An Interdisciplinary Approach to a Dental Information Technology Course

Purpose: To develop an interdisciplinary course to teach dental students about evidence-based dentistry, development of search strategies, critical appraisal of literature, and dental informatics. [See PDF for complete abstract]

A day in the life of PubMed: analysis of a typical day's query log.

OBJECTIVE: To characterize PubMed usage over a typical day and compare it to previous studies of user behavior on Web search engines. DESIGN: We performed a lexical and semantic analysis of 2,689,166 queries issued on PubMed over 24 consecutive hours on a typical day. MEASUREMENTS: We measured the number of queries, number of distinct users, queries per user, terms per query, common terms, Boolean operator use, common phrases, result set size, MeSH categories, used semantic measurements to group queries into sessions, and studied the addition and removal of terms from consecutive queries to gauge search strategies. RESULTS: The size of the result sets from a sample of queries showed a bimodal distribution, with peaks at approximately 3 and 100 results, suggesting that a large group of queries was tightly focused and another was broad. Like Web search engine sessions, most PubMed sessions consisted of a single query. However, PubMed queries contained more terms. CONCLUSION: PubMed's usage profile should be considered when educating users, building user interfaces, and developing future biomedical information retrieval systems.

Occupational therapy articles in serial publications: an analysis of sources.

This study was designed to locate and document serial literature on occupational therapy published since 1900. Emphasis is placed on finding articles on occupational therapy or by occupational therapists from sources other than those normally associated with the professional journals. Multiple sources were used including print indexes, online databases, occupational therapy bibliographies, and tables of contents or yearly indexes. Almost 7,000 articles were identified, not including those published in foreign journals. Occupational therapy publications have increased steadily since 1900, with the most rapid increase during the 1970s and 1980s when five new occupational therapy journals were initiated. Suggestions for formulating search strategies are included.

Modeling Techniques for the High-Resolution Interpretation of Cryo-Electron Microscopy Reconstructions

