Reliability of 3D laser-based anthropometry and comparison with classical anthropometry

Anthropometric quantities are widely used in epidemiologic research as possible confounders, risk factors, or outcomes. 3D laser-based body scans (BS) allow evaluation of dozens of quantities in short time with minimal physical contact between observers and probands. The aim of this study was to compare BS with classical manual anthropometric (CA) assessments with respect to feasibility, reliability, and validity. We performed a study on 108 individuals with multiple measurements of BS and CA to estimate intra- and inter-rater reliabilities for both. We suggested BS equivalents of CA measurements and determined validity of BS considering CA the gold standard. Throughout the study, the overall concordance correlation coefficient (OCCC) was chosen as indicator of agreement. BS was slightly more time consuming but better accepted than CA. For CA, OCCCs for intra- and inter-rater reliability were greater than 0.8 for all nine quantities studied. For BS, 9 of 154 quantities showed reliabilities below 0.7. BS proxies for CA measurements showed good agreement (minimum OCCC > 0.77) after offset correction. Thigh length showed higher reliability in BS while upper arm length showed higher reliability in CA. Except for these issues, reliabilities of CA measurements and their BS equivalents were comparable

Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia

Background: Community-acquired pneumonia (CAP) is an acute disease condition with a high risk of rapid deteriorations. We analysed the influence of genetics on cytokine regulation to obtain a better understanding of patient’s heterogeneity. Methods: For up to N = 389 genotyped participants of the PROGRESS study of hospitalised CAP patients, we performed a genome-wide association study of ten cytokines IL-1β, IL-6, IL-8, IL-10, IL-12, MCP-1 (MCAF), MIP-1α (CCL3), VEGF, VCAM-1, and ICAM-1. Consecutive secondary analyses were performed to identify independent hits and corresponding causal variants. Results: 102 SNPs from 14 loci showed genome-wide significant associations with five of the cytokines. The most interesting associations were found at 6p21.1 for VEGF (p = 1.58 × 10−20), at 17q21.32 (p = 1.51 × 10−9) and at 10p12.1 (p = 2.76 × 10−9) for IL-1β, at 10p13 for MIP-1α (CCL3) (p = 2.28 × 10−9), and at 9q34.12 for IL-10 (p = 4.52 × 10−8). Functionally plausible genes could be assigned to the majority of loci including genes involved in cytokine secretion, granulocyte function, and cilial kinetics. Conclusion: This is the first context-specific genetic association study of blood cytokine concentrations in CAP patients revealing numerous biologically plausible candidate genes. Two of the loci were also associated with atherosclerosis with probable common or consecutive pathomechanisms

