Reference values of mechanical and thermal pain tests in a pain-free population

Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain-free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.

Fuzzy Web Knowledge Aggregation, Representation, and Reasoning for Online Privacy and Reputation Management

A social Semantic Web empowers its users to have access to collective Web knowledge in a simple manner, and for that reason, controlling online privacy and reputation becomes increasingly important, and must be taken seriously. This chapter presents Fuzzy Cognitive Maps (FCM) as a vehicle for Web knowledge aggregation, representation, and reasoning. With this in mind, a conceptual framework for Web knowledge aggregation, representation, and reasoning is introduced along with a use case, in which the importance of investigative searching for online privacy and reputation is highlighted. Thereby it is demonstrated how a user can establish a positive online presence.

Managing Knowledge Transfer in Software-Maintenance Outsourcing Transitions: A System-Dynamics Perspective

The existing literature suggests that transitions in software-maintenance offshore outsourcing projects are prone to knowledge transfer blockades, i.e. situations in which the activities that would yield effective knowledge transfer do not occur, and that client management involvement is central to overcome them. However, the theoretical understanding of the knowledge transfer blockade is limited, and the reactive management behavior reported in case studies suggests that practitioners may frequently be astonished by the dynamics that may give rise to the blockade. Drawing on recent research from offshore sourcing and reference theories, this study proposes a system dynamics framework that may explain why knowledge transfer blockades emerge and how and why client management can overcome the blockade. The results suggest that blockades may emerge from a vicious circle of weak learning due to cognitive overload of vendor staff and resulting negative ability attributions that result in reduced helping behavior and thus aggravate cognitive load. Client management may avoid these vicious circles by selecting vendor staff with strong prior related experience. Longer phases of coexistence of vendor staff and subject matter experts and high formal and clan controls may also mitigate vicious circles.

LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases

BACKGROUND Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking. METHODS We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification. To assess reference intervals and intra-individual variation we determined oxysterols in 148 children and adolescents from 0 to 18 years and repeat measurements in 19 of them. RESULTS The reported method is linear (r>0.99), sensitive (detection limit of 0.03 ng/mL [0.07 nM] for C-triol, and 0.54 ng/mL [1.35 nM] for 7-KC) and precise, with an intra-day imprecision of 4.8% and 4.1%, and an inter-day imprecision of 7.0% and 11.0% for C-triol (28 ng/ml, 67 nM) and 7-KC (32 ng/ml, 80 nM), respectively. Recoveries for 7-KC and C-triol range between 93% and 107%. The upper reference limit obtained for C-triol is 40.4 ng/mL (95% CI: 26.4-61.7 ng/mL, 96.0 nM, 95% CI: 62.8-146.7 nM) and 75.0 ng/mL for 7-KC (95% CI: 55.5-102.5 ng/mL, 187.2 nM, 95% CI: 138.53-255.8 nM), with no age or gender dependency. Both oxysterols have a broad intra-individual variation of 46%±23% for C-triol and 52%±29% for 7-KC. Nevertheless, all Niemann-Pick patients showed increased C-triol levels including Niemann-Pick type A and B patients. CONCLUSIONS The LC-MS/MS assay is a robust assay to quantify C-triol and 7-KC in plasma with well documented reference intervals in children and adolescents to screen for NP-C in the pediatric population. In addition our results suggest that especially the C-triol is a biomarker for all three Niemann-Pick diseases.