Habituation to pain : a motivational-ethological perspective

Habituation to pain is mainly studied using external pain stimuli in healthy volunteers, often to identify the underlying brain mechanisms, or to investigate problems in habituation in specific forms of pain (eg, migraine). Although these studies provide insight, they do not address one pertinent question: Why do we habituate to pain? Pain is a warning signal that urges us to react. Habituation to pain may thus be dysfunctional: It could make us unresponsive in situations where sensitivity and swift response to bodily damage are essential. Early theories of habituation were well aware of this argument. Sokolov argued that responding to pain should not decrease, but rather increase with repeated exposure, a phenomenon he called “sensitization.” His position makes intuitive sense: Why would individuals respond less to pain that inherently signals bodily harm? In this topical review, we address this question from a motivational ethological perspective. First, we describe some core characteristics of habituation. Second, we discuss theories that explain how and when habituation occurs. Third, we introduce a motivational-ethological perspective on habituation and explain why habituation occurs. Finally, we discuss how a focus on habituation to pain introduces important methodological, theoretical, and clinical implications, otherwise overlooked

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns : impact of design optimisation

Purpose: There is a need for alternative analgosedatives such as dexmedetomidine in neonates. Given the ethical and practical difficulties, protocol design for clinical trials in neonates should be carefully considered before implementation. Our objective was to identify a protocol design suitable for subsequent evaluation of the dosing requirements for dexmedetomidine in mechanically ventilated neonates. Methods: A published paediatric pharmacokinetic model was used to derive the dosing regimen for dexmedetomidine in a first-in-neonate study. Optimality criteria were applied to optimise the blood sampling schedule. The impact of sampling schedule optimisation on model parameter estimation was assessed by simulation and re-estimation procedures for different simulation scenarios. The optimised schedule was then implemented in a neonatal pilot study. Results: Parameter estimates were more precise and similarly accurate in the optimised scenarios, as compared to empirical sampling (normalised root mean square error: 1673.1% vs. 13,229.4% and relative error: 46.4% vs. 9.1%). Most importantly, protocol deviations from the optimal design still allowed reasonable parameter estimation. Data analysis from the pilot group (n = 6) confirmed the adequacy of the optimised trial protocol. Dexmedetomidine pharmacokinetics in term neonates was scaled using allometry and maturation, but results showed a 20% higher clearance in this population compared to initial estimates obtained by extrapolation from a slightly older paediatric population. Clearance for a typical neonate, with a post-menstrual age (PMA) of 40 weeks and weight 3.4 kg, was 2.92 L/h. Extension of the study with 11 additional subjects showed a further increased clearance in pre-term subjects with lower PMA. Conclusions: The use of optimal design in conjunction with simulation scenarios improved the accuracy and precision of the estimates of the parameters of interest, taking into account protocol deviations, which are often unavoidable in this event-prone population

Linear stabitlity analysis of a supercritical loop

Paper presented at the 9th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Malta, 16-18 July, 2012.Because of their unique properties, supercritical fluids are becoming increasingly popular for industrial applications. These fluids behave liquid like at low temperatures and gas like at higher temperatures, with a smooth transition in between. This makes them very suited as a solvent for chemical extraction and separation processes. Another important use is as a power fluid. Modern fossil fuel fired power plants all operate using supercritical water, and on a smaller power scale they are considered for organic rankine cycles and refrigeration. As they heat up, the density of a supercritical fluid changes shows a very sharp drop for temperatures close to the critical point. This large density difference can be used as the driving force to circulate the fluid in a loop, rather than using a pump. This idea is similar to natural circulation boiling loops, but the density difference is larger. It adds a layer of inherent safety to a design, as active components such as pumps are no longer required; but also adds an additional complexity: flow instabilities. It is well known from natural circulation boiling systems, that these loops can become unstable under certain conditions (e.g. high power and low flow rate). In this study, a simple supercritical loop is studied to determine the neutral stability boundary. This is done through linear stability analysis: the set of one-dimensional governing equations is first linearised and then the eigenvalues are determined. These describe the response, indicating if it is stable or not. The results indicate that there is a clear unstable area, which can be linked to different types of instabilities.dc201

Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium

Background: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. Objectives: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. Methods: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). Results: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100 pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. Discussion and conclusion: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure

Thermo-hydraulic comparison of 10 PPi metal foam and louvered fins for low velocity applications

Paper presented at the 9th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Malta, 16-18 July, 2012.To maximize the effectiveness and thus minimize the airside resistance, a relatively new heat enhancing material, aluminium foam, is compared with the current state-of-the-art, louvered fins, in a wind tunnel experiment. The comparison between both heat exchangers is done based on a well-defined Performance Evaluation Criterion (PEC), taking heat transfer and pressure drop in account. Furthermore, as the studied heat exchangers are so-called ‘low-capacity’ units, a non-uniform temperature field downstream the heat exchanger is induced. Therefore an area-mean temperature reading has been developed, with the aid of an infra red camera. Finally, the contribution of the contact resistance to the overall thermal resistance of these pressed-fit heat exchangers is investigated.dc201

Influence of the geometry on the thermohydraulics of a compound heat exchanger consisting of louvered fins and delta winglets

Paper presented at the 9th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Malta, 16-18 July, 2012.Louvered fin heat exchangers with round tubes are frequently used in heating, ventilation, air conditioning and refrigeration applications. In this paper delta winglet vortex generators are punched out of the louver surface, resulting in a so called compound design. Three-dimensional numerical simulations were performed. The delta winglets serve to reduce the size of the tube wakes, which are zones of poor heat transfer. A screening analysis of the most important geometrical parameters showed that the delta winglet geometry highly contributes to the thermal and hydraulic performance at low Reynolds numbers, while at higher Reynolds numbers the performance is mainly determined by the louver geometry. The compound heat exchanger has a better thermal hydraulic performance than when the louvers or the delta winglets are applied separately. The performance of the compound design is also compared to louvered, slit and plain fin heat exchangers. This clearly shows its potential. Especially for low Reynolds applications, the compound heat exchanger can be made smaller in size and thus more economical in cost