Implications of observation-fact modifiers to i2b2 ontologies

Biomedical translational research can be facilitated by integrating clinical and research data. In particular, study cohort identification and hypothesis generation is enabled by the mining of integrated clinical observations and research resources. The informatics for integrating biology and the bedside, or i2b2, framework is widely used for this biomedical data mining. The i2b2 star schema data model using entity-attribute-value (EA V) formatted concepts is a very efficient strategy for querying large amounts of data. However, until the most recent i2b2 release, the utility of the platform was somewhat constrained by the limitations on being able to express facts about facts - i.e., modify the observations about the patients. We have found that exploiting the new modifier functionality has significantly and favorably impacted the design of i2b2 ontologies, leading to easier and more meaningful query results. Copyright © 2011 IEEE

Use Case and Application Requirements for a Protocol Lifecycle Tracking Tool, with a Focus on the Trial Initiation Phase

The time required to initiate clinical trials, from declaration of the investigator’s intent to opening of the study for participant accrual, is cited as often being so long that clinical research is seriously impeded. Efforts to improve operational efficiency of trial initiation are confounded by the work flow complexity and the variations encountered with different types of trials and institutional environments. A computer Protocol Lifecycle Tracking (PLT) tool would enable study initiation staff to manage the process, and the various clinical research stakeholders to monitor the progress of a study’s initiation, as well as obtain data on the work flow to identify those activities that are in need of operational efficiency improvement. The objective of our work was to develop use cases and system requirements for a PLT tool. The result of our study is a use case document that can serve as the specifications for developing a PLT application

Democratization in a passive dendritic tree : an analytical investigation

One way to achieve amplification of distal synaptic inputs on a dendritic tree is to scale the amplitude and/or duration of the synaptic conductance with its distance from the soma. This is an example of what is often referred to as “dendritic democracy”. Although well studied experimentally, to date this phenomenon has not been thoroughly explored from a mathematical perspective. In this paper we adopt a passive model of a dendritic tree with distributed excitatory synaptic conductances and analyze a number of key measures of democracy. In particular, via moment methods we derive laws for the transport, from synapse to soma, of strength, characteristic time, and dispersion. These laws lead immediately to synaptic scalings that overcome attenuation with distance. We follow this with a Neumann approximation of Green’s representation that readily produces the synaptic scaling that democratizes the peak somatic voltage response. Results are obtained for both idealized geometries and for the more realistic geometry of a rat CA1 pyramidal cell. For each measure of democratization we produce and contrast the synaptic scaling associated with treating the synapse as either a conductance change or a current injection. We find that our respective scalings agree up to a critical distance from the soma and we reveal how this critical distance decreases with decreasing branch radius

A Global Federated Real-World Data and Analytics Platform for Research

Objective This article describes a scalable, performant, sustainable global network of electronic health record data for biomedical and clinical research. Materials and Methods TriNetX has created a technology platform characterized by a conservative security and governance model that facilitates collaboration and cooperation between industry participants, such as pharmaceutical companies and contract research organizations, and academic and community-based healthcare organizations (HCOs). HCOs participate on the network in return for access to a suite of analytics capabilities, large networks of de-identified data, and more sponsored trial opportunities. Industry participants provide the financial resources to support, expand, and improve the technology platform in return for access to network data, which provides increased efficiencies in clinical trial design and deployment. Results TriNetX is a growing global network, expanding from 55 HCOs and 7 countries in 2017 to over 220 HCOs and 30 countries in 2022. Over 19 000 sponsored clinical trial opportunities have been initiated through the TriNetX network. There have been over 350 peer-reviewed scientific publications based on the network’s data. Conclusions The continued growth of the TriNetX network and its yield of clinical trial collaborations and published studies indicates that this academic-industry structure is a safe, proven, sustainable path for building and maintaining research-centric data networks

A Novel Cross-Disciplinary Multi-Institute Approach to Translational Cancer Research: Lessons Learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC)

Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium’s intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer specific biomarkers and encourage collaborative research efforts among the participating centers.Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property/tech transfer agreements, and material transfer agreements that have been approved by each of the member institutions. This was the foundational work that has led to the development of a centralized data warehouse that has met each of the institutions’ IRB/HIPAA standards.Results: Currently, this “virtual biorepository” has over 58,000 annotated samples from 11,467 cancer patients available for research purposes. The clinical annotation of tissue samples is either done manually over the internet or semiautomated batch modes through mapping of local data elements with PCABC common data elements. The database currently holds information on 7188 cases (associated with 9278 specimens and 46,666 annotated blocks and blood samples) of prostate cancer, 2736 cases (associated with 3796 specimens and 9336 annotated blocks and blood samples) of breast cancer and 1543 cases (including 1334 specimens and 2671 annotated blocks and blood samples) of melanoma. These numbers continue to grow, and plans to integrate new tumor sites are in progress. Furthermore, the group has also developed a central web-based tool that allows investigators to share their translational (genomics/proteomics) experiment data on research evaluating potential biomarkers via a central location on the Consortium’s web site.Conclusions: The technological achievements and the statewide informatics infrastructure that have been established by the Consortium will enable robust and efficient studies of biomarkers and their relevance to the clinical course of cancer. Studies resulting from the creation of the Consortium may allow for better classification of cancer types, more accurate assessment of disease prognosis, a better ability to identify the most appropriate individuals for clinical trial participation, and better surrogate markers of disease progression and/or response to therapy