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.Peer reviewe

Lasergestützte 3D-Anthropometrie - Von der Epidemiologie zur Genetik

In der Epidemiologie spielen Körpermaße eine wichtige Rolle als Indikatoren für häufig vorkommende Zivilisationskrankheiten wie zum Beispiel Herz-Kreislauf-Erkrankungen oder Diabetes. Die Vermessung von Hand ist dabei als Goldstandard etabliert. Betrachtet werden häufig Körpergröße, Körpergewicht, Oberarmlänge, Oberarmumfang, Taillenumfang, Hüftumfang, Oberschenkellänge, Oberschenkelumfang und Wadenumfang. Für viele dieser Maße beziehungsweise davon abgeleiteter Größen existieren bereits genomweite Assoziationsstudien, wie zum Beispiel innerhalb des GIANT-Konsortiums zu Körpergröße, Body Mass Index und Taille, Hüfte und Taille-Hüfte-Verhältnis. Ziel dieser Arbeit war es, die 3D-Anthropometrie über den Körper-Scanner als neue Messmethode zu etablieren. Dazu stand das ANTHROSCAN VITUS XXL SYSTEM, bestehend aus dem Körper-Scanner VITUS XXL und der Software ANTHROSCAN BASIS von dem Unternehmen Human Solutions zur Verfügung. Die Körper-Scanner-Software bestimmt gemäß DIN EN ISO 20685 standardmäßig über 150 Maße mit der Möglichkeit der Hinzunahme weiterer Körpermaße. Das Hauptaugenmerk lag auf der Untersuchung der Messgenauigkeit der neuen Körper-Scanner-Methode. Dies beinhaltete zunächst die Analyse der Übereinstimmung von Mehrfachmessungen durch den Körper-Scanner. Dazu wurden sowohl Intra-Beobachter-Reliabilitäten als auch Inter-Beobachter-Reliabilitäten bestimmt. Zur Quantifizierung der Konkordanz wurde der Overall Concordance Correlation Coefficient verwendet. Diese Ergebnisse wurden mit denen aus der klassischen Anthropometrie verglichen. Für beide Messmethoden konnten dabei – bis auf wenige Ausnahmen für die 3D-Anthropometrie – sehr gute Ergebnisse ermittelt werden. Im Anschluss daran erfolgt die Untersuchung der Validität, das heißt der Vergleich der manuellen mit der automatisierten Messung. Die Konkordanz wurde ebenfalls über den Overall Concordance Correlation Coefficient bestimmt. Die resultierenden Übereinstimmungen liegen alle im guten bis sehr guten Bereich. Darauf aufbauend wurde untersucht, wie gut sich aus den bestehenden Körper-Scanner-Maßen Derivate bilden lassen. Dies wurde am Beispiel der Körperoberfläche als zweidimensionales Objekt analysiert. Dabei erfolgten zunächst auch wieder Reliabilitätsuntersuchungen bezüglich Intra-Beobachter-Reliabilität und Inter-Beobachter-Reliabilität. Die berechneten Werte gemäß Overall Concordance Correlation Coefficient lagen beide im sehr guten Bereich. Zur Bestimmung der Körperoberfläche werden im Alltag empirische Formeln zur Schätzung der Körperoberfläche über Körpergröße und Körpergewicht herangezogen. Dementsprechend wurde, unter der Annahme der validen Bestimmung der Körperoberfläche über den Körper-Scanner, diese tatsächliche Oberfläche mit der geschätzten Oberfläche aus den empirischen Formeln verglichen. Die Ergebnisse waren überraschend gut. Insgesamt hervorzuheben sind die Formeln nach Fujimoto & Watanabe, Shuter & Aslani und Sendroy & Cecchini. Dennoch war es über Reparametrisierung mit den vorliegenden Daten möglich, eine Verbesserung der Oberflächenschätzung durch empirische Formeln mit Körpergröße und Körpergewicht zu erreichen. Entsprechende Formeln wurden entsprechend zur weiteren Anwendung vorgeschlagen. Da die Bestimmung von Körpermaßen durch die händische Vermessung bisher nur auf einige wenige Maße beschränkt war, existieren folglich auch nur für diese Phänotypen Resultate aus genetischen Assoziationsanalysen. Dies betrifft vor allem die Körpergröße, den Body Mass Index und das Taille-Hüfte-Verhältnis. Durch Ermittlung von mehr als dem Zehnfachen der bisher üblichen Maße, können nun auch genomweite Assoziationsstudien bezüglich dieser Körpermaße durchgeführt werden. Dies erfolgte hier für die über 150 Körpermaße der knapp 7.500 vermessenen und genotypisierten LIFE-Adult-Probanden. Zunächst wurden die Daten hinsichtlich ihrer Korrelationsstruktur analysiert. Jeder Proband lässt sich über die etwa 150 Maße charakterisieren, welche jedoch Korrelationen untereinander aufweisen. Dementsprechend war es erforderlich, diese Korrelationsstruktur zu untersuchen und gegebenenfalls eine Dimensionsreduktion beziehungsweise eine Einteilung in Gruppen von Körpermaßen vorzunehmen. Es zeigte sich, dass sich die knapp 150 Körpermaße in weniger als zehn Gruppen zusammenfassen lassen. Auf der Suche nach einem Referenzmaß für jede Gruppe fiel auf, dass bisher im Rahmen der klassischen Anthropometrie nicht betrachtete Maße eine beachtenswerte Rolle spielen. Dazu zählen Abstand Taillenband zur Taille, Höhe Taille, Schulterbreite aber auch Armumfang, Armdurchmesser, Beinumfang und beispielsweise Schrittlänge. Im Rahmen der genomweiten Assoziationsanalyse wurden in dieser Arbeit einige ausgewählte Resultate derjenigen Körpermaße der 3D-Anthropometrie präsentiert, für welche es ein passendes Äquivalent in der klassischen Anthropometrie gibt. Dabei konnten genomweit signifikante Assoziationen für Körpergröße, Oberarmlänge und Oberarmumfang festgestellt werden.:1. Einführung 1.1 Bedeutung der Anthropometrie 1.2 Klassische Messung und 3D-Körper-Scanner 1.3 Fragestellung der Arbeit 2. Validität, Reliabilität und Akzeptanz der automatisierten und klassischen Messung bei Erwachsenen und Kindern 3. Möglichkeit der Ableitung weiterer Größen aus dem 3D-Körper-Scan am Beispiel der Körperoberfläche 4. Genomweite Assoziationsanalyse bezüglich 3D-Körper-Scanner-Maßen 4.1 Warum noch eine GWAS zu Körpermaßen? 4.2 Welche Daten stehen zur Verfügung? 4.3 Vorbereitungen der GWAS 4.3.1 Fallzahl, Datenvollständigkeit und Ausreißer 4.3.2 Korrelation zwischen den Merkmalen 4.3.3 Hauptkomponentenanalyse 4.3.4 Partielle Kleinste-Quadrate-Methode (Diskriminanzanalyse) 4.3.5 Cluster-Verfahren 1: k-Means-Clustering 4.3.6 Clusterverfahren 2: Hierarchische Cluster-Analyse 4.3.7 Vergleich 4.4 Was genau passiert bei einer GWAS? 4.4.1 Qualitätskontrolle 4.4.2 Imputation 4.4.3 Statistische Tests 4.5 Ergebnisse der GWAS 5. Zusammenfassung Literaturverzeichnis Abbildungsverzeichnis Darstellung des eigenen Beitrags Selbstständigkeitserklärung Lebenslauf Publikationen Danksagun

