Reference catalogue for ICT services in healthcare : model for ICT service management, controlling and benchmarking : version 1.0

Translation of the German original

Polysilicon vs. Aluminum Gate PMOS Ring Oscillators

A nine stage PMOS ring oscillator was designed using polysilicon gates for a self-aligning process while another was designed using a standard metal gate process. A comparison of the polysilicon and metal gate PMQS processes was planned to show the reduced gate capacitance of the self-aligning process. This reduced gate capacitance was to be observed by measuring and comparing the propagation delay of each design on the oscilloscope

Inferring Dynamic Signatures of Microbes in Complex Host Ecosystems

The human gut microbiota comprise a complex and dynamic ecosystem that profoundly affects host development and physiology. Standard approaches for analyzing time-series data of the microbiota involve computation of measures of ecological community diversity at each time-point, or measures of dissimilarity between pairs of time-points. Although these approaches, which treat data as static snapshots of microbial communities, can identify shifts in overall community structure, they fail to capture the dynamic properties of individual members of the microbiota and their contributions to the underlying time-varying behavior of host ecosystems. To address the limitations of current methods, we present a computational framework that uses continuous-time dynamical models coupled with Bayesian dimensionality adaptation methods to identify time-dependent signatures of individual microbial taxa within a host as well as across multiple hosts. We apply our framework to a publicly available dataset of 16S rRNA gene sequences from stool samples collected over ten months from multiple human subjects, each of whom received repeated courses of oral antibiotics. Using new diversity measures enabled by our framework, we discover groups of both phylogenetically close and distant bacterial taxa that exhibit consensus responses to antibiotic exposure across multiple human subjects. These consensus responses reveal a timeline for equilibration of sub-communities of micro-organisms with distinct physiologies, yielding insights into the successive changes that occur in microbial populations in the human gut after antibiotic treatments. Additionally, our framework leverages microbial signatures shared among human subjects to automatically design optimal experiments to interrogate dynamic properties of the microbiota in new studies. Overall, our approach provides a powerful, general-purpose framework for understanding the dynamic behaviors of complex microbial ecosystems, which we believe will prove instrumental for future studies in this field

Computational discovery of gene modules, regulatory networks and expression programs

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2007.Includes bibliographical references (p. 163-181).High-throughput molecular data are revolutionizing biology by providing massive amounts of information about gene expression and regulation. Such information is applicable both to furthering our understanding of fundamental biology and to developing new diagnostic and treatment approaches for diseases. However, novel mathematical methods are needed for extracting biological knowledge from high-dimensional, complex and noisy data sources. In this thesis, I develop and apply three novel computational approaches for this task. The common theme of these approaches is that they seek to discover meaningful groups of genes, which confer robustness to noise and compress complex information into interpretable models. I first present the GRAM algorithm, which fuses information from genome-wide expression and in vivo transcription factor-DNA binding data to discover regulatory networks of gene modules. I use the GRAM algorithm to discover regulatory networks in Saccharomyces cerevisiae, including rich media, rapamycin, and cell-cycle module networks. I use functional annotation databases, independent biological experiments and DNA-motif information to validate the discovered networks, and to show that they yield new biological insights. Second, I present GeneProgram, a framework based on Hierarchical Dirichlet Processes, which uses large compendia of mammalian expression data to simultaneously organize genes into overlapping programs and tissues into groups to produce maps of expression programs. I demonstrate that GeneProgram outperforms several popular analysis methods, and using mouse and human expression data, show that it automatically constructs a comprehensive, body-wide map of inter-species expression programs.(cont.) Finally, I present an extension of GeneProgram that models temporal dynamics. I apply the algorithm to a compendium of short time-series gene expression experiments in which human cells were exposed to various infectious agents. I show that discovered expression programs exhibit temporal pattern usage differences corresponding to classes of host cells and infectious agents, and describe several programs that implicate surprising signaling pathways and receptor types in human responses to infection.by Georg Kurt Gerber.Ph.D

The Relationship between Myoglobin, Aerobic Capacity, Nitric Oxide Synthase Activity and Mitochondrial Function in Fish Hearts

The dynamic interactions between nitric oxide (NO) and myoglobin (Mb) in the cardiovascular system have received considerable attention. The loss of Mb, the principal O2 carrier and a NO scavenger/producer, in the heart of some red-blooded fishes provides a unique opportunity for assessing this globin’s role in NO homeostasis and mitochondrial function. We measured Mb content, activities of enzymes of NO and aerobic metabolism [NO Synthase (NOS) and citrate synthase, respectively] and mitochondrial parameters [Complex-I and -I+II respiration, coupling efficiency, reactive oxygen species production/release rates and mitochondrial sensitivity to inhibition by NO (i.e., NO IC50)] in the heart of three species of red-blooded fish. The expression of Mb correlated positively with NOS activity and NO IC50, with low NOS activity and a reduced NO IC50 in the Mb-lacking lumpfish (Cyclopterus lumpus) as compared to the Mb-expressing Atlantic salmon (Salmo salar) and short-horned sculpin (Myoxocephalus scorpius). Collectively, our data show that NO levels are fine-tuned so that NO homeostasis and mitochondrial function are preserved; indicate that compensatory mechanisms are in place to tightly regulate [NO] and mitochondrial function in a species without Mb; and strongly suggest that the NO IC50 for oxidative phosphorylation is closely related to a fish’s hypoxia tolerance

