Negative findings in electronic health records and biomedical ontologies: a realist approach

PURPOSE—A substantial fraction of the observations made by clinicians and entered into patient records are expressed by means of negation or by using terms which contain negative qualifiers (as in “absence of pulse” or “surgical procedure not performed”). This seems at first sight to present problems for ontologies, terminologies and data repositories that adhere to a realist view and thus reject any reference to putative non-existing entities. Basic Formal Ontology (BFO) and Referent Tracking (RT) are examples of such paradigms. The purpose of the research here described was to test a proposal to capture negative findings in electronic health record systems based on BFO and RT. METHODS—We analysed a series of negative findings encountered in 748 sentences taken from 41 patient charts. We classified the phenomena described in terms of the various top-level categories and relations defined in BFO, taking into account the role of negation in the corresponding descriptions. We also studied terms from SNOMED-CT containing one or other form of negation. We then explored ways to represent the described phenomena by means of the types of representational units available to realist ontologies such as BFO. RESULTS—We introduced a new family of ‘lacks’ relations into the OBO Relation Ontology. The relation lacks_part, for example, defined in terms of the positive relation part_of, holds between a particular p and a universal U when p has no instance of U as part. Since p and U both exist, assertions involving ‘lacks_part’ and its cognates meet the requirements of positivity. CONCLUSION—By expanding the OBO Relation Ontology, we were able to accommodate nearly all occurrences of negative findings in the sample studied

OntONeo: The Obstetric and Neonatal Ontology

This paper presents the Obstetric and Neonatal Ontology (OntONeo). This ontology has been created to provide a consensus representation of salient electronic health record (EHR) data and to serve interoperability of the associated data and information systems. More generally, it will serve interoperability of clinical and translational data, for example deriving from genomics disciplines and from clinical trials. Interoperability of EHR data is important to ensuring continuity of care during the prenatal and postnatal periods for both mother and child. As a strategy to advance such interoperability we use an approach based on ontological realism and on the ontology development principles of the Open Biomedical Ontologies Foundry, including reuse of reference ontologies wherever possible. We describe the structure and coverage domain of OntONeo and the process of creating and maintaining the ontology

Dealing with elements of medical encounters: An approach based on ontological realism

Electronic health records (EHRs) serve as repositories of documented data collected in a health care encounter. An EHR records information about who receives, who provides the health care and about the place where the encounter happens. We also observe additional elements relating to social relations in which the healthcare consumer is involved. To provide a consensus representation of common data and to enhance interoperability between different EHR repositories we have created a solution grounded in formal ontology. Here, we present how an ontology for the obstetric and neonatal domain deals with these general elements documented in health care encounters. Our goal is to promote the interoperability of information among EHRs created in different specialties. To develop our ontology, we used two main approaches: one based on ontological realism, the other based on the principles of the OBO Foundry, including reuse of reference ontologies

Referent Tracking: The Problem of Negative Findings

The paradigm of referent tracking is based on a realist presupposition which rejects so-called negative entities (congenital absent nipple, and the like) as spurious. How, then, can a referent tracking-based Electronic Health Record deal with what are standardly called ‘negative findings’? To answer this question we carried out an analysis of some 748 sentences drawn from patient charts and containing some form of negation. Our analysis shows that to deal with these sentences we need to introduce a new ontological relationship between a particular and a universal, which holds when no instance of the universal has a specific qualified ontological relation with the particular. This relation is found to be able to accommodate nearly all occurrences of negative findings in the examined sample, in ways which involve no reference to negative entities

Combating Ebola with Repurposed Therapeutics Using the CANDO Platform

Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to have caused more than 11,000 fatalities. The countries worst affected are also among the poorest in the world. Given the complexities, time, and resources required for a novel drug development, finding efficient drug discovery pathways is going to be crucial in the fight against future outbreaks. We have developed a Computational Analysis of Novel Drug Opportunities (CANDO) platform based on the hypothesis that drugs function by interacting with multiple protein targets to create a molecular interaction signature that can be exploited for rapid therapeutic repurposing and discovery. We used the CANDO platform to identify and rank FDA-approved drug candidates that bind and inhibit all proteins encoded by the genomes of five different Ebola virus strains. Top ranking drug candidates for EVD treatment generated by CANDO were compared to in vitro screening studies against Ebola virus-like particles (VLPs) by Kouznetsova et al. and genetically engineered Ebola virus and cell viability studies by Johansen et al. to identify drug overlaps between the in virtuale and in vitro studies as putative treatments for future EVD outbreaks. Our results indicate that integrating computational docking predictions on a proteomic scale with results from in vitro screening studies may be used to select and prioritize compounds for further in vivo and clinical testing. This approach will significantly reduce the lead time, risk, cost, and resources required to determine efficacious therapies against future EVD outbreaks