The reliability of a restraint sensor system for the computer-supported detection of spinal stabilizing muscle deficiencies

Background: The presence of muscular deficiency seems to be a major cause of back pain that requires counteractions. Considering that the autochthonous back muscles, responsible for straightening and stabilizing the spine, cannot be activated voluntarily, they can be strengthened only through specific training. The computer-supported test and training system (CTT) Centaur (BfMC GmbH, Leipzig, SN, Germany) seems well suited for this purpose. To show its potential as a reliable diagnostic and training tool, this study aimed to evaluate the test-retest reliability of this 3D spatial rotation device. Methods: A prospective pilot study was conducted in 20 healthy volunteers of both sexes. For test-retest reliability analysis, three measurements were performed with a two-day interval between each measurement. Each measurement consisted of a one-minute endurance test performed in eight different positions (transverse plane). During the test, the subject was tilted by 90° in the sagittal plane from a neutral, upright position. Meanwhile, the subject's level of upper body stabilization along the body axis was assessed. All trunk movements (momentum values) were quantified by a multicomponent force sensor and standardized relative to the subject's upper body mass. The range of motion was assessed by 95% confidence ellipse analysis. Here, all position-specific confidence ellipses for each measurement were merged to a summarized quantity. Finally, ICC analysis using a single-rating, absolute agreement, two-way mixed-effects model and a Bland-Altman plot was performed to determine the reliability. Results: Considering all measurements (t1, t2, t3), the ICC for reliability evaluation was 0.805, and the corresponding 95% confidence interval (CI) was [0.643, 0.910]. Moreover, the Bland-Altman plots for all three pairs of time points did not show significant differences. Conclusion: This study concludes that the CTT Centaur shows good test-retest reliability, indicating it can be used in clinical practice in the future

The reliability of a restraint sensor system for the computer-supported detection of spinal stabilizing muscle deficiencies

