MRI-Compatible and Conformal Electrocorticography Grids for Translational Research.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter-sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams. Here, advances in soft neurotechnology are leveraged to manufacture conformable subdural, thin-film ECoG grids, and evaluate their suitability for translational research. Soft grids with 0.2 to 10 mm electrode pitch and diameter are embedded in 150 µm silicone membranes. The soft grids are compatible with surgical handling and can be folded to safely interface hidden cerebral surface such as the Sylvian fold in human cadaveric models. It is found that the thin-film conductor grids do not generate diagnostic-impeding imaging artefacts (<1 mm) nor adverse local heating within a standard 3T clinical magnetic resonance imaging scanner. Next, the ability of the soft grids to record subdural neural activity in minipigs acutely and two weeks postimplantation is validated. Taken together, these results suggest a promising future alternative to current stiff electrodes and may enable the future adoption of soft ECoG grids in translational research and ultimately in clinical settings.

The application of molecular imaging to advance translational research in chronic inflammation.

Over the past several decades, molecular imaging techniques to assess cellular processes in vivo have been integral in advancing our understanding of disease pathogenesis. 18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) imaging in particular has shaped the field of atherosclerosis research by highlighting the importance of underlying inflammatory processes that are responsible for driving disease progression. The ability to assess physiology using molecular imaging, combining it with anatomic delineation using cardiac coronary angiography (CCTA) and magnetic resonance imaging (MRI) and lab-based techniques, provides a powerful combination to advance both research and ultimately clinical care. In this review, we demonstrate how molecular imaging studies, specifically using 18-FDG PET, have revealed that early vascular disease is a systemic process with multiple, concurrent biological mechanisms using inflammatory diseases as a basis to understand early atherosclerotic mechanisms in humans.

Pharmacogenomics Biomarker Discovery and Validation for Translation in Clinical Practice.

Interindividual variability in drug efficacy and toxicity is a major challenge in clinical practice. Variations in drug pharmacokinetics (PKs) and pharmacodynamics (PDs) can be, in part, explained by polymorphic variants in genes encoding drug metabolizing enzymes and transporters (absorption, distribution, metabolism, and excretion) or in genes encoding drug receptors. Pharmacogenomics (PGx) has allowed the identification of predictive biomarkers of drug PKs and PDs and the current knowledge of genome-disease and genome-drug interactions offers the opportunity to optimize tailored drug therapy. High-throughput PGx genotyping, from targeted to more comprehensive strategies, allows the identification of PK/PD genotypes to be developed as clinical predictive biomarkers. However, a biomarker needs a robust process of validation followed by clinical-grade assay development and must comply to stringent regulatory guidelines. We here discuss the methodological challenges and the emerging technological tools in PGx biomarker discovery and validation, at the crossroad among molecular genetics, bioinformatics, and clinical medicine.

Good practices in harnessing social media for scholarly discourse, knowledge translation, and education.

INTRODUCTION: There still remains a gap between those who conduct science and those who engage in educating others about health sciences through various forms of social media. Few empirical studies have sought to define useful practices for engaging in social media for academic use in the health professions. Given the increasing importance of these platforms, we sought to define good practices and potential pitfalls with help of those respected for their work in this new field. METHODS: We conducted a qualitative study, guided by constructivist grounded theory principles, of 17 emerging experts in the field of academic social media. We engaged in a snowball sampling technique and conducted a series of semi-structured interviews. The analytic team consisted of a diverse group of researchers with a range of experience in social media. RESULTS: Understanding the strengths of various platforms was deemed to be of critical importance across all the participants. Key to building online engagement were the following: 1) Culture-building strategies; 2) Tailoring the message; 3) Responsiveness; and 4) Heeding rules of online engagement. Several points of caution were noted within our participants' interviews. These were grouped into caveat emptor and the need for critical appraisal, and common pitfalls when broadcasting one's self. DISCUSSION: Our participants were able to share a number of key practices that are central to developing and sharing educational content via social media. The findings from the study may guide future practitioners seeking to enter the space. These good practices support professionals for effective engagement and knowledge translation without being harmed.

An Innovative Online Knowledge Translation Curriculum in Graduate Education.

BACKGROUND: There is increased acknowledgment of the importance of knowledge translation (KT) in the role of graduate-prepared healthcare practitioners, such as nurses, as change agents in the mobilization of evidence-based knowledge. The offering of flexible educational programming online and hybrid course delivery in higher education is a response to insufficient didactic methods for providing graduate students with the competencies to facilitate KT. AIMS: To describe the development, implementation, and evaluation of a cohort-based, online, innovative KT curriculum using a theoretical approach to KT called the Knowledge-As-Action Framework, which focuses on the knower, knowledge, and context as being inseparable. This process strategically engages with stakeholders to link practice concerns with existing realities, thus providing the best available knowledge to inform KT action in complex healthcare contexts. METHODS: The Model of Evidence-Informed, Context-Relevant, Unified Curriculum Development in Nursing Education guided the cohort-based online KT course process. The development, implementation, and evaluation involved (a) an environmental scan, (b) a literature review, (c) faculty development, (d) curriculum design of two 10-week courses, and (e) a summation of the concurrent participatory evaluation of the two courses, including faculty and student responses. The Knowledge-As-Action Framework is comprised of six interrelated dimensions as part of a "kite" metaphor, with the underlying premise that if any one of the dimensions results in an imbalance, the KT process may be grounded. RESULTS: Evaluation revealed (a) intentionality of the core processes of curriculum work; (b) effectiveness of indicators for evaluating the KT courses; (c) leadership should be added as a learning domain for KT; (d) the Knowledge-As-Action Framework provided an integrated, philosophical, and evidence-based approach to KT; (e) cohort model facilitated a community of inquiry; and (f) the formalized structured approach of the courses with ongoing supervision and mentoring allowed for timely completion. LINKING EVIDENCE TO ACTION: Teaching and learning in an online cohort model created a community of inquiry and facilitated experiential learning. The active engagement of students with their practice-based stakeholders promoted change in clinical settings and enhanced students' professional development to lead change.

