Ontologies for Neuroscience: What are they and What are they Good for?

Current information technology practices in neuroscience make it difficult to understand the organization of the brain across spatial scales. Subcellular junctional connectivity, cytoarchitectural local connectivity, and long-range topographical connectivity are just a few of the relevant data domains that must be synthesized in order to make sense of the brain. However, due to the heterogeneity of the data produced within these domains, the landscape of multiscale neuroscience data is fragmented. A standard framework for neuroscience data is needed to bridge existing digital data resources and to help in the conceptual unification of the multiple disciplines of neuroscience. Using our efforts in building ontologies for neuroscience as an example, we examine the benefits and limits of ontologies as a solution for this data integration problem. We provide several examples of their application to problems of image annotation, content-based retrieval of structural data, and integration of data across scales and researchers

Norton Healthcare: A Strong Payer-Provider Partnership for the Journey to Accountable Care

Examines the progress of an integrated healthcare delivery system in forming an accountable care organization with payer partners as part of the Brookings-Dartmouth ACO Pilot Program, including a focus on performance measurement and reporting

HealthCare Partners: Building on a Foundation of Global Risk Management to Achieve Accountable Care

Describes the progress of a medical group and independent practice association in forming an accountable care organization by working with insurers as part of the Brookings-Dartmouth ACO Pilot Program. Lists lessons learned and elements of success

Four Health Care Organizations' Efforts to Improve Patient Care and Reduce Costs

Synthesizes findings from four case studies in the Brookings-Dartmouth ACO Pilot Program about forming integrated systems that can deliver accountable care under shared-savings agreements with private payers

A Formal Ontology of Subcellular Neuroanatomy

The complexity of the nervous system requires high-resolution microscopy to resolve the detailed 3D structure of nerve cells and supracellular domains. The analysis of such imaging data to extract cellular surfaces and cell components often requires the combination of expert human knowledge with carefully engineered software tools. In an effort to make better tools to assist humans in this endeavor, create a more accessible and permanent record of their data, and to aid the process of constructing complex and detailed computational models, we have created a core of formalized knowledge about the structure of the nervous system and have integrated that core into several software applications. In this paper, we describe the structure and content of a formal ontology whose scope is the subcellular anatomy of the nervous system (SAO), covering nerve cells, their parts, and interactions between these parts. Many applications of this ontology to image annotation, content-based retrieval of structural data, and integration of shared data across scales and researchers are also described

Development and use of Ontologies Inside the Neuroscience Information Framework: A Practical Approach

An initiative of the NIH Blueprint for neuroscience research, the Neuroscience Information Framework (NIF) project advances neuroscience by enabling discovery and access to public research data and tools worldwide through an open source, semantically enhanced search portal. One of the critical components for the overall NIF system, the NIF Standardized Ontologies (NIFSTD), provides an extensive collection of standard neuroscience concepts along with their synonyms and relationships. The knowledge models defined in the NIFSTD ontologies enable an effective concept-based search over heterogeneous types of web-accessible information entities in NIF’s production system. NIFSTD covers major domains in neuroscience, including diseases, brain anatomy, cell types, sub-cellular anatomy, small molecules, techniques, and resource descriptors. Since the first production release in 2008, NIF has grown significantly in content and functionality, particularly with respect to the ontologies and ontology-based services that drive the NIF system. We present here on the structure, design principles, community engagement, and the current state of NIFSTD ontologies

The potential impact of vaccine passports on inclination to accept COVID-19 vaccinations in the United Kingdom: Evidence from a large cross-sectional survey and modeling study.

