Identifying the semantics of eligibility criteria of clinical trials based on relevant medical ontologies

An important objective of the INTEGRATE project1 is to build tools that support the efficient execution of post-genomic multi-centric clinical trials in breast cancer, which includes the automatic assessment of the eligibility of patients for available trials. The population suited to be enrolled in a trial is described by a set of free-text eligibility criteria that are both syntactically and semantically complex. At the same time, the assessment of the eligibility of a patient for a trial requires the (machineprocessable) understanding of the semantics of the eligibility criteria in order to further evaluate if the patient data available for example in the hospital EHR satisfies these criteria. This paper presents an analysis of the semantics of the clinical trial eligibility criteria based on relevant medical ontologies in the clinical research domain: SNOMED-CT, LOINC, MedDRA. We detect subsets of these widely-adopted ontologies that characterize the semantics of the eligibility criteria of trials in various clinical domains and compare these sets. Next, we evaluate the occurrence frequency of the concepts in the concrete case of breast cancer (which is our first application domain) in order to provide meaningful priorities for the task of binding/mapping these ontology concepts to the actual patient data. We further assess the effort required to extend our approach to new domains in terms of additional semantic mappings that need to be developed.

Supporting patient screening to identify suitable clinical trials.

To support the efficient execution of post-genomic multi-centric clinical trials in breast cancer we propose a solution that streamlines the assessment of the eligibility of patients for available trials. The assessment of the eligibility of a patient for a trial requires evaluating whether each eligibility criterion is satisfied and is often a time consuming and manual task. The main focus in the literature has been on proposing different methods for modelling and formalizing the eligibility criteria. However the current adoption of these approaches in clinical care is limited. Less effort has been dedicated to the automatic matching of criteria to the patient data managed in clinical care. We address both aspects and propose a scalable, efficient and pragmatic patient screening solution enabling automatic evaluation of eligibility of patients for a relevant set of trials. This covers the flexible formalization of criteria and of other relevant trial metadata and the efficient management of these representations.

A SENSIBILIDADE CULTURAL DO ADVENTISMO COMO MODELO MISSIOLÓGICO EM GRANDES CENTROS URBANOS: UMA ANÁLISE DE IGREJAS ADVENTISTAS ÉTNICAS NA CIDADE DE SÃO PAULO

Esta pesquisa objetiva analisar o desenvolvimento da missão adventista na cidade de São Paulo em busca de um modelo missiológico para centros urbanos. São Paulo, uma das maiores metrópoles do mundo tem uma formação cultural plural, não apenas pelas forças atuantes da modernização, secularização, globalização e pós-modernidade. A composição da população da cidade possui uma gênese étnica plural. Além da matriz autóctone indígena, do colonizador branco europeu e dos escravos africanos, desde o início do século XIX chegaram outros imigrantes, europeus e asiáticos. Nas primeiras décadas do século XX, o Brasil foi o país que mais recebeu imigrantes em todo o mundo. Estima-se que nos anos de 1920, apenas um terço da população na cidade de São Paulo fosse de brasileiros, o restante era composto por imigrantes. A inserção do adventismo em São Paulo se deu por missionários imigrantes que trabalharam primeiro com outros imigrantes antes de evangelizar e desenvolver a missão adventista com os brasileiros nacionais. De alguma forma, esse início deixou marcas na missão adventista paulistana. São Paulo é hoje a cidade com o maior número total de adventistas no mundo e a única com Igrejas Adventistas étnicas que atendem cinco grupos étnicos distintos: japoneses, coreanos, judeus, árabes e bolivianos/peruanos. Esta pesquisa busca investigar a formação de uma sensibilidade cultural no adventismo paulistano que lhe permitiu dialogar com a pluralidade cultural da metrópole paulistana.

Substrate specificity determinants in the farnesyltransferase β-subunit

Protein prenyltransferases catalyze the covalent attachment of isoprenoid lipids (farnesyl or geranylgeranyl) to a cysteine near the C terminus of their substrates. This study explored the specificity determinants for interactions between the farnesyltransferase of Saccharomyces cerevisiae and its protein substrates. A series of substitutions at amino acid 149 of the farnesyltransferase β-subunit were tested in combination with a series of substitutions at the C-terminal amino acid of CaaX protein substrates Ras2p and a-factor. Efficient prenylation was observed when oppositely charged amino acids were present at amino acid 149 of the yeast farnesyltransferase β-subunit and the C-terminal amino acid of the CaaX protein substrate, but not when like charges were present at these positions. This evidence for electrostatic interaction between amino acid 149 and the C-terminal amino acid of CaaX protein substrates leads to the prediction that the C-terminal amino acid of the protein substrate binds near amino acid 149 of the yeast farnesyltransferase β-subunit.