Losing the media battle, waging the policy war: The pharmaceutical industry’s response to the access to medicines crisis in the Global South

This article sheds new light on the pharmaceutical industry’s response to the public relations crisis generated by the global civil society campaign for access to HIV/AIDS medicines since the early 2000s – one of the most contentious policy areas of global trade and health governance. Drawing on interviews with industry insiders, the article explores the industry’s communicative agency in both the media sphere and key sites of power, with a focus on the European Union (EU) policy sphere. The analysis shows that the industry has focused primarily on maintaining access to policymakers and sustaining elite consensus around the existing global intellectual property rights regime through political communication activities that largely bypass mediated public arenas – from strategically promoting its corporate social responsibility (CSR) programmes and mobilizing third-party endorsement to direct lobbying. The article concludes by reflecting on the implications of the findings for critical investigations of the interplay between media and political power in relation to global economic governance

Exploring Breast Cancer Systemic Drug Therapy Patterns in Real-World Data

PURPOSE: To explore medications and their administration patterns in real-world patients with breast cancer. METHODS: A retrospective study was performed using TriNetX, a federated network of deidentified, Health Insurance Portability and Accountability Act-compliant data from 21 health care organizations across North America. Patients diagnosed with breast cancer between January 1, 2013, and May 31, 2022, were included. We investigated a rule-based and unsupervised learning algorithm to extract medications and their administration patterns. To group similar administration patterns, we used three features in k-means clustering: total number of administrations, median number of days between administrations, and standard deviation of the days between administrations. We explored the first three lines of therapy for patients classified into six groups on the basis of their stage at diagnosis (early as stages I-III RESULTS: In early-stage HR+/ CONCLUSION: Although there is a general agreement with the NCCN Guidelines, real-world medication data exhibit variability in the medications and their administration patterns

When to start antiretroviral therapy in resource-limited settings: a human rights analysis

<p>Abstract</p> <p>Background</p> <p>Recent evidence from developed and developing countries shows clear clinical and public health benefit to starting antiretroviral therapy (ART) earlier. While discussions about when to start ART have often focused on the clinical risks and benefits, the main issue is one of fair limit-setting. We applied a human rights framework to assess a policy of early treatment initiation according to the following criteria: public-health purpose; likely effectiveness; specificity; human rights burdens and benefits; potential for less restrictive approaches; and fair administration.</p> <p>Discussion</p> <p>According to our analysis, a policy of earlier ART initiation would better serve both public health and human rights objectives. We highlight a number of policy approaches that could be taken to help meet this aim, including increased international financial support, alternative models of care, and policies to secure the most affordable sources of appropriate antiretroviral drugs.</p> <p>Summary</p> <p>Widespread implementation of earlier ART initiation is challenging in resource-limited settings. Nevertheless, rationing of essential medicines is a restriction of human rights, and the principle of least restriction serves to focus attention on alternative measures such as adapting health service models to increase capacity, decreasing costs, and seeking additional international funding. Progressive realisation using well-defined steps will be necessary to allow for a phased implementation as part of a framework of short-term targets towards nationwide policy adoption, and will require international technical and financial support.</p

Perceived intensity of somatosensory cortical electrical stimulation

Artificial sensations can be produced by direct brain stimulation of sensory areas through implanted microelectrodes, but the perceptual psychophysics of such artificial sensations are not well understood. Based on prior work in cortical stimulation, we hypothesized that perceived intensity of electrical stimulation may be explained by the population response of the neurons affected by the stimulus train. To explore this hypothesis, we modeled perceived intensity of a stimulation pulse train with a leaky neural integrator. We then conducted a series of two-alternative forced choice behavioral experiments in which we systematically tested the ability of rats to discriminate frequency, amplitude, and duration of electrical pulse trains delivered to the whisker barrel somatosensory cortex. We found that the model was able to predict the performance of the animals, supporting the notion that perceived intensity can be largely accounted for by spatiotemporal integration of the action potentials evoked by the stimulus train