Skills and Expertise
Research Items (262)
Das Buch bietet eine Einführung in die statistische Datenanalyse unter Verwendung der freien Statistiksoftware R, der derzeit wohl mächtigsten Statistiksoftware. Die Analysen werden anhand realer Daten durchgeführt und besprochen. Nach einer kurzen Beschreibung der Statistiksoftware R werden wichtige Kenngrößen und Diagramme der deskriptiven Statistik vorgestellt. Anschließend werden Empfehlungen für die Erstellung von Diagrammen gegeben, wobei ein spezielles Augenmerk auf die Auswahl geeigneter Farben gelegt wird. Die zweite Hälfte des Buches behandelt die Grundlagen der schließenden Statistik. Zunächst wird eine Reihe von Wahrscheinlichkeitsverteilungen eingeführt und deren Anwendungen anhand von Beispielen illustriert. Es folgt eine Beschreibung, wie die in der Praxis unbekannten Parameter der Verteilungen auf Basis vorliegender Daten geschätzt werden können. Im abschließenden Kapitel werden statistische Hypothesentests eingeführt und die für die Praxis wichtigsten Tests besprochen.
The book offers an introduction to statistical data analysis applying the free statistical software R, probably the most powerful statistical software today. The analyses are performed and discussed using real data. After a brief description of the statistical software R, important parameters and diagrams of descriptive statistics are introduced. Subsequently, recommendations for generating diagrams are provided, where special attention is given to the selection of appropriate colors. The second half of the book addresses the basics of inferential statistics. First, a number of probability distributions are introduced and their applicability is illustrated by examples. Next, the book describes how the parameters of these distributions, which are unknown in practice, may be estimated from given data. The final chapter introduces statistical tests and reviews the most important tests for practical applications.
Measuring gene transcription using real-time reverse transcription polymerase chain reaction (RT-qPCR) technology is a mainstay of molecular biology. Technologies now exist to measure the abundance of many transcripts in parallel. The selection of the optimal reference gene for the normalisation of this data is a recurring problem, and several algorithms have been developed in order to solve it. So far nothing in R exists to unite these methods, together with other functions to read in and normalise the data using the chosen reference gene(s). We have developed two R/Bioconductor packages, ReadqPCR and NormqPCR, intended for a user with some experience with high-throughput data analysis using R, who wishes to use R to analyse RT-qPCR data. We illustrate their potential use in a workflow analysing a generic RT-qPCR experiment, and apply this to a real dataset. Packages are available from http://www.bioconductor.org/packages/release/bioc/html/ReadqPCR.htmland http://www.bioconductor.org/packages/release/bioc/html/NormqPCR.html These packages increase the repetoire of RT-qPCR analysis tools available to the R user and allow them to (amongst other things) read their data into R, hold it in an ExpressionSet compatible R object, choose appropriate reference genes, normalise the data and look for differential expression between samples.
Question - Several ROC-curves in one graph, using R
For modern approaches in precision medicine, fast and easy-to-use point-of-care diagnostics (POCs) are essential. Digoxin was chosen as an example of a drug requiring close monitoring. Digoxin is a cardiac glycoside used for the treatment of tachycardia with a narrow therapeutic window of 0.5–2.0 ng·mL⁻¹, and toxic effects are common for concentrations above 2.5 ng·mL⁻¹. For monitoring of blood concentration levels and treatment of intoxication, highly selective antibodies for digoxin and its hapten, digoxigenin, are available. A smartphone readout system is described for measuring digoxigenin in human serum using a common gold nanoparticle lateral flow assay (LFA). The R-package GNSplex, which also includes a Shiny app for quantitative test interpretation based on linear models, is used for image analysis. Images of lateral flow strips were taken with an iPhone camera and a simple darkbox made from black cardboard. Sensitivity and accuracy of the quantitative smartphone system as well as analytical parameters such as limit of detection (LOD) were determined and compared to data obtained with a high resolution BioImager. The data show that the smartphone based digoxin assay yields reliable quantitative results within the clinically relevant concentration range. Graphical abstractFor therapeutic drug monitoring and point of care diagnostics we introduce the open source R-package GNSplex for smartphone readout and interpretation of lateral flow assays. The cardiac glycoside dixogin was used as target for this quantitative smartphone reader
Question - Classification vs. Regression in machine learning?
Question - How can I compute multivariate ROC curves?
Question - Shapiro-Wilk test instead of the Kolmogorov-Smirnov for large sample sizes?
As the sample size is large and as there are many central limit theorems that might apply to your situation, the question for me is whether testing for normality is really of relevance.
Introduction. Recent meta-analyses on compression garments have reported faster recovery of muscle function particularly after intense eccentric power or resistance exercise. However, due to the complex interaction between cohorts included, exercises involved and compression applied, recovery length and modalities, and outcome parameters selected, only limited practical recommendations can be drawn from these studies. Thus, our aim was to determine the effect of compression tights on recovery from high mechanical and metabolic stress monitored over a longer recovery period. Material and Methods. Using a crossover design, 19 resistance-trained 4th/5th Division German handball players (31.3±7.7 years; 24.1±3.8 kg/m2) were randomly assigned at the start of the project to the compression tight (recovery-pro-tights, cep, Bayreuth, Germany) or the control group. Immediately after a combined lower extremity resistance training and electromyostimulation, participants had to wear compression tights. Compression was applied initially for 24 h and then 12 h intermitted by 12 h of nonuse for a total of 96 h. Primary study endpoint was maximum isokinetic hip/leg-extensor strength (MIES) as determined by a leg-press. Secondary endpoint was lower extremity power as assessed by a counter movement jump. Follow-up assessments were conducted 24, 48, 72, and 96 h postexercise. Outcomes were analyzed using a linear mixed effect model with spherical symmetric within-condition correlation. Results. All 19 participants underwent their allocated treatment and passed through the project strictly according to the study protocol. MIES demonstrated significantly (p=0.003) lower overall reductions (155 N) after wearing compression tights. In parallel, lower extremity power significantly (p
Question - NA's in the dataset?
What about your independent variables? Maybe you could try some unsupervised statistical learning and see what clusters/structures you get and whether there is some association with your dependent variable (which could also be the frequency of NA) ...
Question - How to do validation after doing normalization in microarray?
Caveat: In case of quantile normalization the boxplots will always look perfect, as the idea of quantile normalization is to become normalized distributions that are identical for all the arrays.
Question - How to do validation after doing normalization in microarray?
Mainly by diagnostic plots such as boxplots (not in case of quantile normalization), Mean-Sd-Plots (homoscedasticity), similarity maps (outliers), etc.
Background: Sarcopenic Obesity (SO) is characterized by low lean and high fat mass; i.e. from a functional aspect a disproportion between engine (muscle) and mass to be moved (fat). At present, most research focuses on the engine, but the close "cross talk" between age-associated adipose and skeletal muscle tissue inflammation calls for comprehensive interventions that affect both components alike. Protein and exercise are likely candidates, however with respect to the latter, the enthusiasm for intense and frequent exercise is rather low, especially in functionally limited older people. The aim of this study was therefore to evaluate the effect of whole-body electromyostimulation (WB-EMS), a time-efficient, joint-friendly and highly customizable exercise technology, on obesity parameters and cardiometabolic risk in men with SO. Methods: One-hundred community-dwelling (cdw) Bavarian men ≥70 years with SO were randomly assigned to either (a) whey protein supplementation (WPS), (b) WB-EMS and protein supplementation (WB-EMS&P) or (c) non-intervention control (CG). Protein supplementation contributed to an intake of 1.7-1.8 g/kg/body mass/d, WB-EMS consisted of 1.5 × 20 min/week (85 Hz, 350 μs, 4 s of strain-4 s of rest) with moderate-high intensity. Using an intention to treat approach with multiple imputation, the primary study endpoint was total body fat mass (TBF), secondary endpoints were trunk fat mass (TF), waist circumference (WC) and total-cholesterol/HDL-cholesterol ratio (TC/HDL-C). Results: After 16 weeks of intervention, TBF was reduced significantly in the WPS (- 3.6 ± 7.2%; p = 0.005) and WB-EMS&P (- 6.7 ± 6.2%; p < 0.001), but not in the CG (+ 1.6 ± 7.1%; p = 0.191). Changes in the WB-EMS&P (p < 0.001) and the WPS group (p = 0.011) differ significantly from the CG. TF decreased in the WB-EMS&P (p < 0.001) and WPS (p = .117) and increased in the CG (p = .159); WC decreased significantly in the treatment groups and was maintained in the CG. Lastly, the TC/HDL-C ratio improved significantly in the WB-EMS&P and WPS group and was maintained in the CG. Significant differences between WB-EMS&P and WPS were determined for waist circumference only (p = 0.015; TBF: p = 0.073; TF: p = 0.087; TC/HDL-C: p = .773). Conclusion: Moderate-high dosed whey protein supplementation, especially when combined with WB-EMS, may be a feasible choice to address obesity and cardiometabolic risk in older cdw men with SO unable or unmotivated to exercise conventionally. Trial registration number: ClinicalTrials.gov NCT02857660 ; registration date: 05/01/2017.
