Intra- and inter-individual variation of BIS-index and Entropy during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

INTRODUCTION: We studied intra-individual and inter-individual variability of two online sedation monitors, BIS and Entropy, in volunteers under sedation. METHODS: Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS and Entropy (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered. RESULTS: Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy values showed greater variability than BIS(R) values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation. CONCLUSIONS: The large intra-individual and inter-individual variability of BIS and Entropy values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability. TRIAL REGISTRATION: clinicaltrials.gov Nr. NCT00641563.

Image quality of supine chest radiographs: intra-individual comparison of computed radiography and low-dose linear-slit digital radiography

The purpose of this retrospective study was to intra-individually compare the image quality of computed radiography (CR) and low-dose linear-slit digital radiography (LSDR) for supine chest radiographs. A total of 90 patients (28 female, 62 male; mean age, 55.1 years) imaged with CR and LSDR within a mean time interval of 2.8 days +/- 3.0 were included in this study. Two independent readers evaluated the image quality of CR and LSDR based on modified European Guidelines for Quality Criteria for chest X-ray. The Wilcoxon test was used to analyse differences between the techniques. The overall image quality of LSDR was significantly better than the quality of CR (9.75 vs 8.16 of a maximum score of 10; p < 0.001). LSDR performed significantly better than CR for delineation of anatomical structures in the mediastinum and the retrocardiac lung (p < 0.001). CR was superior to LSDR for visually sharp delineation of the lung vessels and the thin linear structures in the lungs. We conclude that LSDR yields better image quality and may be more suitable for excluding significant pathological features of the chest in areas with high attenuation compared with CR.

Mapping Individual Variation in Male Mating Preference Space: Multiple Choice in a Color Polymorphic Cichlid Fish

Sexual selection theory largely rests on the assumption that populations contain individual variation in mating preferences and that individuals are consistent in their preferences. However, there are few empirical studies of within-population variation and even fewer have examined individual male mating preferences. Here, we studied a color polymorphic population of the Lake Victoria cichlid fish Neochromis omnicaeruleus, a species in which color morphs are associated with different sex-determining factors. Wild-caught males were tested in three-way choice trials with multiple combinations of different females belonging to the three color morphs. Compositional log-ratio techniques were applied to analyze individual male mating preferences. Large individual variation in consistency, strength, and direction of male mating preferences for female color morphs was found and hierarchical clustering of the compositional data revealed the presence of four distinct preference groups corresponding to the three color morphs in addition to a no-preference class. Consistency of individual male mating preferences was higher in males with strongest preferences. We discuss the implications of these findings for our understanding of the mechanisms underlying polymorphism in mating preferences.

Illegitimate tasks associated with higher cortisol levels among male employees when subjective health is relatively low: an intra-individual analysis

Objectives Illegitimate tasks refer to tasks that do not conform to what can appropriately be expected from an employee. Violating role expectations, they constitute “identity-stressors”, as one’s professional role tends to become part of one’s identity. The current study investigated the impact of illegitimate tasks on salivary cortisol. We analyzed data on an intra-individual level, that is, by examining fluctuations in illegitimate tasks and cortisol within individuals. Furthermore, we investigated the moderating role of perceived health, expecting that illegitimate tasks evoke stronger reactions when perceived health is relatively poor. Methods Illegitimate tasks, salivary cortisol, and perceived health were assessed in each of three waves (time lag: 6 months) in a sample of 104 male employees. Data were analyzed by multilevel analysis using group mean centering. Results Controlling for social stressors, work interruptions, and emotional stability, the experience of more illegitimate tasks was associated with increased cortisol release if personal health resources were low compared to one’s mean value of perceived health. Results cannot be explained by inter-individual differences. Conclusions This is the first study showing that illegitimate tasks predict a biological indicator of stress, thus confirming and extending previous research on illegitimate tasks. The moderating role of perceived health confirms its importance as a personal resource, implying augmented vulnerability when perceived health is below its usual value. It is plausible to assume that increased stress reactions due to relatively poor health may further weaken available personal resources. Both avoiding illegitimate tasks and restoring personal health seem to be crucial.

Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism

Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using 41Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary 41Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700 days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary 41Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary 41Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the 41Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary 41Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated 41Ca/40Ca isotope ratios in urine were significantly lower than the observed 41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying relative changes in transfer rates between compartments in response to an intervention, inaccuracies in the underlying model cancel out. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While changes in bone formation and resorption can, in principle, be assessed by monitoring urinary 41Ca excretion over the first few weeks post-dosing, assessment of an intervention effect is more reliable approximately 150 days post-dosing when excreted tracer originates mainly from bone.

Illegitimate Tasks: Accumulating Evidence for a New Stressor Concept

INTRODUCTION: Task stressors typically refer to characteristics such as not having enough time or resources, ambiguous demands, or the like. We suggest the perceived lack of legitimacy as an additional feature of tasks as a source of stress. Tasks are “illegitimate” to the extent that it is perceived as improper to expect employees to execute them – not because of difficulties in executing them, but because of their content for a given person, time, and situation; they are illegitimate because a) they are not conforming to a specific occupational role, as in “non-nursing activities” (called unreasonable) or b) there is no legitimate need for them to exist (called unnecessary; Semmer et al., 2007). These features make illegitimate tasks a unique task-related stressor. The concept of illegitimate tasks grew from the “Stress-as-Offense-to-Self” theory (SOS; Semmer et al, 2007); it is conceptually related to role stress (Kahn et al., 1964; Beehr & Glazer, 2005) and the organizational justice tradition (Cropanzano et al., 2001; Greenberg, 2010). SOS argues that a threat to one’s self-image is at the core of many stressful experiences. Violating role expectations, illegitimate tasks can be regarded as a special case of role conflict. As roles shape identities, this violation is postulated to constitute a threat to one’s professional identity. Being assigned a task considered illegitimate is likely to be considered unfair. Lack of fairness, in turn, contains a message about one’s social standing, and thus, the self. However, the aspects discussed have not received much attention in the role stress or the justice/fairness tradition. OBJECTIVE: Illegitimate tasks are a rather recent concept that has to be established as a construct in its own right by showing that it is associated with well-being/strain while controlling for other stressors, most notably role conflict and lack of justice. The aim of the presentation is to present the evidence accumulated so far. METHODS AND RESULTS: We present several studies employing different designs, using different control variables, and testing associations with different criteria. Study 1 demonstrates associations of illegitimate tasks with self-esteem, feelings of resentment against one’s organization, and burnout, controlling for distributive justice, role conflict, and social stressors (i.e. tensions). Study 2 yielded comparable results, using the same outcome variables but controlling for distributive as well as procedural / interactional justice. Study 3 demonstrated associations between illegitimate tasks and feelings of stress, sleeping problems, and emotional exhaustion, controlling for demands, control, and social support among medical doctors. Study 4 showed that feeling appreciated by one’s superior acted as a mediator between illegitimate tasks and job satisfaction and resentments towards the military in Swiss military officers. Study 5 demonstrated an association of illegitimate tasks with counterproductive work behavior (Semmer et al. 2010). Studies 1 to 5 were cross-sectional. In Study 6, illegitimate demands predicted irritability and resentments towards one’s organization longitudinally. Study 7 also was longitudinal, focusing on intra-individual variation in multilevel modeling; occasion-specific illegitimate tasks predicted cortisol among those who judged their health as comparatively poor. Studies 1-3 and 6 used SEM, and measurement models that used unreasonable and unnecessary tasks as indicators (isolated parceling) yielded a good fit. IMPLICATIONS & CONCLUSIONS: These studies demonstrate that illegitimate tasks are a stressor in its own right that is worth studying. It illuminates the social meaning of job design, emphasizing the implications of tasks for the (professional) self, and thus combining aspects that are traditionally treated as separate, that is, social aspects and task characteristics. Practical implications are that supervisors and managers should be alerted to the social messages that may be contained in task assignments (cf. Semmer & Beehr, in press).

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.