BACKGROUND: The UK Government is considering the introduction of vaccine passports for domestic use and to facilitate international travel for UK residents. Although vaccine incentivisation has been cited as a motivating factor for vaccine passports, it is unclear whether vaccine passports are likely to increase inclination to accept a COVID-19 vaccine. METHODS: We conducted a large-scale national survey in the UK of 17,611 adults between 9 and 27 April 2021. Bayesian multilevel regression and poststratification is used to provide unbiased national-level estimates of the impact of the introduction of vaccine passports on inclination to accept COVID-19 vaccines and identify the differential impact of passports on uptake inclination across socio-demographic groups. FINDINGS: We find that a large minority of respondents report that vaccination passports for domestic use (46·5%) or international travel (42·0%) would make them no more or less inclined to accept a COVID-19 vaccine and a sizeable minority of respondents also state that they would 'definitely' accept a COVID-19 vaccine and that vaccine passports would make them more inclined to vaccinate (48·8% for domestic use and 42·9% for international travel). However, we find that the introduction of vaccine passports will likely lower inclination to accept a COVID-19 vaccine once baseline vaccination intent has been adjusted for. This decrease is larger if passports were required for domestic use rather than for facilitating international travel. Being male (OR 0·87, 0·76 to 0·99) and having degree qualifications (OR 0·84, 0·72 to 0·94) is associated with a decreased inclination to vaccinate if passports were required for domestic use (while accounting for baseline vaccination intent), while Christians (OR 1·23, 1·08 to 1·41) have an increased inclination over atheists or agnostics. Change in inclination is strongly connected to stated vaccination intent and will therefore unlikely shift attitudes among Black or Black British respondents, younger age groups, and non-English speakers. INTERPRETATION: Our findings should be interpreted in light of sub-national trends in uptake rates across the UK, as our results suggest that passports may be viewed less positively among socio-demographic groups that cluster in large urban areas. We call for further evidence on the impact of vaccine certification and the potential fallout for routine immunization programmes in both the UK and in wider global settings, especially those with low overall trust in vaccinations. FUNDING: This survey was funded by the Merck Investigator Studies Program (MISP)

Supernova Enrichment of Dwarf Spheroidal Galaxies

(Abridged) Many dwarf galaxies exhibit sub-Solar metallicities, with some star-to-star variation, despite often containing multiple generations of stars. The total metal content in these systems is much less than expected from the heavy element production of massive stars in each episode of star formation. Such a deficiency implies that a substantial fraction of the enriched material has been lost from these small galaxies. Mass ejection from dwarf galaxies may have important consequences for the evolution of the intergalactic medium and for the evolution of massive galaxies, which themselves may have formed via the merger of smaller systems. We report here the results of three-dimensional simulations of the evolution of supernova-enriched gas within dwarf spheroidal galaxies (dSph's), with the aim of determining the retention efficiency of supernova ejecta. We consider two galaxy models, selected to represent opposite ends of the dSph sequence. For each model galaxy we investigate a number of scenarios, ranging from a single supernova in smooth gas distributions to more complex multiple supernovae in highly disturbed gas distributions. The results of these investigations suggest that, for low star-formation efficiencies, it is difficult to completely expel the enriched material from the galaxy. Most of the enriched gas is, however, lost from the core of the galaxy following multiple supernovae, especially if the interstellar medium is already highly disturbed by processes such as photo-ionization and stellar winds. If subsequent star formation occurs predominantly within the core where most of the residual gas is concentrated, then these results could explain the poor self-enrichment efficiency observed in dwarf galaxies.Comment: 29 pages, 10 figures, to appear in Astrophysical Journa

p53 Activation by Knockdown Technologies

Morpholino phosphorodiamidate antisense oligonucleotides (MOs) and short interfering RNAs (siRNAs) are commonly used platforms to study gene function by sequence-specific knockdown. Both technologies, however, can elicit undesirable off-target effects. We have used several model genes to study these effects in detail in the zebrafish, Danio rerio. Using the zebrafish embryo as a template, correct and mistargeting effects are readily discernible through direct comparison of MO-injected animals with well-studied mutants. We show here indistinguishable off-targeting effects for both maternal and zygotic mRNAs and for both translational and splice-site targeting MOs. The major off-targeting effect is mediated through p53 activation, as detected through the transferase-mediated dUTP nick end labeling assay, acridine orange, and p21 transcriptional activation assays. Concurrent knockdown of p53 specifically ameliorates the cell death induced by MO off-targeting. Importantly, reversal of p53-dependent cell death by p53 knockdown does not affect specific loss of gene function, such as the cell death caused by loss of function of chordin. Interestingly, quantitative reverse-transcriptase PCR, microarrays and whole-mount in situ hybridization assays show that MO off-targeting effects are accompanied by diagnostic transcription of an N-terminal truncated p53 isoform that uses a recently recognized internal p53 promoter. We show here that MO off-targeting results in induction of a p53-dependent cell death pathway. p53 activation has also recently been shown to be an unspecified off-target effect of siRNAs. Both commonly used knockdown technologies can thus induce secondary but sequence-specific p53 activation. p53 inhibition could potentially be applicable to other systems to suppress off-target effects caused by other knockdown technologies