Surfaces with regular contact with the human body are typically contaminated with microorganisms and might be considered as fomites. Despite spectacles being widespread across populations, little is known about their microbial contamination. Therefore, we swab-sampled 11 worn spectacles within a university setting as well as 10 worn spectacles in a nursing home setting. The microbial load was determined by aerobic cultivation. All spectacles were found to be contaminated with bacteria, with nose pads and ear clips having the highest density, i.e. at sites with direct skin contact. Summed over all sites, the median microbial load of the university spectacles (1.4 ± 10.7 x 10³ CFU cm⁻²) did not differ significantly from the spectacles tested in the nursing home (20.8 ± 39.9 x 10³ CFU cm⁻²). 215 dominant bacterial morphotypes were analyzed by MALDI biotyping. 182 isolates could be assigned to 10 genera, with Staphylococcus being the most common. On genus-level, bacterial diversity was greater on nursing home spectacles (10 genera) compared to the university environment (2 genera). Four cleaning methods were investigated using lenses artificially contaminated with Escherichia coli, Micrococcus luteus, a 1:2 mixture of E. coli and M. luteus, and Staphylococcus epidermidis (the dominant isolate in our study), respectively. Best cleaning results (99% -100% median germ reduction) were obtained using impregnated wipes; dry cleaning was less effective (85% -90% median germ reduction). Finally, 10 additional worn university spectacles were cleaned with wipes impregnated with an alcohol-free cleaning solution before sampling. The average bacterial load was significantly lower (0.09 ± 0.49 x 10³ CFU cm⁻²) compared to the uncleaned university spectacles previously investigated. Spectacles are significantly contaminated with bacteria of mostly human skin origin—including significant amounts of potentially pathogenic ones and may contribute to eye infections as well as fomites in clinical environments.
Age-related loss of muscle mass and function, also called sarcopenia, was recently added to the ICD-10 as an independent condition. However, declines in muscle mass and function are inevitable during the adulthood aging process. Concerning muscle strength as a crucial aspect of muscle function, maximum knee extension strength might be the most important physical parameter for independent living in the community. In this study, we aimed to determine the age-related decline in maximum isokinetic knee extension (MIES) and flexion strength (MIFS) in adult men. The primary study hypothesis was that there is a slight gradual decrease of MIES up to ≈age 60 years with a significant acceleration of decline after this “changepoint.” We used a closed kinetic chain system (leg-press), which is seen as providing functionally more relevant results on maximum strength, to determine changes in maximum isokinetic hip/leg extensor (MIES) and flexor strength (MIFS) during adulthood in men. Apart from average annual changes, we aimed to identify whether the decline in maximum lower extremity strength is linear. MIES and MIFS data determined by an isokinetic leg-press of 362 non-athletic, healthy, and community-dwelling men 19–91 years old were included in the analysis. A changepoint analysis was conducted based on a multiple regression analysis adjusted for selected co-variables that might confound the proper relationship between age and maximum strength. In summary, maximum isokinetic leg-strength decline during adulthood averaged around 0.8–1.0% p.a.; however, the reduction was far from linear. MIES demonstrated a non-significant reduction of 5.2 N/p.a. (≈0.15% p.a.) up to the estimated breakpoint of 52.0 years and an accelerated loss of 44.0 N/p.a. (≈1.3% p.a.; p < 0.001). In parallel, the decline in MIFS (10.0 N/p.a.; ≈0.5% p.a.) prior to the breakpoint at age 59.0 years was significantly more pronounced. Nevertheless, we observed a further marked accelerated loss of MIFS (25.0 N/p.a.; ≈1.3% p.a.) in men ≥60 years. Apart from the “normative value” and closed kinetic chain aspect of this study, the practical application of our results suggests that sarcopenia prophylaxis in men should be started in the 5th decade in order to address the accelerated muscle decline of advanced age.
Question - If I fit a linear mixed effects model using lme() function (in nlme package in r), Can I get the the conditional standard deviation?
Question - How to calculate post-hoc power for multilevel model comparison?
- Oct 2018
Objective: To analyze the short-term thermogenic effects of footbaths with warm water alone (WA) versus when combined with medicinal powders. Design: Randomized controlled trial with cross-over. Interventions and Outcomes: Seventeen healthy volunteers (mean age 22.1 years, SD = 2.4; 11 female) received three footbaths with WA or WA combined with mustard (MU) or ginger (GI) in a randomized order. Self-perceived warmth (Herdecke warmth perception questionnaire) and actual skin temperatures (thermography) were assessed before (t0), immediately after footbaths (t1), and 10 minutes later (t2). The primary outcome was perceived warmth in the feet. Secondary outcomes were warmth perception in the face, hands and overall, as well as actual skin temperature in the feet, face, and hands. Results: Perceived warmth at the feet (primary outcome) increased significantly (all p's <.001) for MU and GI at t1 as well as for GI at t2 when compared to t0 with high effect sizes. At t2, GI differed significantly from WA (p <.001) and MU (p =.048). With regards to the secondary measures of outcome, no significant effects were seen for perceived warmth at the face or hands. Overall warmth was significantly higher at t1 compared to t0 (p =.01). Thermography assessments of skin temperature at the feet at t1 increased after all conditions (p <.001). No effects were seen in the face. At the hands, temperature decreased at t1 (p =.02) and t2 compared to t0 (p <.001). Conclusion: The present study provides preliminary evidence that mustard and ginger increase warmth perception at the feet more than warm water alone, with only the effects for GI enduring at the brief follow-up.
Purpose Low back pain (LBP) is one of the most frequent chronic conditions worldwide. Data from a recent meta-analysis indicated that whole-body electromyostimulation (WB-EMS), a time-effective, joint–friendly, and highly individualized training technology, demonstrated promising effects on LBP; however, methodologic limitations prevent definitive evidence for this result. Thus, the aim of this study was to conduct a randomized controlled WB-EMS trial to determine the corresponding effect on chronic, nonspecific LBP in people with chronic LBP. Patients and methods Thirty LBP patients, 40–70 years old, were randomly assigned into two groups (WB-EMS: 15; control [CG]: 15). While the nonactive CG maintained their lifestyle, the WB-EMS group completed a 12-week WB-EMS protocol (1×20 min/week) with slight movements, specifically dedicated to LBP. Pain intensity and frequency were determined by a 4-week pain diary before and during the last 4 weeks of intervention. Primary study endpoint was average pain intensity at the lumbar spine. Results At baseline, no group differences apart from nonregular exercise were observed. Mean intensity of LBP decreased significantly in the WB-EMS group (P=0.002) and remained unchanged in the CG (P=0.730), with a significant difference between both groups (P=0.027). Maximum isometric trunk extensors improved significantly in the WB-EMS group (P=0.005), while no significant difference was seen in the CG (P=0.683). In contrast to the significant difference between WB-EMS group and CG for the latter parameter (P=0.038), no intergroup difference was determined for maximum isometric trunk flexors (P=0.091). The WB-EMS group showed a significant increase of this parameter (P=0.003), while no significant change was determined in the CG (P=0.563). Conclusion WB-EMS is a time-effective training method for reducing chronic nonspecific LBP and increasing maximum trunk strength in people with such complaints. After this promising comparison with a nonactive CG, research needs to be extended to include comparisons with active groups (WB-Vibration, conventional back strengthening).