Construção de ontologia na prática: um estudo de caso aplicado ao domínio obstétrico

O volume de informação e a variedade de fontes de informação gera desafios para a integração informacional. A necessidade de integração de informação entre sistemas de informação distintos alavancou pesquisas para identificar alternativas capazes de proporcionar interoperabilidade semântica entre sistemas, ou seja, a especificação da informação sem gerar ambiguidades. Como contribuição da Ciência da Informação, as ontologias servem como alternativa de padronização semântica das informações. Entretanto, o processo de construção de ontologias ainda gera muita dúvida entre pesquisadores. Muitos autores descrevem metodologias para a construção de ontologias, mas observa-se uma lacuna entre os métodos descritos e a sua aplicação na prática. Busca-se demonstrar na prática a construção de uma ontologia que adotou duas consolidadas metodologias: o realismo ontológico e a metodologia NeOn. Em relação aos métodos e procedimentos técnicos realizados, esta pesquisa é um estudo de caso que investiga a prática da construção de uma ontologia biomédica no domínio obstétrico, com o objetivo de descrever e explicar o processo de construção da ontologia praticado. Espera-se contribuir com o avanço da pesquisa em construção de ontologias no campo da Ciência da Informação, dada sua aplicação na solução problemas de organização e recuperação de informações em ambientes informacionais de diversos campos científicos

Transverse Optical Mode Patterns for an RF Excited Ar-He-Xe Laser

Transverse optical modes for an RF excited Ar-He-Xe laser are studied both experimentally and theoretically. A diffraction model for a waveguide with a nonsaturable gain and refractive index gradients placed between two plane mirrors is formulated. The effects of gain and diffraction index gradients and of diffraction in free space are evaluated for typical experimental conditions. A direct comparison between theoretical mode patterns and experimentally measured ones at distances of 17 and 114 cm from the output mirror demonstrated a satisfactory agreement for various laser wavelengths and gas mixture composition

Managing Surface Water Inputs to Reduce Phosphorus Losses from Cranberry Farms

Abstract: In Massachusetts, cranberry (Vaccinium macrocarpon Ait.) production accounts for one-fourth of US cranberry supply, but water quality concerns, water use, and wetland protection laws threaten the sustainability and future viability of the state’s cranberry industry. Pond water used for harvest and winter flooding accounts for up to two-thirds of phosphorus (P) losses in drainage waters. Consequently, use of P sorbing salts to treat pond water holds promise in the mitigation of P losses from cranberry farms. Laboratory evaluation of aluminum (Al)-, iron (Fe)-, and calcium (Ca)-based salts was conducted to determine the application rate required for reducing P in shallow (0.4 m) and deep (3.2 m) water ponds used for cranberry production. Limited P removal (\u3c22%) with calcium carbonate and calcium sulfate was consistent with their relatively low solubility in water. Calcium hydroxide reduced total P up to 66%, but increases in pond water pH (\u3e8) could be detrimental to cranberry production. Ferric sulfate and aluminum sulfate applications of 15 mg L−1 (ppm) resulted in near-complete removal of total P, which decreased from 49 ± 3 to \u3c10 mg P L−1 (ppb). However, ferric sulfate application lowered pH below the recommend range for cranberry soils. Field testing of aluminum sulfate demonstrated that at a dose of 15 mg L−1 (~1.4 Al mg L−1), total P in pond water was reduced by 78 to 93%. Laboratory and field experiments support the recommendation of aluminum sulfate as a cost-effective remedial strategy for reducing elevated P in surface water used for cranberry production

Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits

The cyclic AMP (cAMP)-response element binding protein (CREB) is an activity-dependent transcription factor playing a role in synaptic plasticity, learning and memory, and emotional behavior. However, the impact of Creb ablation on rodent behavior is vague as e.g. memory performance of different Creb mutant mice depends on the specific type of mutation per se but additionally on the background and learning protocol differences. Here we present the first targeted ablation of CREB induced during adulthood selectively in principal forebrain neurons in a pure background strain of C57BL/6 mice. All hippocampal principal neurons exhibited lack of CREB expression. Mutant mice showed a severe anxiety phenotype in the openfield and novel object exploration test as well as in the Dark-Light Box Test, but unaltered hippocampus-dependent long-term memory in the Morris water maze and in context dependent fear conditioning. On the molecular level, CREB ablation led to CREM up regulation in the hippocampus and frontal cortex which may at least in part compensate for the loss of CREB. BDNF, a postulated CREB target gene, was down regulated in the frontal lobe but not in the hippocampus; neurogenesis remained unaltered. Our data indicate that in the adult mouse forebrain the late onset of CREB ablation can, in case of memory functionality, be compensated for and is not essential for memory consolidation and retrieval during adulthood. In contrast, the presence of CREB protein during adulthood seems to be pivotal for the regulation of emotional behavior