Building Research Infrastructure to Develop Greater Learning Efficiencies (BRIDGE).

In this manuscript, we outline our developed version of a Learning Health System (LHS) in oncology implemented at the Department of Veterans Affairs (VA). Transferring healthcare into an LHS framework has been one of the spearpoints of VA's Central Office and given the general lack of evidence generated through randomized control clinical trials to guide medical decisions in oncology, this domain is one of the most suitable for this change. We describe our technical solution, which includes a large real-world data repository, a data science and algorithm development framework, and the mechanism by which results are brought back to the clinic and to the patient.

Matching Patients to Accelerate Clinical Trials (MPACT): Enabling Technology for Oncology Clinical Trial Workflow.

Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process.

Beyond mindfulness: Arousal-driven modulation of attentional control during arousal-based practices.

Here we report meditative techniques, which modulate attentional control by arousal-driven influences and not by monitoring continuous thought processes as during mindfulness-related practices. We focus on Vajrayana (Tantric Buddhism) practices, during which a sequence of generation (self-visualization as a deity - Yidam) or completion with sign (inner heat -Tummo) stages necessarily precedes non-dual awareness (NDA) Tantric Mahamudra. We compared the electrocardiographic and electroencephalographic correlates of Mahamudra performed after rest (non-Tantric Mahamudra) with Mahamudra performed after Yidam (Tantric Mahamudra) in 16 highly experienced Vajrayana practitioners, 10 of whom also performed Tummo.

Subcutaneous sarilumab for the treatment of hospitalized patients with moderate to severe COVID19 disease: A pragmatic, embedded randomized clinical trial.

Importance And Objective: The aim of this pragmatic, embedded, adaptive trial was to measure the effectiveness of the subcutaneous anti-IL-6R antibody sarilumab, when added to an evolving standard of care (SOC), for clinical management of inpatients with moderate to severe COVID-19 disease.

Design: Two-arm, randomized, open-label controlled trial comparing SOC alone to SOC plus sarilumab. The trial used a randomized play-the-winner design and was fully embedded within the electronic health record (EHR) system.

Rapid implementation of a modular clinical trial informatics solution for COVID-19 research.

Veterans Health Administration (VHA) services are most frequently used by patients 65 years and older, an age group that is disproportionally affected by COVID-19. Here we describe a modular Clinical Trial Informatics Solution (CTIS) that was rapidly developed and deployed to support a multi-hospital embedded pragmatic clinical trial in COVID-19 patients within the VHA. Our CTIS includes tools for patient eligibility screening, informed consent tracking, treatment randomization, EHR data transformation for reporting and interfaces for patient outcome and adverse event tracking.

ProjectFlow: a configurable workflow management application for point of care research.

Objective: To best meet our point-of-care research (POC-R) needs, we developed ProjectFlow, a configurable, clinical research workflow management application. In this article, we describe ProjectFlow and how it is used to manage study processes for the Diuretic Comparison Project (DCP) and the Research Precision Oncology Program (RePOP).

Materials And Methods: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States.

The Veterans Precision Oncology Data Commons: Transforming VA data into a national resource for research in precision oncology.

The Department of Veterans Affairs (VA) has a strong track record providing high-quality, evidence-based care to cancer patients. In order to accelerate discoveries that will further improve care for Veterans with cancer, the VA has partnered with the Center for Translational Data Science at the University of Chicago and the Open Commons Consortium to establish a data sharing platform, the Veterans Precision Oncology Data Commons (VPODC). The VPODC makes clinical, genomic, and imaging data from the VA available to the research community at large.

Spatio-temporal mapping cortical neuroplasticity in carpal tunnel syndrome.

Neuroimaging data demonstrate that carpal tunnel syndrome, a peripheral neuropathy, is accompanied by maladaptive central neuroplasticity. To further investigate this phenomenon, we collected magnetoencephalography data from 12 patients with carpal tunnel syndrome and 12 healthy control subjects undergoing somatosensory stimulation of the median nerve-innervated Digits 2 and 3, as well as Digit 5, which is innervated by the ulnar nerve. Nerve conduction velocity and psychophysical data were acquired to determine whether standard clinical measures correlated with brain response.

Understanding Immersivity: Image Generation and Transformation Processes in 3D Immersive Environments.

Most research on three-dimensional (3D) visual-spatial processing has been conducted using traditional non-immersive 2D displays. Here we investigated how individuals generate and transform mental images within 3D immersive (3DI) virtual environments, in which the viewers perceive themselves as being surrounded by a 3D world. In Experiment 1, we compared participants' performance on the Shepard and Metzler (1971) mental rotation (MR) task across the following three types of visual presentation environments; traditional 2D non-immersive (2DNI), 3D non-immersive (3DNI - anaglyphic glasses), and 3DI (head mounted display with position and head orientation tracking).

Differences in cortical response to acupressure and electroacupuncture stimuli.

Background: FMRI studies focus on sub-cortical effects of acupuncture stimuli. The purpose of this study was to assess changes in primary somatosensory (S1) activity over the course of different types of acupuncture stimulation. We used whole head magnetoencephalography (MEG) to map S1 brain response during 15 minutes of electroacupuncture (EA) and acupressure (AP).

Brain encoding of acupuncture sensation--coupling on-line rating with fMRI.

Acupuncture-induced sensations have historically been associated with clinical efficacy. These sensations are atypical, arising from sub-dermal receptors, and their neural encoding is not well known. In this fMRI study, subjects were stimulated at acupoint PC-6, while rating sensation with a custom-built, MR-compatible potentiometer.

Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture.

Acupuncture modulation of activity in the human brainstem is not well known. This structure is plagued by physiological artifact in neuroimaging experiments. In addition, most studies have used short (<15 min) block designs, which miss delayed responses following longer duration stimulation.

Spatiotemporal mapping the neural correlates of acupuncture with MEG.

Acupuncture is an ancient Eastern healing modality with putative therapeutic applications. Unfortunately, little is known about the central mechanisms by which acupuncture may exert its effects. In this study, 16 [corrected] healthy subjects were evaluated with magnetoencephalography (MEG) to map the location and timing of brain activity during low-frequency electroacupuncture (EA) and mechanical, noninsertive, sham acupuncture (SA) given at acupoint PC-6.

Brain correlates of autonomic modulation: combining heart rate variability with fMRI.

The central autonomic network (CAN) has been described in animal models but has been difficult to elucidate in humans. Potential confounds include physiological noise artifacts affecting brainstem neuroimaging data, and difficulty in deriving non-invasive continuous assessments of autonomic modulation. We have developed and implemented a new method which relates cardiac-gated fMRI timeseries with continuous-time heart rate variability (HRV) to estimate central autonomic processing.

Acupuncture modulates resting state connectivity in default and sensorimotor brain networks.

Previous studies have defined low-frequency, spatially consistent networks in resting fMRI data which may reflect functional connectivity. We sought to explore how a complex somatosensory stimulation, acupuncture, influences intrinsic connectivity in two of these networks: the default mode network (DMN) and sensorimotor network (SMN). We analyzed resting fMRI data taken before and after verum and sham acupuncture.

Neuroimaging acupuncture effects in the human brain.

Acupuncture is an ancient East Asian healing modality that has been in use for more than 2000 years. Unfortunately, its mechanisms of action are not well understood, and controversy regarding its clinical efficacy remains. Importantly, acupuncture needling often evokes complex somatosensory sensations and may modulate the cognitive/affective perception of pain, suggesting that many effects are supported by the brain and extending central nervous system (CNS) networks.

Do the neural correlates of acupuncture and placebo effects differ?

The neurophysiological basis of therapeutic acupuncture is not well understood but is likely to consist of both specific and non-specific (e.g. placebo) effects.

Spatiotemporal cortical dynamics underlying abstract and concrete word reading.

The current study used whole-head anatomically constrained magnetoencephalography (aMEG) to spatiotemporally map brain responses while subjects made abstract/concrete judgments on visually presented words. Both word types evoked a similar posterior-to-anterior sequence of cortical recruitment involving occipital, temporal, parietal, and frontal areas from approximately 100 to 900 ms poststimulus. A prominent left temporofrontal N400m was smaller to abstract words, while the right temporal N400m was smaller to concrete words, suggesting that differences may exist in their semantic representation.

Automated brainstem co-registration (ABC) for MRI.

Group data analysis in brainstem neuroimaging is predicated on accurate co-registration of anatomy. As the brainstem is comprised of many functionally heterogeneous nuclei densely situated adjacent to one another, relatively small errors in co-registration can manifest in increased variance or decreased sensitivity (or significance) in detecting activations. We have devised a 2-stage automated, reference mask guided registration technique (Automated Brainstem Co-registration, or ABC) for improved brainstem co-registration.

Spatiotemporal brain maps of delayed word repetition and recognition.

Whole-head magnetoencephalography (MEG) was used to spatiotemporally map the brain response underlying episodic retrieval of words studied a single time following a long delay (approximately 40 min). Recognition following a long delay occurs as a strong, sustained, differential response, within bilateral, ventral, and lateral prefrontal cortex, anterior temporal and medial parietal regions from approximately 500 ms onward, as well as ventral occipitotemporal regions from approximately 700 ms onward. In comparison with previous tasks using multiple repetitions at short delays, these effects were centered within the same areas (anteroventral temporal and ventral prefrontal) but were shifted to longer latencies (approximately 500 ms vs.

Spatiotemporal maps of past-tense verb inflection.

Does the brain inflect verbs by applying rules, by associative retrieval of the inflected form, or both? We used whole-head magnetoencephalography to spatiotemporally map the brain response underlying verb past-tense inflection. Placing either regular or irregular verbs into the past tense sequentially modulates the bilateral visual, left inferotemporal, posterior superior temporal (Wernicke's area), left inferior prefrontal (Broca's area), and right prefrontal cortices. Although irregular and regular verb inflection evokes similar cortical response patterns, differences in specific frontotemporal regions are observed.

Spatiotemporal dynamics of modality-specific and supramodal word processing.

The ability of written and spoken words to access the same semantic meaning provides a test case for the multimodal convergence of information from sensory to associative areas. Using anatomically constrained magnetoencephalography (aMEG), the present study investigated the stages of word comprehension in real time in the auditory and visual modalities, as subjects participated in a semantic judgment task. Activity spread from the primary sensory areas along the respective ventral processing streams and converged in anterior temporal and inferior prefrontal regions, primarily on the left at around 400 ms.

N400-like magnetoencephalography responses modulated by semantic context, word frequency, and lexical class in sentences.

Words have been found to elicit a negative potential at the scalp peaking at approximately 400 ms that is strongly modulated by semantic context. The current study used whole-head magnetoencephalography (MEG) as male subjects read sentences ending with semantically congruous or incongruous words. Compared with congruous words, sentence-terminal incongruous words consistently evoked a large magnetic field over the left hemisphere, peaking at approximately 450 ms.