Package MKmisc includes a collection of functions that I found useful in my daily work. It contains several functions for statistical data analysis; e.g. for sample size and power calculations, computation of confidence intervals, and generation of similarity matrices.
Optimally robust estimation for extreme value distributions using S4 classes and methods (based on packages 'distr', 'distrEx', 'distrMod', 'RobAStBase', and 'ROptEst').
Background The aim of this strictly statistical approach was to provide a figure discrimination in a homogeneous cohort that is based on a main component, which includes disability, physical performance, and autonomy parameters. Methods We used data of 939 community-dwelling men aged ≥70 years, living in the area of Erlangen-Nürnberg, Germany. Briefly, we conducted a scaled principal component analysis based on criteria related to “physical function”, “disability”, “weakness”, and “autonomy” to identify men who are likely to have sarcopenia as per the recognized sarcopenia criteria. Next, we applied fast-and-frugal decision trees, logistic regression, and classification and regression decision trees to classify men with and without sarcopenia, applying the 5% prevalence rate identified for this cohort by recent studies. Results In summary, the best fast-and-frugal decision trees included gait velocity, handgrip strength, and two skeletal muscle mass indices (SMI) – appendicular skeletal muscle mass (ASMM)/body mass index (BMI) and ASMM/height². Briefly, men below the cutoff point of 1.012 m/s for gait velocity were directly classified as sarcopenic. Faster men with a handgrip strength of >34.5 kg were excluded from further screening, while their weaker peers were assessed for SMI. Firstly, an ASMM/BMI-based exclusion criterion of >0.886 indicates no sarcopenia; while in men with a lower BMI-based SMI, an ASMM/height² of <7.25 kg/m² indicates sarcopenia. Of importance, about 72% of the participants can be classified without an SMI assessment. Conclusion The present approach that applied recognized sarcopenia criteria and was based on a predominately functional understanding of sarcopenia provided a simple and feasible decision rule for sarcopenia discrimination. In summary, we consider our approach as a strictly biometrical contribution within the development of sarcopenia screening methods. However, our tool needs to be further evaluated to validate its appropriateness to discriminate sarcopenia in this relevant cohort.
Includes 'sysdata.rda' file for packages of the 'RobASt' - family of packages; is currently used by package 'RobExtremes' only.
- Jun 2018
Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli-induced increase of C16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis. Compounds like NB 06 thus offer highly interesting fields of application besides prevention of apoptosis of macrophages in atherosclerotic plaques in vessel walls. Most importantly, they can be used for blocking pH-dependent lysosomal processes and enzymes in general as well as for analyzing lysosomal dependent cellular signaling. Modulation of gene expression of several prominent inflammatory messengers IL1B, IL6, IL23A, CCL4 and CCL20 further indicate potentially beneficial effects in the field of (systemic) infections involving bacterial endotoxins like LPS or infections with influenza A virus.
The primary aim of the project was to determine the combined effect of whole-body electromyostimulation (WB-EMS) and protein supplements on local and overall muscle/fat distribution in older man with sarcopenic obesity (SO). Community-dwelling (cdw) men ≥ 70 years with SO were randomly allocated to a WB-EMS and protein supplementation (n = 33) or a non-intervention control group (CG: n = 34). WB-EMS was conducted 1.5 sessions of 20 min/week for 16 weeks. Whey protein supplementation aimed to ensure a daily intake of 1.8 g/kg body mass. The primary study endpoint was muscle/fat distribution of the total intra-fascial volume of the mid-thigh as determined by MRI. The core secondary endpoint was appendicular muscle mass (ASMM) and trunk fat; subordinate secondary endpoint was lower-leg performance. Thigh lean muscle volume increased significantly in the WB-EMS&P (p < 0.001) and increased slightly in the CG (p = 0.435). In parallel, fat volume increased significantly in the CG (p < 0.001) and was maintained in the WB-EMS&P group (p = 0.728). Group differences for both parameters were significant (p = 0.033 and p = 0.002). ASMM and trunk fat also differed significantly (p < 0.001) between WB-EMS and CG, with significant positive changes in the WB-EMS&P (p < 0.001) and no relevant changes in the CG (p ≥ 0.458). Finally, changes of gait velocity, leg-extensor strength, and advanced lower extremity function of the WB-EMS&P group differed significantly from the CG (p ≤ 0.002). WB-EMS combined with whey protein supplements favorably affects local and overall muscle/fat distribution and lower limb functioning in cdw men 70+ with SO. Thus, this time-saving, joint-friendly, and highly customizable approach may be an option for people either unable or unmotivated to conduct intense (resistance) exercise protocols.
This systematic review detected only limited positive effects of exercise on bone mineral density in older men. Further, based on the present literature, we were unable to suggest dedicated exercise prescriptions for this male cohort that might differ from recommendations based on studies with postmenopausal women. The primary aim of this systematic review was to determine the effect of exercise on bone mineral density (BMD) in healthy older men. A systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement included only randomized or non-randomized controlled trials of exercise training ≥ 6 months with study groups of ≥ eight healthy men aged 50 years or older, not using bone-relevant pharmacological therapy, that determined BMD by dual-energy X-ray absorptiometry. We searched PubMed, Scopus, Web of Science, Cochrane, Science Direct, and Eric up to November 2016. Risk of bias was assessed using the PEDro scale. We identified eight trials with 789 participants (PEDro-score, mean value 6 of 10) which satisfied our eligibility criteria. Studies vary considerably with respect to type and composition of exercise. Study interventions of six trials were considered to be appropriate for successfully addressing BMD in this cohort. Between-group differences were not or not consistently reported by three studies. Three studies reported significant exercise effects on BMD for proximal femur; one of them determined significant differences between the exercise groups. None of the exercise trials determined significant BMD effects at the lumbar spine. Based on the present studies, there is only limited evidence for a favorable effect of exercise on BMD in men. More well-designed and sophisticated studies on BMD in healthy older men have to address this topic. Further, there is a need to define intervention quality standards and implement a universal scoring system that allows this pivotal determinant to be addressed much more intensively.
Aptamer-based lateral flow assays (LFAs) are an emerging field of aptamer applications due to numerous potential applications. When compared to antibodies, potential advantages like cost effectiveness or lower batch to batch variations are evident. The development of LFAs for small molecules, however, is still challenging due to several reasons, primarily linked to target size and accessible interaction sites. In small molecule analysis, however, aptamers in many cases are preferable since immunogenicity is not required and they may exhibit even higher target selectivity. We report the first cross-recognition of a small molecule (ampicillin) and a protein (C-reactive protein), predicted by in-silico analysis, then experimentally confirmed - using two different aptamers. These features can be exploited for developing an aptamer-based LFA for label-free ampicillin detection, functioning also for analysis in milk extract. Most importantly, the principal setup denotes a novel, transferable and versatile general approach for detection of small molecules using competitive LFAs, unlikely to be generally realized by aptamer-DNA-binding otherwise.
Question - What is the most complete free software to score information in baseball?
I would go for R or Python.
Question - Which statistical test should I use for my data analysis?
Dear Mohsen Ashrafi,
I would say it depends whether and how you have pre-processed (normalized) the data.
Abstract Nanoparticles (NPs) and other nanomaterials are progressively studied for use in biomedical applications such as imaging, drug delivery, and hyperthermia therapies. Therefore, considering the interaction of nanomaterials with biological systems becomes vital for their safe and efficient application. It is increasingly being acknowledged that the surface of nanomaterials would be covered by protein corona upon their entrance to the biological medium. The biological medium will then see the achieved modified surface of nanomaterials, and therefore, further cellular/tissue responses depend on the composition of corona. Here, we explain that the corona differences according to the physicochemical properties of nanomaterials (e.g., size, structure, surface charge, surface functional groups, and hydrophobicity/hydrophobicity). Besides the nanomaterials' effects, the role of environment factors, such as protein source and slight temperature variations, is discussed in detail. Notwithstanding the publicity regarding the enormous and imminent profitable potential of nanotechnology, there is little distrust that NPs offer real and radically new opportunities in fields such as biomedicine and materials science, among others. Such particles are little enough to reach almost all areas of the body, including cells and organelles, potentially leading to a new approach to medicine (nanomedicine), including rational methodologies to targeted intracellular delivery of genes and other therapies. However, there have been extensive concerns that their use could involve some biological hazard and a growing consensus that our understanding of the interaction of nanoscale objects with living matter, even at the level of single cells, has not kept pace with the explosive development of nanoscience in the past decades. Protein-nanoparticle interactions in nanomedicine and nanotoxicity have started to arise newly with the improvement of the awareness of the NP-protein “corona.” This dynamic layer of proteins (and other biomolecules) adsorbs to NP surfaces as soon as it comes in interaction with organic systems. Whereas in the biomaterial field the importance of adsorbed molecules in cellular responses is recognized, there are numerous new issues at stake where NPs are concerned.
