not only to the null hypothesis, but also to predictions derived from multiple alternative theoretical accounts of the phenomenon. To this end, new populations and measures are included in the design in addition to the original ones, to help determine which theory best accounts for the results across multiple key outcomes and contexts. The present pre-registered empirical project compared the Implicit Puritanism account of intuitive work and sex morality to theories positing regional, religious, and social class differences; explicit rather than implicit cultural differences in values; self-expression vs. survival values as a key cultural fault line; the general moralization of work; and false positive effects. Contradicting Implicit Puritanism's core theoretical claim of a distinct American work morality, a number of targeted findings replicated across multiple comparison cultures, whereas several failed to replicate in all samples and were identified as likely false positives. No support emerged for theories predicting regional variability and specific individual-differences moderators (religious affiliation, religiosity, and education level). Overall, the results provide evidence that work is intuitively moralized across cultures