Editorial: choosing new targets for rheumatoid arthritis therapeutics: too interesting to fail?

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Coupled thermodynamic and biologic modelling of Legionella pneumophila proliferation in domestic hot water systems

The production of Domestic Hot Water (DHW) dominates the total energy demand. One of the main reasons for the high energy demand is that DHW is stored and distributed at temperatures above 55°C to mitigate the risk of infecting the DHW system with Legionella Pneumophila. At these temperatures, Legionella bacteria are effectively killed. For most of the applications of DHW, temperatures of only 30-40°C are required. This disparity (between 55 and 30-40°C) doubles the temperature difference between the DHW system and the environment and has a detrimental effect on the efficiency of DHW production units. A simulation model will be developed that allows to investigate the infection risk for Legionella in the design phase of a DHW system and to test the effectiveness of disinfection techniques on an infected system. In addition to the modeling work, a test rig will be built and the relevant temperature and use profiles will be measured in DHW systems of several buildings. With the thermodynamically validated model, the Legionella infection risk of 5 to 10 DHW system configurations will be assessed and new design guidelines will be proposed based on an optimization study that looks for the trade-off between infection risk and energy efficiency

Technologies and combination therapies for enhancing movement training for people with a disability

There has been a dramatic increase over the last decade in research on technologies for enhancing movement training and exercise for people with a disability. This paper reviews some of the recent developments in this area, using examples from a National Science Foundation initiated study of mobility research projects in Europe to illustrate important themes and key directions for future research. This paper also reviews several recent studies aimed at combining movement training with plasticity or regeneration therapies, again drawing in part from European research examples. Such combination therapies will likely involve complex interactions with motor training that must be understood in order to achieve the goal of eliminating severe motor impairment

Interpreting Metabolomic Profiles using Unbiased Pathway Models

Human disease is heterogeneous, with similar disease phenotypes resulting from distinct combinations of genetic and environmental factors. Small-molecule profiling can address disease heterogeneity by evaluating the underlying biologic state of individuals through non-invasive interrogation of plasma metabolite levels. We analyzed metabolite profiles from an oral glucose tolerance test (OGTT) in 50 individuals, 25 with normal (NGT) and 25 with impaired glucose tolerance (IGT). Our focus was to elucidate underlying biologic processes. Although we initially found little overlap between changed metabolites and preconceived definitions of metabolic pathways, the use of unbiased network approaches identified significant concerted changes. Specifically, we derived a metabolic network with edges drawn between reactant and product nodes in individual reactions and between all substrates of individual enzymes and transporters. We searched for “active modules”—regions of the metabolic network enriched for changes in metabolite levels. Active modules identified relationships among changed metabolites and highlighted the importance of specific solute carriers in metabolite profiles. Furthermore, hierarchical clustering and principal component analysis demonstrated that changed metabolites in OGTT naturally grouped according to the activities of the System A and L amino acid transporters, the osmolyte carrier SLC6A12, and the mitochondrial aspartate-glutamate transporter SLC25A13. Comparison between NGT and IGT groups supported blunted glucose- and/or insulin-stimulated activities in the IGT group. Using unbiased pathway models, we offer evidence supporting the important role of solute carriers in the physiologic response to glucose challenge and conclude that carrier activities are reflected in individual metabolite profiles of perturbation experiments. Given the involvement of transporters in human disease, metabolite profiling may contribute to improved disease classification via the interrogation of specific transporter activities

The Paradata Information Model

Presentation at the North American Data Documentation Conference (NADDI) 2013Paradata is data on study processes and the collection of study data. Here we describe the development of a Paradata Information Model (PIM) in support of the National Children¹s Study (NCS) of the Eunice Kennedy Shriver National Institute of Child Health and Development. We propose that paradata can be recorded with accompanying metadata informed by the General Longitudinal Business Process Model (GLBPM) developed by the Data Documentation Initiative (DDI) and the General Statistical Business Process Model (GSBPM). The PIM is be constructed in a joint top-down and bottom-up approach, appropriating broad verbs from DDI, HL7, LS-DAM, and CDISC, while incorporating study-specific processes involved in collecting NCS operational data elements (ODEs). The hope of paradata in longitudinal studies is that the collection of paradata will ensure that future researchers can integrate disparate data sets collected by a variety of technologies, especially in rapidly-evolving fields like genomics. Additionally, by giving PIM elements preconditions and postconditions, we can develop software agents which use paradata metadata as well as other information to assist humans in conducting biomedical research, ultimately facilitating more rapid collection and analysis of information and enabling a broader subset of researchers to discover and extract relevant information from study data sets.Institute for Policy & Social Research, University of Kansas; University of Kansas Libraries; Alfred P. Sloan Foundation; Data Documentation Initiative Alliance, Booz Allen Hamilto