- Feb 2018
- Elsevier Science
Precision Medicine: Tools and Quantitative Approaches discusses precision and personalized medicine, two relevant topics that are revolutionizing diagnostics and treatment, while also providing a shift toward prevention. The book covers the most relevant features and explanations underlying developments in the field. A timely review on prerequisites, causes and consequences is given. Unique to this book is a combined view on technical and data analysis aspects that is mandatory for obtaining and interpreting results. This book is a valuable source for researchers in medical and life sciences, physicians and students with an interest in this emerging field of precision medicine.
Abstract Statistical (machine) learning more and more becomes a key tool for precision medicine. In this chapter, we describe the most important components and steps involved in statistical learning for patient data. We start with the basics such as the data itself and the types of learning algorithms. Next, we explain in more detail how supervised learning is performed. We give details about the steps that are involved, where some of the steps are optional and depend on the dataset at hand. Finally, we provide the sketch of a workflow that can be applied to derive predictive models and to evaluate their performance.
Question - How to use the EM bootstrap method in Amelia package in R?
for more details on the implementation you have to look at the help page of function amelia, which opens by running ?amelia or help("amelia"). The function returns the imputed datasets, but doesn't analyse and pool. Which kind of analysis do you want to perform on the imputed datasets?
Question - How fit Gamma to Lilliefors test in Rstudio?
this was a misunderstanding. I meant that you could estimate the parameters of the gamma distribution by means of the Kolmogorov-Smirnov minimum distance estimator using R package distrMod and then use these parameters in combination with function ks.test to perform the Kolmogorov-Smirnov test.
Question - How fit Gamma to Lilliefors test in Rstudio?
you could use the Kolmogorov-Smirnov minimum distance estimator from package distrMod to estimate the parameters and then apply function ks.test as shown in the examples section of the help page of ks.test.
The Lilliefors test is a specialisation of the Kolmogorov-Smirnov test to the normal distribution.
In testing for distributions the sample size is a crucial point. Using function qqplot of package distrMod would be an alternative to testing.
To determine the underlying mechanisms after one session of (intense) whole-body electromyostimulation (WB-EMS) on total energy expenditure (TEE) and resting metabolic rate (RMR), 16 subjects followed a standardized protocol of indirect calorimetry for up to 72h in 12h intervals. The single session significantly increased RMR about 25±10% (p<0.001) and TEE for about 9.5±1%, a net effect of ~460±50 kcal (WB-EMS vs. CG).
Background: Low back pain (LBP) has a high priority in our predominately sedentary society. The aim of this meta-analysis of present data was to evaluate the effect of whole-body electromyostimulation (WB-EMS) on LBP in sedentary older people with relevant pain. › Methods: The present analysis based on four recently-conducted randomized controlled WB-EMS trials (RCT). All of the trials included participants 60 years+ and used WB-EMS-protocols with comparable stimulation parameters (1.5 sessions/week, 16-25min/session, bipolar, 85Hz, 350μs, 4-6s impulse/4sec impulse- break) applied for 14-52 weeks. All the studies defined “strength” as a primary or secondary study-endpoint. We included only subjects with relevant LBP frequency in the present analysis (≥5 on a 0-7 scale). Of the 36 men (n=11) and women (n=25) sampled, 17 were participants in a WB-EMS-group and 19 subjects were in the corresponding control group (CG). › Results: At baseline, no group differences with respect to LBP intensity and frequency were observed. Pain intensity improved significantly in the WB-EMS (p<.001) and did not change (p=.834) in the CG. Group differences for pain intensity were significant (p=.012). LBP frequency, however, improved significantly in the WB-EMS (p<.001) and the CG (p=.042). Differences between WBEMS and CG were borderline non-significant (p=.050). › Conclusion: WB-EMS appears to be an effective training tool for reducing LBP. Nonetheless, effectiveness, feasibility and sustainability of this training technology should be addressed more intensively by further, more dedicated RCTs.
In order to evaluate the favorable effect of whole-body electromyostimulation (WB-EMS) on low back pain (LBP), an aspect which is frequently claimed by commercial providers, we performed a meta-analysis of individual patient data. The analysis is based on five of our recently conducted randomized controlled WB-EMS trials with adults 60 years+, all of which applied similar WB-EMS protocols (1.5 sessions/week, bipolar current, 16–25 min/session, 85 Hz, 350 μ s, and 4–6 s impulse/4 s impulse-break) and used the same pain questionnaire. From these underlying trials, we included only subjects with frequent-chronic LBP in the present meta-analysis. Study endpoints were pain intensity and frequency at the lumbar spine. In summary, 23 participants of the underlying WB-EMS and 22 subjects of the control groups (CG) were pooled in a joint WB-EMS and CG. At baseline, no group differences with respect to LBP intensity and frequency were observed. Pain intensity improved significantly in the WB-EMS ( p<.001 ) and was maintained ( p=.997 ) in the CG. LBP frequency decreased significantly in the WB-EMS ( p<.001 ) and improved nonsignificantly in the CG ( p=.057 ). Group differences for both LBP parameters were significant ( p≤.035 ). We concluded that WB-EMS appears to be an effective training tool for reducing LBP; however, RCTs should further address this issue with more specified study protocols.
- Oct 2017
Purpose of review: Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address fracture risk. The aims of the present article were to review and summarize the independent effect of exercise frequency (ExFreq) on the main determinants of fracture prevention, i.e., bone strength, fall frequency, and fall impact in older adults. Recent findings: Evidence collected last year suggests that there is a critical dose of ExFreq that just affects bone (i.e., BMD). Corresponding data for fall-related fracture risk are still sparse and inconsistent, however. The minimum effective dose (MED) of ExFreq that just favorably affects BMD at the lumbar spine and femoral neck has been found to vary between 2.1 and 2.5 sessions/week. Although this MED cannot necessarily be generalized to other cohorts, we speculate that this "critical exercise frequency" might not significantly vary among adult cohorts.
Purpose: Cancer patients are at high risk of malnutrition and tumor cachexia further increasing morbidity and mortality. Reasons for cachexia are not clear yet, but inflammatory processes as well as the occurrence of taste disorders reducing nutrient uptake are discussed to play key roles. The purpose of this study was to gain insight into causative factors of taste disturbance in cancer patients. Does the cancer itself, inflammatory processes or cancer therapy influence taste disorders? Methods: To capture an underlying taste disorder patients with cancer (n = 42), acutely hospitalized inflammatory disease patients (n = 57) and healthy controls (n = 39) were examined. To assess the influence of chemotherapy, patients with and without chemotherapy were compared. Taste tests were performed according to DIN ISO 3972:2011. Inflammation was recorded using laboratory parameters. Statistical evaluation was conducted using the Software R. Results: Cancer patients showed significantly increased taste thresholds for sweet, salty, and umami compared to healthy controls. There were no significant differences in taste detection and recognition between patients with former, current, or without chemotherapeutical treatment. Patients with an acute inflammatory disease showed an increased taste threshold for umami compared to healthy controls. Conclusions: It could be shown that cancer patients suffer from taste disorders irrespective of an existing chemotherapeutical treatment. Cancer-related inflammation appears to have a greater impact on taste perception than an acute inflammatory process. Therefore, an adapted dietary adjustment should be carried out at an early stage for cancer patients in order to avoid nutritional disorders caused by a taste disorder.
