The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

Background: Although convolutional neural networks (CNNs) achieve high diagnostic accuracy for detecting Alzheimer’s disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap as they allow the visualization of key input image features that drive the decision of the model. We investigated whether models with higher accuracy (...) also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N = 663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including in total N = 1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps, thereby allowing intuitive model inspection. Results: Across the three independent datasets, group separation showed high accuracy for AD dementia versus controls (AUC ≥ 0.91) and moderate accuracy for amnestic MCI versus controls (AUC ≈ 0.74). Relevance maps indicated that hippocampal atrophy was considered the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson’s r ≈ −0.86, p < 0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels. The high hippocampus relevance scores as well as the high performance achieved in independent samples support the validity of the CNN models in the detection of AD-related MRI abnormalities. The presented data-driven and hypothesis-free CNN modeling approach might provide a useful tool to automatically derive discriminative features for complex diagnostic tasks where clear clinical criteria are still missing, for instance for the differential diagnosis between various types of dementia. (shrink)

Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced vaccine (...) data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented. (shrink)

Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the (...) variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of addiction memory. (shrink)

Originally published in 1936, this book presents the ancient Greek text of the paraphrases and quotations of Zeno's philosophical arguments, together with a facing-page English translation and editorial commentary. Detailed notes are incorporated throughout and a bibliography is also included. This book will be of value to anyone with an interest in Zeno and ancient philosophy.

This paper focuses on abduction as explicit or readily formulatable inference to possible explanatory hypotheses--as contrasted with inference to conceptual innovations or abductive logic as a cycle of hypotheses, deduction of consequences and inductive testing. Inference to an explanation is often a matter of projection or extrapolation of elements of accepted theory for the solution of outstanding problems in particular domains of inquiry. I say "projections or extrapolation" of accepted theory, but I mean to point to something broader and suggest (...) how elements of accepted theory constrain emergent models and plausible inferences to explanations--in a quasi-rationalist fashion. I draw on illustrations from quantum gravity below just because there is so little direct evidence available in the field. It is in such cases that Peirce's discussions of abductive inference provide the most plausible support for the idea of a logic of abduction--as inference to readily formulatable explanatory hypotheses. The possible need for conceptual innovation points to the limits on the possibility of a logic of abduction of a more rationalistic character--selecting uniquely superior explanations. Abduction conceived as a repeated cycle of inquiry also points to limits on our expectations for an abductive logic. My chief point is that the character of inference to an explanation, viewed below as embedded within arguments from analogy, is so little compelling, as a matter of logical form alone, that there will always be a pluralism of plausible alternatives among untested hypotheses and inferences to them--calling for some comparative evaluation. This point leads on to some consideration of the virtues of hypotheses--as a description of the range of this pluralism. (shrink)

The development of transplantation technology increasingly places before society a multitude of diverse, complex ethical and legal problems. The subject is the more complex because of the various divergent interests involved. There are the interests of the donor of organs, who has a right to protection of his legal position, and those of the patient in need of an often lifesaving organ. There are also the interests of the donor’s relatives, after his death, and those of the transplantation surgeons. The (...) international dimension of transplantation technology makes the picture even more complicated. Though this article is devoted to the European situation, the problems are similar all over the world. (shrink)

Background The consistency of codes governing disclosure of terminal illness to patients and families in Islamic countries has not been studied until now. Objectives To review available codes on disclosure of terminal illness in Islamic countries. Data source and extraction Data were extracted through searches on Google and PubMed. Codes related to disclosure of terminal illness to patients or families were abstracted, and then classified independently by the three authors. Data synthesis Codes for 14 Islamic countries were located. Five codes (...) were silent regarding informing the patient, seven allowed concealment, one mandated disclosure and one prohibited disclosure. Five codes were silent regarding informing the family, four allowed disclosure and five mandated/recommended disclosure. The Islamic Organization for Medical Sciences code was silent on both issues. Conclusion Codes regarding disclosure of terminal illness to patients and families differed markedly among Islamic countries. They were silent in one-third of the codes, and tended to favour a paternalistic/utilitarian, family-centred approach over an autonomous, patient-centred approach. (shrink)

This book covers the author's conception of God aside from any religion. He does not come from a religious view in order to transmit the truest conception of God that he is capable of because any religion, whatever it might be, always claims God for itself in an exclusionary fashion. In other words, you must be a follower of the chosen faith before God will accept you into his kingdom. Wells rejects this view. Any man or woman who accepts God's (...) love as one person connecting to their own creator, is fine. An intermediary, despite what they might crow from whatever pulpits they use, is not necessary. We are all God's children. We are all seeking the same God, so to be dogmatic within a certain exclusionary faith is small-minded and petty. If you want to grow up, spiritually, then this book is for you. (shrink)

Open peer commentary on the article “Religion: A Radical-Constructivist Perspective” by Andreas Quale. Upshot: Quale offers a way of categorizing religious discourse based on radical constructivism. This commentary raises questions about the inter-relation of cognitive and non-cognitive knowledge, the role of testimony in learning about religion, and whether knowledge and belief have different roles in cognitive and non-cognitive knowledge, and suggests that Quale’s analysis opens a tolerant perspective on religious discourse.