Essential biological processes are governed by organized, dynamic interactions between multiple biomolecular systems. Complexes are thus formed to enable the biological function and get dissembled as the process is completed. Examples of such processes include the translation of the messenger RNA into protein by the ribosome, the folding of proteins by chaperonins or the entry of viruses in host cells. Understanding these fundamental processes by characterizing the molecular mechanisms that enable then, would allow the (better) design of therapies and drugs. Such molecular mechanisms may be revealed trough the structural elucidation of the biomolecular assemblies at the core of these processes. Various experimental techniques may be applied to investigate the molecular architecture of biomolecular assemblies. High-resolution techniques, such as X-ray crystallography, may solve the atomic structure of the system, but are typically constrained to biomolecules of reduced flexibility and dimensions. In particular, X-ray crystallography requires the sample to form a three dimensional (3D) crystal lattice which is technically di‑cult, if not impossible, to obtain, especially for large, dynamic systems. Often these techniques solve the structure of the different constituent components within the assembly, but encounter difficulties when investigating the entire system. On the other hand, imaging techniques, such as cryo-electron microscopy (cryo-EM), are able to depict large systems in near-native environment, without requiring the formation of crystals. The structures solved by cryo-EM cover a wide range of resolutions, from very low level of detail where only the overall shape of the system is visible, to high-resolution that approach, but not yet reach, atomic level of detail. In this dissertation, several modeling methods are introduced to either integrate cryo-EM datasets with structural data from X-ray crystallography, or to directly interpret the cryo-EM reconstruction. Such computational techniques were developed with the goal of creating an atomic model for the cryo-EM data. The low-resolution reconstructions lack the level of detail to permit a direct atomic interpretation, i.e. one cannot reliably locate the atoms or amino-acid residues within the structure obtained by cryo-EM. Thereby one needs to consider additional information, for example, structural data from other sources such as X-ray crystallography, in order to enable such a high-resolution interpretation. Modeling techniques are thus developed to integrate the structural data from the different biophysical sources, examples including the work described in the manuscript I and II of this dissertation. At intermediate and high-resolution, cryo-EM reconstructions depict consistent 3D folds such as tubular features which in general correspond to alpha-helices. Such features can be annotated and later on used to build the atomic model of the system, see manuscript III as alternative. Three manuscripts are presented as part of the PhD dissertation, each introducing a computational technique that facilitates the interpretation of cryo-EM reconstructions. The first manuscript is an application paper that describes a heuristics to generate the atomic model for the protein envelope of the Rift Valley fever virus. The second manuscript introduces the evolutionary tabu search strategies to enable the integration of multiple component atomic structures with the cryo-EM map of their assembly. Finally, the third manuscript develops further the latter technique and apply it to annotate consistent 3D patterns in intermediate-resolution cryo-EM reconstructions. The first manuscript, titled An assembly model for Rift Valley fever virus, was submitted for publication in the Journal of Molecular Biology. The cryo-EM structure of the Rift Valley fever virus was previously solved at 27Å-resolution by Dr. Freiberg and collaborators. Such reconstruction shows the overall shape of the virus envelope, yet the reduced level of detail prevents the direct atomic interpretation. High-resolution structures are not yet available for the entire virus nor for the two different component glycoproteins that form its envelope. However, homology models may be generated for these glycoproteins based on similar structures that are available at atomic resolutions. The manuscript presents the steps required to identify an atomic model of the entire virus envelope, based on the low-resolution cryo-EM map of the envelope and the homology models of the two glycoproteins. Starting with the results of the exhaustive search to place the two glycoproteins, the model is built iterative by running multiple multi-body refinements to hierarchically generate models for the different regions of the envelope. The generated atomic model is supported by prior knowledge regarding virus biology and contains valuable information about the molecular architecture of the system. It provides the basis for further investigations seeking to reveal different processes in which the virus is involved such as assembly or fusion. The second manuscript was recently published in the of Journal of Structural Biology (doi:10.1016/j.jsb.2009.12.028) under the title Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions. This manuscript introduces the evolutionary tabu search strategies applied to enable a multi-body registration. This technique is a hybrid approach that combines a genetic algorithm with a tabu search strategy to promote the proper exploration of the high-dimensional search space. Similar to the Rift Valley fever virus, it is common that the structure of a large multi-component assembly is available at low-resolution from cryo-EM, while high-resolution structures are solved for the different components but lack for the entire system. Evolutionary tabu search strategies enable the building of an atomic model for the entire system by considering simultaneously the different components. Such registration indirectly introduces spatial constrains as all components need to be placed within the assembly, enabling the proper docked in the low-resolution map of the entire assembly. Along with the method description, the manuscript covers the validation, presenting the benefit of the technique in both synthetic and experimental test cases. Such approach successfully docked multiple components up to resolutions of 40Å. The third manuscript is entitled Evolutionary Bidirectional Expansion for the Annotation of Alpha Helices in Electron Cryo-Microscopy Reconstructions and was submitted for publication in the Journal of Structural Biology. The modeling approach described in this manuscript applies the evolutionary tabu search strategies in combination with the bidirectional expansion to annotate secondary structure elements in intermediate resolution cryo-EM reconstructions. In particular, secondary structure elements such as alpha helices show consistent patterns in cryo-EM data, and are visible as rod-like patterns of high density. The evolutionary tabu search strategy is applied to identify the placement of the different alpha helices, while the bidirectional expansion characterizes their length and curvature. The manuscript presents the validation of the approach at resolutions ranging between 6 and 14Å, a level of detail where alpha helices are visible. Up to resolution of 12 Å, the method measures sensitivities between 70-100% as estimated in experimental test cases, i.e. 70-100% of the alpha-helices were correctly predicted in an automatic manner in the experimental data. The three manuscripts presented in this PhD dissertation cover different computation methods for the integration and interpretation of cryo-EM reconstructions. The methods were developed in the molecular modeling software Sculptor (http://sculptor.biomachina.org) and are available for the scientific community interested in the multi-resolution modeling of cryo-EM data. The work spans a wide range of resolution covering multi-body refinement and registration at low-resolution along with annotation of consistent patterns at high-resolution. Such methods are essential for the modeling of cryo-EM data, and may be applied in other fields where similar spatial problems are encountered, such as medical imaging.

Strategies for obesity prevention in child care settings: A literature review

Background. Children in the age group of 2-5 years spend substantial amount of time during the day in some kind of childcare setting. These settings are an excellent environmental infrastructure to enhance their nutrition and physical activity behavior and to promote healthy eating and physical activity habits. Due to the steep rise in overweight and obesity among children in the past three decades, it becomes essential to intervene early. There exists a need for literature on a comprehensive and sustainable approach to obesity prevention for younger children in these settings. ^ Methods. Systematic literature search was undertaken using databases like Medline Ovid, Pubmed, Medline Ebsco, and Cochrane Library. Articles published in English as well as English language abstracts of foreign articles were included. The inclusion criteria were as follows: (1) Studies conducted in any part of the world exploring relevant themes and a child care or preschool setting would be included. (2) The interventions promoted physical activity, nutrition/healthy eating/improved diet, reduced television viewing, reduced BMI, changed knowledge and behavior of children and or staff or affected policy/standards/regulations. (3) The population was children in the age group of at least 2 years to 5 years. (4) Articles published in English and English language abstracts for foreign articles would be included. ^ Results. 16 articles were included in the review that consisted of primary interventions in the form of randomized control trials or pre-post interventions were conducted in a preschool or child care or day care setting only. The outcomes pertaining to healthy weight in children were increased vegetable intake, reduced BMI and increased knowledge among others. ^ Conclusion. There is a dearth of data on strong intervention trials in the child care setting. Preschool research studies in the young children that have been conducted are not strong enough. There is a need for more randomized control trials and a well planned evaluation in the preschool age children. There is a need to develop outcome measures that can accurately assess the changes in diet and physical activity in this age group. Child care nutrition and physical activity standards need to be made stringent. ^