Background Sarcopenic obesity (SO) is a geriatric syndrome characterized by the disproportion between the amount of lean mass and fat mass. Exercise decreases fat and maintains muscle mass; however, older people fail to exercise at doses sufficient to affect musculoskeletal and cardiometabolic risk factors. The aim of this study was to evaluate the effect of whole-body electromyostimulation (WB-EMS), a time-efficient, joint-friendly and highly individualized exercise technology, on sarcopenia and SO in older men. Materials and methods A total of 100 community-dwelling northern Bavarian men aged ≥70 years with sarcopenia and obesity were randomly (1–1–1) assigned to either 16 weeks of 1) WB-EMS and protein supplementation (WB-EMS&P), 2) isolated protein supplementation or 3) nonintervention control. WB-EMS consisted of 1.5×20 min (85 Hz, 350 µs, 4 s of strain to 4 s of rest) applied with moderate-to-high intensity while moving. We further generated a daily protein intake of 1.7–1.8 g/kg/body mass per day. The primary study end point was Sarcopenia Z-Score, and the secondary study end points were body fat rate (%), skeletal muscle mass index (SMI) and handgrip strength. Results Intention-to-treat analysis determined a significantly favorable effect of WB-EMS&P (P<0.001) and protein (P=0.007) vs control. Both groups significantly (P<0.001) lost body fat (WB-EMS&P: 2.1%; protein: 1.1%) and differed significantly (P≤0.004) from control (0.3%). Differences between WB-EMS&P and protein were significant for the Sarcopenia Z-Score (P=0.39) and borderline nonsignificant (P=0.051) for body fat. SMI increased significantly in both groups (P<0.001 and P=0.043) and decreased significantly in the control group (CG; P=0.033); differences between the verum groups and control were significant (P≤0.009). Handgrip strength increased in the WB-EMS group (1.90 kg; P<0.001; P=0.050 vs control) only. No adverse effects of WB-EMS or protein supplementation were recorded. Conclusion WB-EMS&P is a safe and efficient method for tackling sarcopenia and SO in older men. However, the suboptimum effect on functional parameters should be addressed by increased voluntary activation during WB-EMS application.
- Jul 2017
Despite its frequent use in many religious institutions, the microbiological quality of holy water is clearly underinvestigated. We analyzed the microbial load of 54 holy water samples, repeatedly taken in five Roman Catholic churches in the greater area of Villingen-Schwenningen, Germany, by means of aerobic colony counting and Matrix-Assisted Laser Desorption/Ionization (MALDI) Biotyping of representative isolates. Over all samples, colony counting indicated an average aerobic microbial load of 5.85±3.98 × 103 colony forming units (CFU) ml-1 (average± standard error of the mean (SEM)). Urban churches showed significantly higher contaminations than rural churches, probably owing to a greater number of visitors. Out of 145 bacterial isolates, 63 (43%) were identified to genus level and 39 (27%) to species level. The majority of the identified bacteria were typical human skin commensals, mainly affiliated with the genus Staphylococcus. Ten out of 20 (50%) of the identified species were classified as potential pathogens. Appropriate hygiene measures should be taken to control microbial contamination of holy water, e.g., regular water exchange, particularly in highly frequented churches.
High intensity (resistance exercise) training (HIT) defined as a “single set resistance exercise to muscular failure” is an efficient exercise method that allows people with low time budgets to realize an adequate training stimulus. Although there is an ongoing discussion, recent meta-analysis suggests the significant superiority of multiple set (MST) methods for body composition and strength parameters. The aim of this study is to determine whether additional protein supplementation may increase the effect of a HIT-protocol on body composition and strength to an equal MST-level. One hundred and twenty untrained males 30–50 years old were randomly allocated to three groups: (a) HIT, (b) HIT and protein supplementation (HIT&P), and (c) waiting-control (CG) and (after cross-over) high volume/high-intensity-training (HVHIT). HIT was defined as “single set to failure protocol” while HVHIT consistently applied two equal sets. Protein supplementation provided an overall intake of 1.5–1.7 g/kg/d/body mass. Primary study endpoint was lean body mass (LBM). LBM significantly improved in all exercise groups ( p≤0.043 ); however only HIT&P and HVHIT differ significantly from control ( p≤0.002 ). HIT diverges significantly from HIT&P ( p=0.017 ) and nonsignificantly from HVHIT ( p=0.059 ), while no differences were observed for HIT&P versus HVHIT ( p=0.691 ). In conclusion, moderate to high protein supplementation significantly increases the effects of a HIT-protocol on LBM in middle-aged untrained males.
Question - Which classes should i create for my R package?
As package sp is heavily using S4 classes, I would go for S4 classes.
Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients’ mortality. Acid sphingomyelinase (SMPD1)—the principal regulator for rapid and transient generation of the lipid mediator ceramide—is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1+/+ as well as SMPD1−/− animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1−/− littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine.
Question - With a poor performance in ROC curve of the model, does that mean the model is useless at all?
are you sure that the area under the ROC curve is 0. For me that does not make any sense, as non-informative (pure random) model achieves an area of 0.5? I would propose that you re-check those computations.
Question - Is there a commercial device to separate blood bacteria in patients with sepsis for subsequent PCR analysis?
There are more than 8000 rare diseases (RDs) that affect >5 % of the world’s population. Many of the RDs have no effective treatment and lack of knowledge creates delayed diagnosis making management difficult. The emerging concept of the personalized medicine allows for early screening, diagnosis, and individualized treatment of human diseases. In this context, the discovery of biomarkers in RDs will be of prime importance to enable timely prevention and effective treatment. Since 80 % of RDs are of genetic origin, identification of new genes and causative mutations become valuable biomarkers. Furthermore, dynamic markers such as expressed genes, metabolites, and proteins are also very important to follow prognosis and response the therapy. Recent advances in omics technologies and their use in combination can define pathophysiological pathways that can be drug targets. Biomarker discovery and their use in diagnosis in RDs is a major pillar in RD research.
Recently extreme increases in serum creatine-kinase (CK) concentration after initial whole-body electromyostimulation (WB-EMS) were reported that indicating a severe (exertional) rhabdomyolysis. Thus our aim was (1) to verify the reported WB-EMS induced CK-increases, (2) to determine the corresponding consequences for health and (3) to assess physiological CK-adaptation to frequent WB-EMS. Thirty-seven eligible WB-EMS novices and six marathon runners living in the Nürnberg-Erlangen area were included. Trail-I and trial-II determined the effect of one single WB-EMS session to exertion (20 min) on electrolytes, muscular and renal parameters; trial-III evaluated the effect of once a week WB-EMS application for 10 weeks on CK-kinetics. Blood samples of corresponding serum parameters were drawn before, immediately after and 24, 48, 72, and 96 h post WB-EMS exercise. After WB-EMS, serum CK-levels increased by the 96-fold (peak-CK: 23.940 ± 24.545 U/L), 8.5-fold higher compared with CK-increases after a marathon run. However, we did not observe any relevant health consequences with respect to cardiac and renal burdens. Further, following the repeated bout effect, 10 weeks of WB-EMS resulted in a 21-fold reduction of CK-concentration (<1.000 U/l) compared with the baseline test. We confirmed there were exceptionally high CK increases after initial WB-EMS when the intensity was (too) high, but this was ameliorated by a rapid and profound “repeated bout effect” after 10 weeks of WB-EMS application. Although we did not detect any negative consequences in this healthy, well-prepared and medically supervised cohort, initial WB-EMS application to exertion should be strictly avoided in order to prevent hepatic, renal and cardiac incidents.
Question - How to create a set of all possible candidate models automatically using a set of variables? Someone knows a function in R able to do that?
Background Sarcopenic obesity (SO) is characterized by a combination of low muscle and high fat mass with an additive negative effect of both conditions on cardiometabolic risk. The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on the metabolic syndrome (MetS) in community-dwelling women aged ≥70 years with SO. Methods The study was conducted in an ambulatory university setting. Seventy-five community-dwelling women aged ≥70 years with SO living in Northern Bavaria, Germany, were randomly allocated to either 6 months of WB-EMS application with (WB-EMS&P) or without (WB-EMS) dietary supplementation (150 kcal/day, 56% protein) or a non-training control group (CG). WB-EMS included one session of 20 min (85 Hz, 350 μs, 4 s of strain–4 s of rest) per week with moderate-to-high intensity. The primary study endpoint was the MetS Z-score with the components waist circumference (WC), mean arterial pressure (MAP), triglycerides, fasting plasma glucose, and high-density lipoprotein cholesterol (HDL-C); secondary study endpoints were changes in these determining variables. Results MetS Z-score decreased in both groups; however, changes compared with the CG were significant (P=0.001) in the WB-EMS&P group only. On analyzing the components of the MetS, significant positive effects for both WB-EMS groups (P≤0.038) were identified for MAP, while the WB-EMS group significantly differed for WC (P=0.036), and the WB-EMS&P group significantly differed for HDL-C (P=0.006) from the CG. No significant differences were observed between the WB-EMS groups. Conclusion The study clearly confirms the favorable effect of WB-EMS application on the MetS in community-dwelling women aged ≥70 years with SO. However, protein-enriched supplements did not increase effects of WB-EMS alone. In summary, we considered this novel technology an effective and safe method to prevent cardiometabolic risk factors and diseases in older women unable or unwilling to exercise conventionally.