Chapter Six – Individual Trait Variation and Diversity in Food Webs

In recent years, there has been a renewed interest in the ecological consequences of individual trait variation within populations. Given that individual variability arises from evolutionary dynamics, to fully understand eco-evolutionary feedback loops, we need to pay special attention to how standing trait variability affects ecological dynamics. There is mounting empirical evidence that intra-specific phenotypic variation can exceed species-level means, but theoretical models of multi-trophic species coexistence typically neglect individual-level trait variability. What is needed are multispecies datasets that are resolved at the individual level that can be used to discriminate among alternative models of resource selection and species coexistence in food webs. Here, using one the largest individual-based datasets of a food web compiled to date, along with an individual trait-based stochastic model that incorporates Approximate Bayesian computation methods, we document intra-population variation in the strength of prey selection by different classes or predator phenotypes which could potentially alter the diversity and coexistence patterns of food webs. In particular, we found that strongly connected individual predators preferentially consumed common prey, whereas weakly connected predators preferentially selected rare prey. Such patterns suggest that food web diversity may be governed by the distribution of predator connectivity and individual trait variation in prey selection. We discuss the consequences of intra-specific variation in prey selection to assess fitness differences among predator classes (or phenotypes) and track longer term food web patterns of coexistence accounting for several phenotypes within each prey and predator species.

Intra-subject variability in attention-deficit hyperactivity disorder

BACKGROUND: This study is based on a comprehensive survey of the neuropsychological attention-deficit hyperactivity disorder (ADHD) literature and presents the first psychometric analyses of different parameters of intra-subject variability (ISV) in patients with ADHD compared to healthy controls, using the Continuous Performance Test, a Go-NoGo task, a Stop Signal Task, as well as N-back tasks. METHODS: Data of 57 patients with ADHD and 53 age- and gender-matched controls were available for statistical analysis. Different parameters were used to describe central tendency (arithmetic mean, median), dispersion (standard deviation, coefficient of variation, consecutive variance), and shape (skewness, excess) of reaction time distributions, as well as errors (commissions and omissions). RESULTS: Group comparisons revealed by far the strongest effect sizes for measures of dispersion, followed by measures of central tendency, and by commission errors. Statistical control of ISV reduced group differences in the other measures substantially. One (patients) or two (controls) principal components explained up to 67% of the inter-individual differences in intra-individual variability. CONCLUSIONS: Results suggest that, across a variety of neuropsychological tests, measures of ISV contribute best to group discrimination, with limited incremental validity of measures of central tendency and errors. Furthermore, increased ISV might be a unitary construct in ADHD.

Individual and group level trajectories of behavioural development in Border collies.

In order to assess dogs’ personality changes during ontogeny, a cohort of 69 Border collies was followed up from six to 18–24 months. When the dogs were 6, 12, and 18–24 months old, their owners repeatedly filled in a dog personality questionnaire (DPQ), which yielded five personality factors divided into fifteen facets. All five DPQ factors were highly correlated between the three age classes, indicating that the dogs’ personality remained consistent relative to other individuals. Nonetheless, at the group level significant changes with age were found for four of the five DPQ factors. Fearfulness, Aggression towards People, Responsiveness to Training and Aggression towards Animals increased with age; only Activity/Excitability did not change significantly over time. These changes in DPQ factor scores occurred mainly between the ages of 6 and 12 months, although some facets changed beyond this age. No sex differences were found for any of the tested factors or facets, suggesting that individual variation in personality was greater than male/female differences. There were significant litter effects for the factors Fearfulness, Aggression towards People and Activity/Excitability, indicating either a strong genetic basis for these traits or a high influence of the shared early environment. To conclude, from the age of six months, consistency in personality relative to other individuals can be observed in Border collies. However, at the group level, increases in fearful and aggressive behaviours occur up to 12 months and for some traits up to two years, highlighting the need for early interventions. Follow-up studies are needed to assess trajectories of personality development prior to six months and after two years, and to include a wider variety of breeds.

A method to measure the distribution of latencies of motor evoked potentials in man

To measure the intra-individual distribution of the latencies of motor evoked potentials (MepL) using transcranial magnetic stimulation.