Prevalence of Stunting and Relationship between Stunting and Associated Risk Factors with Academic Achievement and Cognitive Function: A Cross-Sectional Study with South African Primary School Children

Childhood stunting can have negative long-term consequences on cognitive development, academic achievement, and economic productivity later in life. We determined the prevalence of stunting and examined whether stunting and associated risk factors (low dietary diversity, insufficient hemoglobin, food insecurity, and soil-transmitted helminth (STH) infections) are associated with academic achievement and cognitive function among South African children living in marginalized communities. A cross-sectional sample of 1277 children (aged 5-12 years) was analyzed. Stunting was defined according to 2007 WHO growth references. Cognitive functioning was measured with the computerized Flanker task and academic performance via school grades. Blood and stool samples were collected to obtain hemoglobin level and STH infection. Dietary diversity was assessed by a food frequency questionnaire. Associations were examined via mixed linear regression (with school class as a random intercept). Nine percent of the children were stunted (95% CI: 7.6-10.8%). Low dietary diversity (β = 0.13,; p; = 0.004), food insecurity (β = -0.12,; p; = 0.034), and stunting (β = -0.13,; p; = 0.031) were associated with poorer end of the year results among girls. No such associations were found among boys. No significant associations were found for socioeconomic status and hemoglobin levels. The prevalence of stunting and STH infections were low in the present sample. Risk factors seem differently associated with girls' and boys' academic achievement. Promoting nutrition may help to promote academic achievement among girls living in low- and middle-income countries

Is the PHQ-9 a Unidimensional Measure of Depression? A 58,272-Participant Study

The PHQ-9 has become a measure of reference in depression research and clinical practice. However, the issue of the PHQ-9’s unidimensionality has not been fully elucidated, and the usability of the PHQ-9’s total score requires clarification. In this study, we examined the dimensionality, scalability, and monotonicity properties of the PHQ-9 as well as the scale’s total-score reliability. We did so based on exploratory structural equation modeling (ESEM) bifactor analysis and Mokken scale analysis (MSA). We relied on a total of 58,272 participants (63% female; Mage = 43, SDage = 13) from 29 samples involving seven different countries (e.g., Germany, the U.S.) and five different languages (e.g., German, English). We found no concerning deviations from measurement invariance for our ESEM bifactor model, neither across samples nor across sexes, age groups, and languages. The PHQ-9 met the requirements for essential unidimensionality in the pooled sample and across sex-, age-, and language-based subsamples. In each case, the general factor was strong (e.g., factor loadings ranged from 0.725 to 0.893 in the pooled sample) and Omega Hierarchical values exceeded 0.900. The correlations between the general factor and the observed total scores were large (≥ 0.952). Our MSA, including multilevel MSA, revealed that the PHQ-9’s scalability is satisfactory. No monotonicity violation was detected, suggesting that the scale’s total score accurately orders respondents on the latent Depression variable. Total-score reliability was good. This study provides robust evidence that the PHQ-9 can be used as a unidimensional measure of depressive symptoms by researchers and practitioners

Associations of growth impairment and body composition among South African school-aged children enrolled in the KaziAfya project

(1) Background: Early childhood malnutrition may result in increased fat mass (FM) among school-aged children in low- and middle-income countries (LMICs). We explored whether South African children with shorter stature have greater overall and abdominal FM compared to normal stature children. (2) Methods: Baseline assessments of body composition and weight were determined among school-aged children enrolled in a randomized controlled trial in Port Elizabeth, South Africa, using bioelectrical impedance analysis. Multiple linear regression models tested associations of children's height and degree of stunting with FM, fat free mass (FFM), truncal fat mass (TrFM), and truncal fat free mass (TrFFM) overall and by sex. (3) Results: A total of 1287 children (619 girls, 668 boys) were assessed at baseline. Reduced child height was associated with higher FM and lower FFM and TrFFM, but these associations were reversed with increases in height. Girls classified as mildly or moderately/severely stunted had higher FM and TrFM but lower FFM and TrFFM, while no association was found for boys. (4) Conclusions: Our study suggests that efforts to reduce the non-communicable disease burden in LMICs should target growth-impaired children who may have greater overall FM and greater abdominal FM

Evaluation of a Physical Activity and Multi-Micronutrient Intervention on Cognitive and Academic Performance in South African Primary Schoolchildren

Executive functions (EFs) are essential for optimal academic development. Appropriate nutrition and physical activity (PA) have been shown to facilitate optimal cognitive development. Therefore, this study examined whether a 12-week school-based PA and multi-micronutrient supplementation (MMNS) intervention would improve cognitive and academic performance. A cluster-randomized controlled trial (RCT) was conducted. Children from four schools located in a peri-urban area of South Africa were randomly assigned to (i) PA + MMNS, (ii) PA + placebo, (iii) MMNS or (iv) placebo. Information processing and inhibitory control were measured with a computerized Flanker task. End-of-year results provided insight into academic achievement. Anthropometric measures were used to determine nutritional status. Data were analyzed with linear mixed-models, adjusting for baseline scores, school classes and age; 932 children (458 girls (49.1 completed baseline and post-intervention assessments. Cognitive performance improved among all four groups, with no significant group x time effects. For academic achievement, there was no significant interaction effect between the combined intervention group and placebo. We encourage future studies in this neglected area in order to determine the most optimal design of school-based nutrition and PA programs to enhance overall cognitive performance