Objective: Multimorbidity related to menopause and/or increased age will put healthcare systems in western nations under ever-greater strain. Effective strategies to prevent diseases are thus of high priority and should be started earlier in life. The purpose of the study was to evaluate the long-term effect of exercise on different important health parameters in initially early postmenopausal women over a 16-year period. Methods: In 1998, 137 early postmenopausal women with osteopenia living in Erlangen-Nürnberg were included in the study. Eighty-six women joined the exercise group (EG) and conducted two supervised group and two home training sessions per week, whereas the control group (CG: n = 51) maintained their physical activity level. Primary outcome parameters were clinical overall fractures incidence; secondary study endpoint was Framingham study-based 10-year risk of coronary death/myocardial infarction and low back pain. Results: In 2014, 59 women of the EG and 46 women of the CG were included in the 16-year follow-up analysis. Framingham study-based 10-year risk of myocardial infarction/coronary death increased significantly (P < 0.001) in both groups; however, changes were significantly more favorable in the EG (5.00% ± 2.94% vs CG: 6.90% ± 3.98%; P = 0.02). The ratio for clinical "overall" fractures was 0.47 (95% CI: 0.24-0.92; P = 0.03), and thus significantly lower in the EG. Although we focused on a high-intensity exercise strategy, low back pain was favorably affected in the EG. Conclusions: Multipurpose exercise programs demonstrated beneficial effects on various relevant risk factors and diseases of menopause or/and increased age, and should thus be preferentially applied for primary or secondary prevention in postmenopausal women.
Background: Time-efficient exercise protocols may encourage subjects to exercise more frequently and could thus be excellent tools for health promotion. The aim of this study was to compare the effectiveness of the time-efficient methods HIT and/versus WB-EMS on cardio-metabolic risk factors in untrained middle-aged males. Methods: Untrained, healthy males (30-50 years) were randomly allocated either to 16-weeks of WB-EMS with 3 applications of 20 min/2 weeks, or 16 weeks of high intensity (resistance) training (HIT) performing 2 sessions/week. Both methods addressed all the main muscle groups. Metabolic-Syndrome Z-Score (MetS-Z-Score), abdominal body fat and total cholesterol/HDL-cholesterol (TC/HDL-C) were defined as the study endpoints. Results: HIT and WB-EMS were similar (p≤.096) effective to improve the MetS-Z-Score (HIT: p=.031 vs. WB-EMS: p=.001) and abdominal body fat (HIT:-4.5±8.1%, p=.014 vs. WB-EMS-4.0±5.2%, p=.002) in this cohort. No significant changes (HIT:-2.7±7.4, p=. 216 vs. WB-EMS:-2.2±10.2 p=.441) or group-differences (p=.931) within and between the groups were determined for TC/HDL-C. Conclusion: WB-EMS and HIT-RT is equally effective, attractive, feasible and time-efficient methods for combatting cardio-metabolic risk factors in untrained middle-aged males. WB-EMS can be considered as an effective option, particularly for subjects with low time resources unwilling or unable to conduct exhausting HIT protocols. The paper's primary contribution is finding that both exercise methods, high intensity resistance training (HIT) as defined as " single-set-to-failure protocol with intensifying strategies " and whole-body electromyostimulation (WB-EMS) are equally effective, attractive and feasible approaches for tackling cardio-metabolic risk factors in untrained middle-aged males with limited time resources.
Question - Why is R changing the class of variables when I import a .csv file?
the standard read functions of R (including read.csv) have also the argument "na.strings" and na.strings = "#NULL!" might also have worked for you.
An interesting alternative is package readr of Hadley Wickham that has function read_csv (not automatically converting strings to factors). It's on CRAN, but see also https://github.com/hadley/readr.
Introduction: The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on sarcopenic obesity (SO) in community-dwelling women more than 70 years with sarcopenic obesity. Methods: Seventy-five community-dwelling women ≥70 years with SO were randomly allocated to either a WB-EMS-application with (WB-EMS &P; 24.9 ± 1.9 kg/m2) or without (WB-EMS; 25.2 ± 1.8 kg/m2) dietary supplementation (150 kcal/day, 56 % protein) or a non-training control group (CG; 24.7 ± 1.4 kg/m2). WB-EMS consisted of one weekly session of 20 min (85 Hz, 350 μs, 4 s of strain-4 s of rest) performed with moderate to high intensity. Primary study endpoint was the Sarcopenia Z-Score constituted by skeletal muscle mass index (SMI, as assessed by dual energy X-ray absorptiometry), grip strength, and gait speed, and secondary study endpoint was body fat (%). Results: Sarcopenia Z-score comparably increases in the WB-EMS and the WB-EMS&P-group (p ≤ .046). Both groups differ significantly (p ≤ .001) from the CG which deteriorated significantly (p = .006). Although body fat changes were most pronounced in the WB-EMS (-0.9 ± 2.1; p = .125) and WB-EMS&P (-1.4 ± 2.5; p = .028), reductions did not statistically differ (p = .746) from the CG (-0.8 ± 2.7; p = .179). Looking behind the covariates, the most prominent changes were determined for SMI, with a significant increase in both EMS-groups (2.0-2.5 %; p ≤ .003) and a decrease in the CG (-1.2 ± 3.1 %; p = .050) with significant between-group differences (p = .001). Conclusion: WB-EMS is a safe and attractive method for increasing muscle mass and functional capacity in this cohort of women 70+ with SO; however, the effect on body fat is minor. Protein-enriched supplements did not increase effects of WB-EMS alone.
- Jun 2016
Background: Only few studies have examined the efficacy of musical intervals on psychological parameters. This study investigated the efficacy of specific musical intervals on mood change.Methods: Volunteers (n = 66) were randomized into three groups. Major seventh, fifth and minor third musical intervals were consecutively played in a randomized order and in different variations for 6 minutes. We used sub-scores of the Basler–Mood-Questionnaire and analyzed and compared pre- and post-differences.Discussion: For “inner balance” there was a statistically significant difference between the third and the seventh (Bonferroni adj. p < 0.001) and the fifth and the seventh (adj. p < 0.001), in both cases with lower “inner balance”-values for the seventh interval. For “vitality” and for “social extroversion” there were statistically significant differences between the third and the fifth, with lower “vitality”-values (adj. p = 0.017) and lower “social extroversion”-values (adj. p = 0.003) for the third in both cases. For “vigilance” there were no differences between the three intervals.Conclusions: Minor third, fifth and major seventh influenced sum scores of the Basler–Mood-Questionnaire in a specific manner. Further research is necessary to clarify the underlaying mechanisms.
