Using simulation studies to evaluate statistical methods

Simulation studies are computer experiments that involve creating data by pseudorandom sampling. The key strength of simulation studies is the ability to understand the behaviour of statistical methods because some 'truth' (usually some parameter/s of interest) is known from the process of generating the data. This allows us to consider properties of methods, such as bias. While widely used, simulation studies are often poorly designed, analysed and reported. This tutorial outlines the rationale for using simulation studies and offers guidance for design, execution, analysis, reporting and presentation. In particular, this tutorial provides: a structured approach for planning and reporting simulation studies, which involves defining aims, data-generating mechanisms, estimands, methods and performance measures ('ADEMP'); coherent terminology for simulation studies; guidance on coding simulation studies; a critical discussion of key performance measures and their estimation; guidance on structuring tabular and graphical presentation of results; and new graphical presentations. With a view to describing recent practice, we review 100 articles taken from Volume 34 of Statistics in Medicine that included at least one simulation study and identify areas for improvement.Comment: 31 pages, 9 figures (2 in appendix), 8 tables (1 in appendix

Integrated sampling-and-sensing using microdialysis and biosensing by particle motion for continuous cortisol monitoring

Microdialysis catheters are small probes that allow sampling from biological systems and human subjects with minimal perturbation. Traditionally, microdialysis samples are collected in vials, transported to a laboratory, and analysed with typical turnaround times of hours to days. To realize a continuous sampling-and-sensing methodology with minimal time delay, we studied the integration of microdialysis sampling with a sensor for continuous biomolecular monitoring based on Biosensing by Particle Motion (BPM). A microfluidic flow cell was designed with a volume of 12 μl in order to be compatible with flowrates of microdialysis sampling. The analyte recovery and the time characteristics of the sampling-and-sensing system were studied using a food colorant in buffer and using cortisol in buffer and in blood plasma. Concentration step functions were applied, and the system response was measured using optical absorption and a continuous BPM cortisol sensor. The cortisol recovery was around 80% for a 30 mm microdialysis membrane with a 20 kDa molecular weight cut-off and a flowrate of 2 μl min−1. The concentration-time data could be fitted with a transport delay time and single-exponential relaxation curves. The total delay time of the sampling-and-sensing methodology was about 15 minutes. Continuous sampling-and-sensing was demonstrated over a period of 5 hours. These results represent an important step toward integrated sampling-and-sensing for the continuous monitoring of a wide variety of low-concentration biomolecular substances for applications in biological and biomedical research.</p

Integrated sampling-and-sensing using microdialysis and biosensing by particle motion for continuous cortisol monitoring

Microdialysis catheters are small probes that allow sampling from biological systems and human subjects with minimal perturbation. Traditionally, microdialysis samples are collected in vials, transported to a laboratory, and analysed with typical turnaround times of hours to days. To realize a continuous sampling-and-sensing methodology with minimal time delay, we studied the integration of microdialysis sampling with a sensor for continuous biomolecular monitoring based on Biosensing by Particle Motion (BPM). A microfluidic flow cell was designed with a volume of 12 μl in order to be compatible with flowrates of microdialysis sampling. The analyte recovery and the time characteristics of the sampling-and-sensing system were studied using a food colorant in buffer and using cortisol in buffer and in blood plasma. Concentration step functions were applied, and the system response was measured using optical absorption and a continuous BPM cortisol sensor. The cortisol recovery was around 80% for a 30 mm microdialysis membrane with a 20 kDa molecular weight cut-off and a flowrate of 2 μl min−1. The concentration-time data could be fitted with a transport delay time and single-exponential relaxation curves. The total delay time of the sampling-and-sensing methodology was about 15 minutes. Continuous sampling-and-sensing was demonstrated over a period of 5 hours. These results represent an important step toward integrated sampling-and-sensing for the continuous monitoring of a wide variety of low-concentration biomolecular substances for applications in biological and biomedical research.</p

A breached barrier : analysis of stratum corneum lipids and their role in eczematous patients

The stratum corneum is the outermost layer of the skin, and acts as the primary barrier against penetration of pathogens, allergens and other exogenous substances into the lower layers of the skin. Crucial for a proper barrier function are the lipids in the stratum corneum, mainly consisting of ceramides, free fatty acids, and cholesterol. These lipids are highly ordered stacked layers. In atopic eczema the skin barrier is impaired, but the exact role of the lipids is still uncertain. This thesis describes the importance of a proper composition and ordering of the stratum corneum lipids and their role in eczematous patients (atopic eczema and Netherton disease). The results demonstrate that patients suffering from a impaired skin barrier also show different lipid profile. In particular the carbon chain length of the lipids is notably reduced in these eczematous patients. Consequently, the stratum corneum lipids show a less ordered lipid arangement. This is the first time that a strong correlation is observed between the lipid composition, the lipid organization, and the skin barrier function. These studies therefore provide new targets for possible drug therapy of eczematous patients.STW, Astellas, Evonik, RiverD, UnileverUBL - phd migration 201