Sequence Determinants for Regulated Degradation of Yeast 3-Hydroxy-3-Methylglutaryl-CoA Reductase, an Integral Endoplasmic Reticulum Membrane Protein

The degradation rate of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-R), a key enzyme of the mevalonate pathway, is regulated through a feedback mechanism by the mevalonate pathway. To discover the intrinsic determinants involved in the regulated degradation of the yeast HMG-R isozyme Hmg2p, we replaced small regions of the Hmg2p transmembrane domain with the corresponding regions from the other, stable yeast HMG-R isozyme Hmg1p. When the first 26 amino acids of Hmg2p were replaced with the same region from Hmg1p, Hmg2p was stabilized. The stability of this mutant was not due to mislocalization, but rather to an inability to be recognized for degradation. When amino acid residues 27–54 of Hmg2p were replaced with those from Hmg1p, the mutant was still degraded, but its degradation rate was poorly regulated. The degradation of this mutant was still dependent on the first 26 amino acid residues and on the function of the HRD genes. These mutants showed altered ubiquitination levels that were well correlated with their degradative phenotypes. Neither determinant was sufficient to impart regulated degradation to Hmg1p. These studies provide evidence that there are sequence determinants in Hmg2p necessary for degradation and optimal regulation, and that independent processes may be involved in Hmg2p degradation and its regulation.

Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects.

At least three distinct beta-adrenergic receptor (beta-AR) subtypes exist in mammals. These receptors modulate a wide variety of processes, from development and behavior, to cardiac function, metabolism, and smooth muscle tone. To understand the roles that individual beta-AR subtypes play in these processes, we have used the technique of gene targeting to create homozygous beta 1-AR null mutants (beta 1-AR -/-) in mice. The majority of beta 1-AR -/- mice die prenatally, and the penetrance of lethality shows strain dependence. Beta l-AR -/- mice that do survive to adulthood appear normal, but lack the chronotropic and inotropic responses seen in wild-type mice when beta-AR agonists such as isoproterenol are administered. Moreover, this lack of responsiveness is accompanied by markedly reduced stimulation of adenylate cyclase in cardiac membranes from beta 1-AR -/- mice. These findings occur despite persistent cardiac beta 2-AR expression, demonstrating the importance of beta 1-ARs for proper mouse development and cardiac function, while highlighting functional differences between beta-AR subtypes.

Closer to life : the work of sari dienes

Like many of her female contemporaries, artist Sari Dienes’s contributions to the art historical dialogue have been largely overlooked in favor of her male counterparts. Often seen as a mentor and mother figure to neo-Dada artists Jasper Johns and Robert Rauschenberg, Dienes was an active member of the New York avant-garde circle surrounding composer/choreographer duo John Cage and Merce Cunningham in the 1950s and 1960s. These social relationships are central to the existing discourse on Sari Dienes, while her work remains little discussed. The fact that her dynamic, ever-changing style lacked aesthetic consistency was commonly lamented by notable figures such as Betty Parsons, however, I argue that Dienes’s diverse oeuvre is unified by her philosophies on art and life. The unification of art and life, denoted clearly by Dienes’s use of the found object, experimentation and chance happenings, and sensory experience, marks her as an innovator and catalyst in the neo-Dada movement as well as in other experimental art endeavors that took place in the aftermath of Abstract Expressionism.

Bill of lading for shipment of four boxes of books, Oct. 20, 1764

This bill of lading is from Jasper Mauduit's shipment of books (his own gift and those bequeathed by Dr. Avery) to Andrew Oliver. The books were shipped from London to Boston via a ship called Hale Galley, under the direction of Captain Harris Hatch.

Proceedings in Tanner vs. Hall, 1758, June

Copy of the proceedings in the case of Benjamin Tanner vs. Jasper Hall of Kingston (Jamaica), relating to various lands, etc. With the autographs of Henry Moore, governor, and John Arnold, registrar of the high court.

Physical properties and bulk organic geochemical results for sediments from DSDP Hole 96-619

The concentration and carbon isotopic composition (d13C) of sedimentary organic carbon (C_org), N/C ratios, and terrigenous and marine d13C_org endmembers form a basis from which to address problems of Late Quaternary glacial-interglacial climatic variability in a 208.7 m hydraulic piston core (DSDP 619) from the Pigmy Basin in the northern Gulf of Mexico. While interpretations of sedimentary d13C_org time series records are often not unique, paired analyses of d13C_org and N/C are consistent with the hypothesis that the C_org in the Pigmy Basin is a climatically determined mixture of C3-photosynthetic terrigenous and marine organic matter, confirming the earlier d13C_org model of Sackett (1964). A high resolution (~1.4-2.9 Ka/sample) d13C_org record shows that sedimentary organic carbon in interglacial oxygen isotope (sub)stages 1 and 5a-b are enriched in 13C (average +/-1 sigma values are -24.2+/-1.2? and -22.9+/-0.7? relative to PDB, respectively) while glacial isotope stage values 2 are relatively depleted (-25.6+/-0.5?). Concentrations of terrigenous and marine sedimentary organic carbon are calculated for the first time using d13C_org and C_org measurements, and empirically determined terrigenous and marine d13C_org endmembers. The net accumulation rate of terrigenous organic carbon is 4.3+/-2.6 times higher in isotope stages 2-4 than in (sub)stages 1 and 5a-b, recording higher erosion rates of terrigenous organic material in glacial times. The concentration and net accumulation rates of marine and terrigenous C_org suggest that the nutrient-bearing plume of the Mississippi River may have advanced and retreated across the Pigmy Basin as sea level fell and rose in response to glacial-interglacial sea level change.

The Detroit Observatory of the University of Michigan

Richard Bull, architect. Known at various times as Detroit Observatory, Campus Observatory, Old Observatory. Original image in color