Mapping of UK Biobank clinical codes: Challenges and possible solutions.

OBJECTIVE: The UK Biobank provides a rich collection of longitudinal clinical data coming from different healthcare providers and sources in England, Wales, and Scotland. Although extremely valuable and available to a wide research community, the heterogeneous dataset contains inconsistent medical terminology that is either aligned to several ontologies within the same category or unprocessed. To make these data useful to a research community, data cleaning, curation, and standardization are needed. Significant efforts to perform data reformatting, mapping to any selected ontologies (such as SNOMED-CT) and harmonization are required from any data user to integrate UK Biobank hospital inpatient and self-reported data, data from various registers with primary care (GP) data. The integrated clinical data would provide a more comprehensive picture of one's medical history. MATERIALS AND METHODS: We evaluated several approaches to map GP clinical Read codes to International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) terminologies. The results were compared, mapping inconsistencies were flagged, a quality category was assigned to each mapping to evaluate overall mapping quality. RESULTS: We propose a curation and data integration pipeline for harmonizing diagnosis. We also report challenges identified in mapping Read codes from UK Biobank GP tables to ICD and SNOMED CT. DISCUSSION AND CONCLUSION: Some of the challenges-the lack of precise one-to-one mapping between ontologies or the need for additional ontology to fully map terms-are general reflecting trade-offs to be made at different steps. Other challenges are due to automatic mapping and can be overcome by leveraging existing mappings, supplemented with automated and manual curation.

In-cell protein dynamics.

The native intracellular environment of proteins is crowded with metabolites and macromolecules. However, most biophysical information concerning proteins is acquired in dilute solution. To determine whether there are differences in dynamics, nuclear magnetic resonance spectroscopy can be used to measure 15N relaxation in uniformly 15N-enriched apocytochrome b5 inside living Escherichia coli and in dilute solution. Such data can then be used to compare the fast backbone dynamics of the partially folded protein in cells to its dynamics in dilute solution by using Lipari-Szabo analysis. It appears that the intracellular environment does not alter the protein's structure, or significantly change its fast dynamics. Specifically, the cytosol does not change the amplitude of fast backbone motions, but does increase the average timescale of these motions, most likely due to the increase in viscosity of the cytosol.

Effects of the teach-model-coach-review instructional approach on caregiver use of language support strategies and children's expressive language skills.

PURPOSE: In this study, the authors examined the effects of the Teach-Model-Coach-Review instructional approach on caregivers' use of four enhanced milieu teaching (EMT) language support strategies and on their children's use of expressive language. METHOD: Four caregiver-child dyads participated in a single-subject, multiple-baseline study. Children were between 24 and 42 months of age and had language impairment. Interventionists used the Teach-Model-Coach-Review instructional approach to teach caregivers to use matched turns, expansions, time delays, and milieu teaching prompts during 24 individualized clinic sessions. Caregiver use of each EMT language support strategy and child use of communication targets were the dependent variables. RESULTS: The caregivers demonstrated increases in their use of each EMT language support strategy after instruction. Generalization and maintenance of strategy use to the home was limited, indicating that teaching across routines is necessary to achieve maximal outcomes. All children demonstrated gains in their use of communication targets and in their performance on norm-referenced measures of language. CONCLUSION: The results indicate that the Teach-Model-Coach-Review instructional approach resulted in increased use of EMT language support strategies by caregivers. Caregiver use of these strategies was associated with positive changes in child language skills.

Cytosol has a small effect on protein backbone dynamics.

Cells are crowded with macromolecules, yet most biophysical information about proteins is obtained in dilute solution. To determine the impact of this dichotomy, we used nuclear magnetic resonance spectroscopy to measure the backbone (15)N T(1) and T(2) relaxation times and the {(1)H}-(15)N nuclear Overhauser enhancement (nOe) of uniformly (15)N-enriched apocytochrome b(5) in living Escherichia coli and in dilute solution. These data allowed us to assess the backbone dynamics of this partially folded protein in cells and in dilute solution. The two data sets were analyzed by using the model-free approach. Transfer from dilute solution to the cytosol has a quantitative effect on T(1), T(2), and nOe values. Most of the effects are attributed to an increase in the overall correlation time, caused by the increased viscosity of the cytosol compared to that of the dilute solution. Our main conclusion is that the cytosol does not alter the pattern of backbone dynamics of apocytochrome b(5). Increases in the time scale of both the picosecond and millisecond motions are observed, but the increases are less than approximately 30%.

Protein dynamics in living cells.

A protein's structure is most often used to explain its function, but function also depends on dynamics. To date, protein dynamics have been studied only in vitro under dilute solution conditions where solute concentrations are typically less than 10 g/L, yet proteins function in a crowded environment where the solute concentration can exceed 400 g/L. Does the intracellular environment affect protein dynamics? The answer will help in assessing the biological significance of the NMR-derived dynamics data collected to date. We investigated fast protein dynamics inside living Escherichia coli by using in-cell NMR. The backbone dynamics of apocytochrome b5 were quantified using {1H}-15N nuclear Overhauser effect (nOe) measurements, which characterize motions on the pico- to nanosecond time scale. The overall trend of backbone dynamics remains the same in cells. Some of the nOe values differ, but most of the differences track the increased intracellular viscosity rather than a change in dynamics. Therefore, it appears that dilute solution steady-state {1H}-15N nOe measurements provide biologically relevant information about pico- to nanosecond backbone motion in proteins.

Enzootic transmission of yellow fever virus in Peru.

The prevailing paradigm of yellow fever virus (YFV) ecology in South America is that of wandering epizootics. The virus is believed to move from place to place in epizootic waves involving monkeys and mosquitoes, rather than persistently circulating within particular locales. After a large outbreak of YFV illness in Peru in 1995, we used phylogenetic analyses of virus isolates to reexamine the hypothesis of virus movement. We sequenced a 670-nucleotide fragment of the prM/E gene region from 25 Peruvian YFV samples collected from 1977 to 1999, and delineated six clades representing the states (Departments) of Puno, Pasco, Junin, Ayacucho, San Martin/Huanuco, and Cusco. The concurrent appearance of at least four variants during the 1995 epidemic and the genetic stability of separate virus lineages over time indicate that Peruvian YFV is locally maintained and circulates continuously in discrete foci of enzootic transmission.