Model-based data analysis of individual human postprandial plasma bile acid responses indicates a major role for the gallbladder and intestine

BACKGROUND: Bile acids are multifaceted metabolic compounds that signal to cholesterol, glucose, and lipid homeostasis via receptors like the Farnesoid X Receptor (FXR) and transmembrane Takeda G protein-coupled receptor 5 (TGR5). The postprandial increase in plasma bile acid concentrations is therefore a potential metabolic signal. However, this postprandial response has a high interindividual variability. Such variability may affect bile acid receptor activation. METHODS: In this study, we analyzed the inter- and intraindividual variability of fasting and postprandial bile acid concentrations during three identical meals on separate days in eight healthy lean male subjects using a statistical and mathematical approach. MAIN FINDINGS: The postprandial bile acid responses exhibited large interindividual and intraindividual variability. The individual mathematical models, which represent the enterohepatic circulation of bile acids in each subject, suggest that interindividual variability results from quantitative and qualitative differences of distal active uptake, colon transit, and microbial bile acid transformation. Conversely, intraindividual variations in gallbladder kinetics can explain intraindividual differences in the postprandial responses. CONCLUSIONS: We conclude that there is considerable inter- and intraindividual variation in postprandial plasma bile acid levels. The presented personalized approach is a promising tool to identify unique characteristics of underlying physiological processes and can be applied to investigate bile acid metabolism in pathophysiological conditions

Investigations of a compartmental model for leucine kinetics using nonlinear mixed effects models with ordinary and stochastic differential equations

Nonlinear mixed effects models represent a powerful tool to simultaneously analyze data from several individuals. In this study a compartmental model of leucine kinetics is examined and extended with a stochastic differential equation to model non-steady state concentrations of free leucine in the plasma. Data obtained from tracer/tracee experiments for a group of healthy control individuals and a group of individuals suffering from diabetes mellitus type 2 are analyzed. We find that the interindividual variation of the model parameters is much smaller for the nonlinear mixed effects models, compared to traditional estimates obtained from each individual separately. Using the mixed effects approach, the population parameters are estimated well also when only half of the data are used for each individual. For a typical individual the amount of free leucine is predicted to vary with a standard deviation of 8.9% around a mean value during the experiment. Moreover, leucine degradation and protein uptake of leucine is smaller, proteolysis larger, and the amount of free leucine in the body is much larger for the diabetic individuals than the control individuals. In conclusion nonlinear mixed effects models offers improved estimates for model parameters in complex models based on tracer/tracee data and may be a suitable tool to reduce data sampling in clinical studies

Cognitive Deficits Are Associated with Frontal and Temporal Lobe White Matter Lesions in Middle-Aged Adults Living in the Community

BACKGROUND The association between brain white matter lesions and cognitive impairment in old age is well established. However, little is known about this association in midlife. As this information will inform policy for early preventative healthcare initiatives, we investigated non-periventricular frontal, temporal, parietal and occipital lobe white matter hyperintensities (WMH) in relation to cognitive function in 428 (232 women) community-dwelling adults aged 44 to 48 years. RESULTS Frontal white matter lesions were significantly associated with greater intraindividual RT variability in women, while temporal WMH were associated with face recognition deficits in men. Parietal and occipital lobe lesions were unrelated to cognitive performance. These findings did not differ when education and a range of health variables, including vascular risk factors, were taken into account. CONCLUSION Gender differences in WMH-cognition associations are discussed, and we conclude that small vessel disease is present in midlife and has functional consequences which are generally not recognized. Preventative strategies should, therefore, begin early in life.David Bunce's collaboration in this work was supported by the Leverhulme Trust and the British Academy. The study was funded by NHMRC of Australia Unit Grant No. 973302, Program Grant No. 179805, NHMRC project grant No. 157125, grants from the Australian Rotary Health Research Fund and the Australian Brewers Foundation. Nicolas Cherbuin is funded by NHMRC Research Fellowship No. 471501. Kaarin Anstey is funded by NHMRC Research Fellowship No. 366756. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

The median frequency of the surface EMG power spectrum in relation to motor unit firing and action potential properties

Three components determine the power spectrum of the surface EMG signal: the auto- and cross-power spectra of the firing processes and the power spectra of the motor unit action potential (MUAP). To clarify the relative contribution of these components to the median frequency (MF) of the power spectrum, a stochastic simulation model was used in which most input parameters [e.g., MUAP peak-peak time (PPT), mean interpulse interval time, and synchronization parameters] were described in terms of distribution functions. Simulation clearly predicts that MF is especially sensitive to variations in MUAP shape, the MUAP PPT, and synchronization. The influence of the firing process parameters was predicted to be marginal. To obtain values for the MUAP parameters, a needle-triggered averaging technique was used to gather surface MUAPs from the m. biceps brachii. With use of these MUAPs as input for the model, it was found that intrasubject variability of MF is caused by variations in both MUAP PPT and MUAP shape, whereas intersubject variability in MF is caused primarily by variations in PPT