From Education to Practice: Incorporating Quality Improvement Projects Into a Baccalaureate Nursing Curriculum.

The accelerated pace of change in health care and the call for a radical transformation in prelicensure nursing education will require changes in baccalaureate nursing programs to ensure nurses are adequately prepared for practice. At one Midwestern university, academic nurse educators developed an innovative multilevel interprofessional and intradisciplinary education opportunity using a Lean Healthcare quality improvement (QI) process to improve systems, strengthen academic-practice partnerships, and bridge the education-to-practice gap. During one 16-week semester, one group of sophomore and junior clinical nursing students worked collaboratively with personnel at a local health care organization on a QI project on sequential compression devices. The students identified practice barriers related to sequential compression device compliance when medication prophylaxis was contraindicated. Using a Lean QI framework, the students developed and implemented a comprehensive, evidence-based venous thromboembolism prophylaxis policy, including tools and strategies for educating employees and patients.

Using Online Survey Software to Enhance Rigor and Efficiency of Knowledge Synthesis Reviews.

With the explosion of scientific literature, information technologies, and the rise of evidence-based health care, methodologies for literature reviews continue to advance. Yet there remains a lack of clarity about techniques to rigorously and efficiently extract and synthesize data from primary sources. We developed a new method for data extraction and synthesis for completing rigorous, knowledge synthesis using freely available online survey software that results in a review-specific, online data extraction, and synthesis tool. The purpose of this paper is to delineate this method using our published integrative review as an exemplar. Although the purpose of online survey software is to obtain and analyze survey responses, these software programs allows for the efficient extraction and synthesize of disparate study features from primary sources. Importantly, use of the method has the potential to increase the rigor and efficiency of published reviews bringing the promise of advancing multiple areas of health science.

General Pediatricians' Performance of Accreditation Agency's Recommended Procedures: A Complementary Analysis Using Administrative Data and the Knowledge Translation Model.

INTRODUCTION: The Accreditation Council for Graduate Medical Education provided guidelines, in 2013, regarding 13 clinical procedures pediatric residents should learn. Previous studies show that, when asked, general pediatricians (GPeds) self-report performing these procedures infrequently. When examined using the knowledge translation model, this low procedural performance frequency, especially by GPeds, may indicate a problem within the primary care landscape. METHODS: This was a descriptive study using the Partners For Kids, an accountable care organization, database to obtain how frequently each of the procedures was performed for a geographically representative sample of GPeds in central Ohio. RESULTS: A total of 296 physicians participated in Partners For Kids. Nearly one-third practiced for more than 15 years (n = 83, 28%) and one-third also lived in a rural region (n = 78, 26.4%). The most commonly billed procedure was administering immunizations (n = 79,292, 92.3%); the least was peripheral intravenous catheter placement (n = 2, 0.002%). Most procedures were completed in the office-based setting. DISCUSSION: General pediatricians in central Ohio do not frequently perform the 13 recommended procedures of Accreditation Council for Graduate Medical Education. Evaluation of this problem using the knowledge translation model shows that potential barriers could be inadequate training during or after residency or more likely that these procedures are not necessary in GPeds' current scope of practice. The next step should be to see, from the practitioner's perspective, what procedures are important to their daily practice. Adapting this knowledge to the local context will help target continuing medical education/continuing professional development interventions.

Social media in knowledge translation and education for physicians and trainees: a scoping review.

INTRODUCTION: The use of social media is rapidly changing how educational content is delivered and knowledge is translated for physicians and trainees. This scoping review aims to aggregate and report trends on how health professions educators harness the power of social media to engage physicians for the purposes of knowledge translation and education. METHODS: A scoping review was conducted by searching four databases (PubMed, Scopus, Embase, and ERIC) for publications emerging between 1990 to March 2018. Articles about social media usage for teaching physicians or their trainees for the purposes of knowledge translation or education were included. Relevant themes and trends were extracted and mapped for visualization and reporting, primarily using the Cook, Bordage, and Schmidt framework for types of educational studies (Description, Justification, and Clarification). RESULTS: There has been a steady increase in knowledge translation and education-related social media literature amongst physicians and their trainees since 1996. Prominent platforms include Twitter (n = 157), blogs (n = 104), Facebook (n = 103), and podcasts (n = 72). Dominant types of scholarship tended to be descriptive studies and innovation reports. Themes related to practice improvement, descriptions of the types of technology, and evidence-based practice were prominently featured. CONCLUSIONS: Social media is ubiquitously used for knowledge translation and education targeting physicians and physician trainees. Some best practices have emerged despite the transient nature of various social media platforms. Researchers and educators may engage with physicians and their trainees using these platforms to increase uptake of new knowledge and affect change in the clinical environment.