Plurality and individuality of hepatocellular carcinoma: PPPM perspectives Krishna Chander Sridhar, Olga Golubnitschaja Department of Radiology, Univeristy of Bonn, Bonn, Germany Correspondence: Olga Golubnitschaja (firstname.lastname@example.org) – Department of Radiology, Univeristy of Bonn, Bonn, Germany The EPMA Journal 2016, 7(Suppl 1):A72 The EPMA Journal 2016, Volume 7 Suppl 1 Page 35 of 42 Keywords: Predictive preventive personalized medicine, Innovative screening methods, Patient-specific therapy, Multilevel diagnostics, Molecular markers, CTCs and CNAPS, Stratification Hepatocellular Carcinoma (HCC) may arise due to various risk fac- tors such as genetic predisposition, chronic hepatic infections, al- coholabuse,hemochromatosis,cirrhosis,obesity,fatty liver disease, etc. [1, 2]. Low mean 5-year survival rate (15 %) and high treatment costs imply the need for more effective treatments tai- lored to the person . The predictive, preventive and personal- ized medicine (PPPM) aims at paradigm change in management of HCC from delayed to advanced approaches creating innovative screening programs, early/predictive diagnostics and targeted therapy . For that, better patient stratification is needed utilizing multilevel diagnostics. Molecular mechanisms which underlie tumor manifestation, progression and aggressiveness may vary substantially inHCC dependingonanumber of factorssuchas localization of the primary tumor, tumor’scharacteristics / sub- type, family history, life-style and co-morbidities. Consequently, a creation of individualized patient profiles is of particular import- ance in patient stratification, predictive/early diagnostics and tar- geted treatments of HCC (see Fig. 4). Further, highly sensitive and specific biomarker-panels play a crucial role in sub-categorization of HCC, e.g. to distinguish between local and distanced metastatic activities, where the latter are functionally linked to circulating en- tities such as circulating tumour cells (CTC) and circulating nucleic acids in plasma and serum (CNAPS) . The integrative PPPM-strategies advancing HCC management (both curative and palliative) may have great impacts on improved screen- ing of individuals at risk, life-quality of targeted patient cohorts, bet- ter healthcare economy and benefits to diagnostic and pharmaceutical industry. References 1. Berliner L, Lemke HU (eds.). An Information Technology Framework for Predictive, Preventive and Personalized Medicine: A Use-Case with Hepato- cellular Carcinoma. In: Advances in Predictive, Preventive and Personalised Medicine, Vol 8in Cham: Springer International Publishing; 2015 2. Fox RK. Surveillance for Hepatocellular Carcinoma. Hepatitis C Online, http:// www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/surveillance- hepatocellular-carcinoma/core-concept/all (2013) Accessed 15 Aug 2015. 3. Thein HH, Isaranuwatchai W, Campitelli MA, Feld JJ, Yoshida E, Sherman M, et al. Healthcare costs associated with hepatocellular carcinoma: a population-based study. Hepatology 2013;58(4):1375-84. 4. Zhao YJ, Ju Q, Li GC. Tumor markers for hepatocellular carcinoma. Mol Clin Oncol. 2013;1(4):593-598.
- Apr 2016
Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address bone. The aims of the present article were to determine the independent effect of exercise frequency (ExFreq) and its corresponding changes on bone mineral density (BMD) and to identify the minimum effective dose that just relevantly affects bone. Based on the 16-year follow-up of the intense, consistently supervised Erlangen Fitness and Osteoporosis Prevention-Study, ExFreq was retrospectively determined in the exercise-group of 55 initially early-postmenopausal females with osteopenia. Linear mixed-effect regression analysis was conducted to determine the independent effect of ExFreq on BMD changes at lumbar spine and total hip. Minimum effective dose of ExFreq based on BMD changes less than the 90% quantile of the sedentary control-group (n=43). Cut-offs were determined after 4, 8, 12 and 16years using bootstrap with 5000 replications. After 16years, average ExFreq ranged between 1.02 and 2.96sessions/week (2.28±0.40sessions/week). ExFreq has an independent effect on LS-BMD (p<.001) and hip-BMD (p=.005) changes. Bootstrap analysis detected a minimum effective dose at about 2sessions/week/16years (cut-off LS-BMD: 2.11, 95% CI: 2.06-2.12; total hip-BMD: 2.22, 95% CI: 2.00-2.78sessions/week/16years). In summary, the minimum effective dose of exercise frequency that relevantly addresses BMD is quite high, at least compared with the low sport participation rate of older adults. This result might not be generalizable across all exercise types, protocols and cohorts, but it does indicate at least that even when applying high impact/high intensity programs, exercise frequency and its maintenance play a key role in bone adaptation.
Question - Best preprocessing methods for imbalanced data in classification algorithms?
There are many different approaches. An interesting option is SMOTE.
Development of a dysregulated immune response discriminates sepsis from uncomplicated infection. Currently used biomarkers fail to describe simultaneously occurring pro- and anti-inflammatory responses potentially amenable to therapy. Marker candidates were screened by microarray and, after transfer to a platform allowing point-of-care testing, validated in a confirmation set of 246 medical and surgical patients. We identified up-regulated pathways reflecting innate effector mechanisms, while down-regulated pathways related to adaptive lymphocyte functions. A panel of markers composed of three up- (Toll-like receptor 5; Protectin; Clusterin) and 4 down-regulated transcripts (Fibrinogen-like 2; Interleukin-7 receptor; Major histocompatibility complex class II, DP alpha1; Carboxypeptidase, vitellogenic-like) described the magnitude of immune alterations. The created gene expression score was significantly greater in patients with definite as well as with possible/probable infection than with no infection (median (Q25/Q75): 80 (60/101)) and 81 (58/97 vs. 49 (27/66), AUC-ROC = 0.812 (95%-CI 0.755–0.869), p < 0.0001). Down-regulated lymphocyte markers were associated with prognosis with good sensitivity but limited specificity. Quantifying systemic inflammation by assessment of both pro- and anti-inflammatory innate and adaptive immune responses provides a novel option to identify patients-at-risk and may facilitate immune interventions in sepsis.
High-intensity (resistance) exercise (HIT) and whole-body electromyostimulation (WB-EMS) are both approaches to realize time-efficient favorable changes of body composition and strength. The purpose of this study was to determine the effectiveness of WB-EMS compared with the gold standard reference HIT, for improving body composition and muscle strength in middle-aged men. Forty-eight healthy untrained men, 30–50 years old, were randomly allocated to either HIT (2 sessions/week) or a WB-EMS group (3 sessions/2 weeks) that exercised for 16 weeks. HIT was applied as “single-set-to-failure protocol,” while WB-EMS was conducted with intermittent stimulation (6 s WB-EMS, 4 s rest; 85 Hz, 350 ms) over 20 minutes. The main outcome parameters were lean body mass (LBM) as determined via dual-energy X-ray absorptiometry and maximum dynamic leg-extensor strength (isokinetic leg-press). LBM changes of both groups (HIT 1.25 ± 1.44% versus WB-EMS 0.93 ± 1.15 %) were significant ( p = . 001 ); however, no significant group differences were detected ( p = . 395 ). Leg-extensor strength also increased in both groups (HIT 12.7 ± 14.7 %, p = . 002 , versus WB-EMS 7.3 ± 10.3 %, p = . 012 ) with no significant ( p = . 215 ) between-group difference. Corresponding changes were also determined for body fat and back-extensor strength. Conclusion . In summary, WB-EMS can be considered as a time-efficient but pricy option to HIT-resistance exercise for people aiming at the improvement of general strength and body composition.
Background: Observational studies have consistently reported severe weight gains during the college years; information about the effect on body composition is scarce, however. Thus, the aim of the study was to determine the effect of exercise changes on body composition during 5 years at university. Methods: Sixty-one randomly selected male and female dental (DES; 21 ± 3 years., 22 ± 2 kg/m(2)) and 53 sport (physical education) students (SPS; 20 ± 2 years., 22 ± 3 kg/m(2)) were accompanied over their 5-year study program. Body mass and body composition as determined via Dual-Energy x-ray-absorptiometry (DXA) at baseline and follow-up were selected as primary study endpoints. Confounding parameters (i.e., nutritional intake, diseases, medication) that may affect study endpoints were determined every two years. Endpoints were log-transformed to stabilize variance and achieve normal distributed values. Paired t-tests and unpaired Welch-t-tests were used to check intra and inter-group differences. Results: Exercise volume decreased significantly by 33% (p < .001) in the DES and increased significantly (p < .001) in the SPS group. Both cohorts comparably (p = .214) gained body mass (SPS: 1.9%, 95%-CI: 0.3-3.5%, p = .019 vs. DES: 3.4%, 1.4-5.5%, p = .001). However, the increase in the SPS group can be completely attributed to changes in LBM (2.3%, 1.1-3.5%, p < 0.001) with no changes of total fat mass (0.6%, -5.0-6.5%, p = 0.823), while DES gained total FM and LBM in a proportion of 2:1. Corresponding changes were determined for appendicular skeletal muscle mass and abdominal body-fat. Maximum aerobic capacity increased (p = .076) in the SPS (1.6%, -0.2-3.3%) and significantly decreased (p = .004) in the DES (-3.3%, -5.4 to -1.2%). Group differences were significant (p < .001). With respect to nutritional intake or physical activity, no relevant changes or group differences were observed. Conclusion: We conclude that the most deleterious effect on fatness and fitness in young college students was the pronounced decreases in exercise volume and particularly exercise intensity. Trial registration: NCT00521235; "Effect of Different Working Conditions on Risk Factors in Dentists Versus Trainers. A Combined Cross sectional and Longitudinal Trial with Student and Senior Employees."; August 24, 2007.