Engajamento no trabalho: um estudo das mudanças diárias

This research aimed to verify the daily intraindividual and interindividualvariations of work engagement and to investigate the predictors of this phenomenon and of the role performance at work, as well as the mediating role of engagement in the relationship between these predictors and performance. The sample consisted of 116 workers of both sexes (71.9% female). Through multilevel modelling, it could be identified that role ambiguity constituted a significant and negative predictor of engagement and performance, while participation in decision-making was characterized as a positive predictive variable of both constructs. The task complexity, in turn, proved to be a negative predictor of performance. Contrary to expectations, engagement did not show intra-individual variations. Brazilian organizations can benefit from these findings and seek to intervene in the work context.La presente investigación buscó verificar las fluctuaciones diarias intraindividuales del engagementlaboral e investigar los predictores de este fenómeno y del desempeño de rolesen el trabajo, así como el rol de mediación del engagementen la relación entre tales predictores y el desempeño. La muestra fue compuesta por 116 trabajadores, de ambos sexos (71,9% del sexo femenino). Por medio del modelado multinivel, fue posible identificar que la ambigüedad de papeles se constituyó en un predictor significativo y negativo del engagement y del desempeño, mientras que la participación en la toma de decisión se caracterizó como una variable predictora positiva de ambos constructos. La complejidad de la tarea, a su vez, reveló una predicción negativa del desempeño. Al contrario de lo que se esperaba, el engagementno presentó variaciones intraindividuales. Las organizaciones brasileñas pueden beneficiarse de estos hallazgos y buscar intervenir en el contexto de trabajo.Esta pesquisa teve como objetivo verificar as variações diárias intraindividuais e interindividuais do engajamento no trabalho e investigar os preditores desse fenômeno e do desempenho no trabalho, bem como o papel mediador do engajamento na relação entre esses preditores e o desempenho. A amostra foi constituída por 116 trabalhadores de ambos os sexos (71,9% do sexo feminino). Por meio da modelagem multinível, identificou-se que a ambiguidade de papel constituiu-se em um preditor significativo e negativo do engajamento e do desempenho, enquanto a participação na tomada de decisão caracterizou-se como uma variável preditiva positiva de ambos os construtos. A complexidade da tarefa, por sua vez, foi um preditor negativo do desempenho. Ao contrário do que se esperava, o engajamento não mostrou variações intraindividuais. As organizações brasileiras podem se beneficiar dessas descobertas e procurar intervir no contexto do trabalho

Utility of intraindividual reaction time variability to predict white matter hyperintensities: a potential assessment tool for clinical contexts?

Intraindividual variability (IIV) refers to reaction time (RT) variation across the trials of a given cognitive task. Little research has contrasted different measures of IIV or assessed how many RT trials are required to provide a robust measure of the construct. We, therefore, investigated three measures of IIV (raw SD, coefficient of variation, and intraindividual SD statistically removing time-on-task effects) in relation to frontal white matter hyperintensities (obtained through structural MRI) in 415 cognitively normal community-dwelling adults aged 44 to 48 years. Results indicated the three IIV measures did not differ greatly in predictions of white matter hyperintensities, although it is possible that time-on-task effects were influential. As few as 20 trials taking approximately 52 s to administer provided a reliable prediction of frontal white matter hyperintensities. We conclude that future work should evaluate the comparative utility of different IIV measures in relation to persons exhibiting clear neuropathology.NHMRC (National Health and Medical Research Council of Australia

The Role of Intraindividual Carotid Artery Variation in the Development of Atherosclerotic Carotid Artery Disease: A Literature Review

Carotid artery disease (CAD) is associated with numerous risk factors, including hypertension, hyperlipidemia, hypercholesterolemia, diabetes mellitus, and smoking. These systemic risk factors do not affect the carotid arteries equally in most patients, resulting in asymmetrical bilateral and unilateral CAD. It is unclear if anatomic variations in the carotid arteries predispose an individual to formation of atherosclerotic CAD. We wanted to assess (1) the inter-individual or intra-individual anatomical variations in the carotid arteries and (2) whether anatomical variations predispose the development of atherosclerotic CAD. PubMed and Medline were utilized to identify relevant literature for critical appraisal, summarization and documentation. Inclusion and exclusion criteria were applied to narrow results and articles were critically appraised and analyzed. Evidence suggests that a low outflow/inflow ratio, elevated bifurcation height, and bifurcation angle are associated with increased risk for CAD. Sex and age demonstrated positive correlation with the disease. Additionally, tortuosity and kinking of the carotid arteries may affect the formation of CAD but coiling of the arteries is a natural age-dependent process and does not affect CAD development. This review suggests there are anatomic variations in the carotid arteries that increase the risk of developing carotid artery disease. The most significant risk factors include a low outflow/inflow ratio, increased internal carotid artery tortuosity, elevated bifurcation height, and bifurcation angle