Background: The presence of muscular deficiency seems to be a major cause of back pain that requires counteractions. Considering that the autochthonous back muscles, responsible for straightening and stabilizing the spine, cannot be activated voluntarily, they can be strengthened only through specific training. The computer-supported test and training system (CTT) Centaur (BfMC GmbH, Leipzig, SN, Germany) seems well suited for this purpose. To show its potential as a reliable diagnostic and training tool, this study aimed to evaluate the test-retest reliability of this 3D spatial rotation device. Methods: A prospective pilot study was conducted in 20 healthy volunteers of both sexes. For test-retest reliability analysis, three measurements were performed with a two-day interval between each measurement. Each measurement consisted of a one-minute endurance test performed in eight different positions (transverse plane). During the test, the subject was tilted by 90° in the sagittal plane from a neutral, upright position. Meanwhile, the subject's level of upper body stabilization along the body axis was assessed. All trunk movements (momentum values) were quantified by a multicomponent force sensor and standardized relative to the subject's upper body mass. The range of motion was assessed by 95% confidence ellipse analysis. Here, all position-specific confidence ellipses for each measurement were merged to a summarized quantity. Finally, ICC analysis using a single-rating, absolute agreement, two-way mixed-effects model and a Bland-Altman plot was performed to determine the reliability. Results: Considering all measurements (t1, t2, t3), the ICC for reliability evaluation was 0.805, and the corresponding 95% confidence interval (CI) was [0.643, 0.910]. Moreover, the Bland-Altman plots for all three pairs of time points did not show significant differences. Conclusion: This study concludes that the CTT Centaur shows good test-retest reliability, indicating it can be used in clinical practice in the future

Automated Complete Blood Cell Count Using Sysmex XN-9000® in the Diagnosis of Newborn Infection

The early identification of septically infected newborn infants is important for ensuring good outcomes. Blood cell differentiations are helpful, but they are often time consuming and inaccurate. In this study, we evaluated the use of automatic white blood cell differentiations by flow cytometry for the diagnosis of neonatal sepsis. Episodes of suspected infection in neonates were retrospectively classified into two groups, unlikely infection (UI, levels of Interleukin-6 < 400 pg/mL or CRP within 48 h < 10 mg/L), n = 101 and probable infection (PI, Interleukin-6 ≥ 400 pg/mL or CRP within 48 h ≥ 10 mg/L), n = 98. Complete blood cell counts were performed by Sysmex XN-9000® using flow cytometry. Relative and absolute proportions of immature granulocytes were evaluated. Unexpectedly, the absolute count of immature granulocytes was significantly lower in the group of PI compared to UI neonates. Similar results were found when analysing the relative proportion of immature granulocytes among all neutrophil granulocytes. On the other hand, manually counted immature to total (I/T) ratios of granulocytes were higher in PI than in UI infants. Therefore, we conclude that differentiations of granulocytes by Sysmex XN-9000® can be used to distinguish between infected and uninfected neonates if the results are interpreted according to our findings. A low count of immature granulocytes as determined by Sysmex XN-9000® may indicate neonatal infection

Automated Complete Blood Cell Count Using Sysmex XN-9000® in the Diagnosis of Newborn Infection

The early identification of septically infected newborn infants is important for ensuring good outcomes. Blood cell differentiations are helpful, but they are often time consuming and inaccurate. In this study, we evaluated the use of automatic white blood cell differentiations by flow cytometry for the diagnosis of neonatal sepsis. Episodes of suspected infection in neonates were retrospectively classified into two groups, unlikely infection (UI, levels of Interleukin-6 < 400 pg/mL or CRP within 48 h < 10 mg/L), n = 101 and probable infection (PI, Interleukin-6 ≥ 400 pg/mL or CRP within 48 h ≥ 10 mg/L), n = 98. Complete blood cell counts were performed by Sysmex XN-9000® using flow cytometry. Relative and absolute proportions of immature granulocytes were evaluated. Unexpectedly, the absolute count of immature granulocytes was significantly lower in the group of PI compared to UI neonates. Similar results were found when analysing the relative proportion of immature granulocytes among all neutrophil granulocytes. On the other hand, manually counted immature to total (I/T) ratios of granulocytes were higher in PI than in UI infants. Therefore, we conclude that differentiations of granulocytes by Sysmex XN-9000® can be used to distinguish between infected and uninfected neonates if the results are interpreted according to our findings. A low count of immature granulocytes as determined by Sysmex XN-9000® may indicate neonatal infection