- Jan 2016
Introduction: Sarcopenic obesity (SO) is characterized by the combination of low muscle and high fat mass. Physical exercise may prevent or even restore SO, however, sports participation of most elderly people failed to reach corresponding exercise recommendations. The aim of the study was to determine the effect of time efficient and joint-friendly Whole-Body Electromyostimulation (WB-EMS) on SO in community-dwelling women ≥ 70 years with SO. Material and methods: A randomized controlled trial over 6 months was conducted with community-dwelling women of 70 years and older with SO (skeletal muscle mass index: < 5,75 kg/m2, body-fat > 35 %) living in Erlangen, Germany. 75 eligible women were randomly assigned (1 : 1 : 1) to three study groups (a) WB-EMS (b) WB-EMS and protein-rich supplements (WB-EMS&P) and (c) non-training control (CG). WB-EMS was applied once weekly over 20 min sitting/lying in a supine position using an intermitted EMS-protocol (4 s of EMS, 4 s of rest; 85 Hz, 30 μs, direct impulse-raise) performed with moderate to high intensity. Dietary supplementation consisted of 40 g powder/d (600 kJ) with 56 % protein content (i. e. 22 g/d). Body composition assessments using Dual-Energy x-Ray Absorptiometry (DXA) and functional tests that focussed on the lower limbs (i. e. power and maximum leg strength, chair rising) were conducted. Researchers were blinded with respect to participants' group affiliation. Primary study endpoints were appendicular skeletal muscle mass (ASMM; kg/m2) and body fat mass (kg). Secondary study endpoints were dynamic maximum leg extensor strength, chair rising test and jumping power. Results: Intention-to-treat analysis determined a comparable (p = 0,53) increase of ASMM in both WB-EMS groups (WB-EMS: 2.5 ± 2.7 % and WB-EMS&P: 2.0 ± 2.7 %, p ≤ 0.003) compared to baseline (BL). The WB-EMS groups differed significantly (p < 0.001) from the CG which significantly lost ASMM (1.2 ± 3.3 %, p = 0.050). Body fat mass reductions compared to BL of the WBEMS group (-1.0 ± 2.6; p = 0.121) and WBEMS& P group (-1.4 ± 2.1 %, p = 0.021) were slightly more pronounced compared to the CG (-0.8 ± 2.5 %, p = 0.185), however, these effects remained non-significant (p = 0.628) in between-group comparison. Maximum leg-extensor strength as assessed by an isokinetic leg press, chair rising test and jumping height as determined on a force plate comparably increased in both WBEMS groups (p < 0.001 to 0.008) and maintained in the CG. However, corresponding significant effects between groups were determined only for maximum leg extensor strength (p = 0.002). Conclusion: WB-EMS is a safe and attractive method for increasing muscle mass and functional capacity in this cohort of women ≥ 70 with SO, whereas the effect on body fat is minor. The latter finding, along with the weak results for the more complex chair rising and counter movement jump test, may be referred to the unspecific WB-EMS application. Protein did not increase the effects of WB-EMS, however, the baseline protein consumption was rather high in all subgroups (1.03-1.09 g/kg bodymass/d).
Purpose: High Intensity (resistance exercise) Training (HIT) and Whole-Body Electromyostimulation (WB-EMS) may be the most promising approaches to generate favorable changes of body composition and strength with optimum time-efficiency. In this study, we compared the effect of WB-EMS on Body composition and muscle strength with the “golden standard” HIT over 16 weeks. ››Methods: 30-50 year-old men (n=48) were randomly allocated to a HIT (n=24) with 2 sessions/week of a “single-set-to-failure-protocol” or a WB-EMS-group that exercised 3 sessions in two weeks, using intermittent stimulation (6 sec - 4 sec rest; 85 Hz, 350 ms) over 20 min. An Intention to treat analysis was calculated with Lean Body Mass (LBM) defined as primary endpoint, and appendicular skeletal muscle mass (ASMM), Maximum dynamic leg-extensor and isometric back-extensor strength as secondary endpoints. ››Results: Net exercise time/session was 30.3±2.3 for HIT vs. 20±0 min for WB-EMS (p<.001). LBM (HIT: 1.24±1.40% vs. WB-EMS: 0.91±1.12%) and ASMM (1.92±1.51% vs. WB-EMS: 1.52±1.48%) significantly increased (p≤.003), with no significant group differences (LBM: p=.406 and ASMM: p=.341). In parallel, changes of maximum dynamic leg strength (HIT: 13.5±13.9%, p=.001 vs. WBEMS: 8.0±10.2%, p=.008) and maximum isometric back strength (10.4±9.0%, p<.001 vs. 11.7±9.9%; p<.001) were comparable (p=.332 and p=.609) between groups. Discussion: In conclusion, compared to HIT, WB-EMS can be considered as an even more time-efficient but pricey option for subjects who aim to improve their body composition and general strength.
Background: The aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure. Methods: Patients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4% albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model. Results: Sixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median -68 μmol/L, interquartile range [IQR] -107.5 to -33.5, p = 0.001; SPAD: -59 μmol/L, -84.5 to +36.5, p = 0.001). However, bile acids (MARS: -39 μmol/L, -105.6 to -8.3, p < 0.001; SPAD: -9 μmol/L, -36.9 to +11.4, p = 0.131), creatinine (MARS: -24 μmol/L, -46.5 to -8.0, p < 0.001; SPAD: -2 μmol/L, -9.0 to +7.0/L, p = 0.314) and urea (MARS: -0.9 mmol/L, -1.93 to -0.10, p = 0.024; SPAD: -0.1 mmol/L, -1.0 to +0.68, p = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10%, -0.8 to +20.9%, p < 0.001; SPAD: +7%, -7.5 to +15.5%, p = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD. Conclusions: Both procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation. Trial registration: German Clinical Trials Register ( www.drks.de) DRKS00000371. Registered 8 April 2010.
Question - How can I associate specific colors to specific data for the color bar in heatmaps in R?
I would propose to switch to the Bioconductor package ComplexHeatmap; see http://www.bioconductor.org/packages/release/bioc/html/ComplexHeatmap.html
There are a lot of examples in the documentation; e.g. adding annotations is explained in
Question - How do I fit the beta-binomial regression. Please I need assistance with beta-binomial regression using R or STATA.?
Concentration and distribution of individual endogenous ceramide species is crucial for apoptosis induction in response to various stimuli. Exogenous ceramide analogs induce apoptosis and can in turn modify the composition/concentrations of endogenous ceramide species and associated signaling. In this study, we show here that the elevation of endogenous C16-ceramide levels is a common feature of several known apoptosis-inducing triggers like mmLDL, TNF-alpha, H2O2 and exogenous C6-ceramide. Vice versa apoptosis requires elevation of endogenous C16-ceramide levels in cells. Enantiomers of a synthetic ceramide analog HPL-1RS36N have been developed as probes and vary in their capacity to inducing apoptosis in macrophages and HT-29 cells. Apoptosis induction by the two synthetic ceramide analogs HPL-39N and HPL-1R36N correlates with generation of cellular C16-ceramide concentration. In contrast to the S-enantiomer HPL-1S36N, the R-enantiomer HPL-1R36N shows significant effects on the expression of distinct genes known to be involved in cell cycle, cell growth and cell death (CXCL10, CCL5 and TNF-alpha), similarly on apoptosis induction. Enantioselective effects on transcription induced by metabolically stable synthetic probes provide clues on molecular mechanisms of ceramide-induced signaling, as well as leads for future anti-cancer agents.
Question - Is it possible to get a classifier with a fixed sensitivity ?
ACC has several drawbacks eg. you should be careful in case of class imbalance. Anyway, the figure (ROC curve) in my view is the better alternative to present the performance instead of giving just one number.
All co-authors (50)