Musical educational technology for lactation physiology learning: knowledge translation.

OBJECTIVE: create and validate a musical educational technology for lactation physiology learning for professional training in health. METHOD: methodological study with application of a conceptual framework of Knowledge Translation. In the creation cycle, the knowledge of the physiology of lactation was synthetized in key points to create the lyrics and the melody. In the action cycle, the content of the musical educational technology was validated by judges experts in breast feeding, in the period from September to December 2017. RESULTS: 18 judges from all Brazilian regions participated in the validation. The content of the technology obtained a global Content Validity Index of 0.94 with one round of validation. CONCLUSION: the musical educational technology is validated to introduce the content of the physiology of lactation in the learning process of students, mediated by the teacher.

A translational framework for peripheral nerve stimulating electrodes: Reviewing the journey from concept to clinic.

The purpose of this review article is to describe the underlying methodology for successfully translating novel interfaces for electrical modulation of the peripheral nervous system (PNS) from basic design concepts to clinical applications and chronic human use. Despite advances in technologies to communicate directly with the nervous system, the pathway to clinical translation for most neural interfaces is not clear. FDA guidelines provide information on necessary evidence which should be generated and submitted to allow the agency evaluate safety and efficacy of a new medical device. However, a knowledge gap exists on translating neural interfaces from pre-clinical studies into the clinical domain. Our article is intended to inform the field on some of the key considerations for such a transition process specific to neural interfaces that may not be already covered by FDA guidances. This framework focuses on non-penetrating peripheral nerve stimulating electrodes that have been proven effective for motor and sensory neural prostheses and successfully transitioned from pre-clinical through first-in-human and chronic clinical deployment. We discuss the challenges of moving these neural interfaces along the translational continuum and ultimately through FDA approval for human feasibility studies. Specifically, we describe a translational process involving: quantitative human anatomy, neural modeling and simulation, acute intraoperative testing and verification, clinical demonstration with temporary percutaneous access, and finally chronic clinical deployment and functional performance. To clarify and demonstrate the importance of each step of this translational framework, we present case studies from electrodes developed at Case Western Reserve University (CWRU), specifically the spiral cuff, the Flat Interface Nerve Electrode (FINE), and the Composite FINE (C-FINE). In addition, we demonstrate that success along this translational pathway can be further expedited by: appropriate selection of well-characterized materials, validation of fabrication and sterilization protocols, well-implemented quality control measures, and quantification of impact on neural structure, health, and function. The issues and approaches identified in this review for the peripheral nervous system may also serve to accelerate the dissemination of any new neural interface into clinical practice, and consequently advance the performance, utility, and clinical value of new neural prostheses or neuromodulation systems.

USE: An integrative suite for temporally-precise psychophysical experiments in virtual environments for human, nonhuman, and artificially intelligent agents.

BACKGROUND: There is a growing interest in complex, active, and immersive behavioral neuroscience tasks. However, the development and control of such tasks present unique challenges. NEW METHOD: The Unified Suite for Experiments (USE) is an integrated set of hardware and software tools for the design and control of behavioral neuroscience experiments. The software, developed using the Unity video game engine, supports both active tasks in immersive 3D environments and static 2D tasks used in more traditional visual experiments. The custom USE SyncBox hardware, based around an Arduino Mega2560 board, integrates and synchronizes multiple data streams from different pieces of experimental hardware. The suite addresses three key issues with developing cognitive neuroscience experiments in Unity: tight experimental control, accurate sub-ms timing, and accurate gaze target identification. RESULTS: USE is a flexible framework to realize experiments, enabling (i) nested control over complex tasks, (ii) flexible use of 3D or 2D scenes and objects, (iii) touchscreen-, button-, joystick- and gaze-based interaction, and (v) complete offline reconstruction of experiments for post-processing and temporal alignment of data streams. COMPARISON WITH EXISTING METHODS: Most existing experiment-creation tools are not designed to support the development of video-game-like tasks. Those that do use older or less popular video game engines as their base, and are not as feature-rich or enable as precise control over timing as USE. CONCLUSIONS: USE provides an integrated, open source framework for a wide variety of active behavioral neuroscience experiments using human and nonhuman participants, and artificially-intelligent agents.

The "House of Quality for Behavioral Science"-a user-centered tool to design behavioral interventions.

Within the behavioral field, a plethora of conceptual frameworks and tools have been developed to improve transition from efficacy to effectiveness trials; however, they are limited in their ability to support new, iterative intervention design decision-making methodologies beyond traditional randomized controlled trial design. Emerging theories suggest that researchers should employ engineering based user-centered design (UCD) methods to support more iterative intervention design decision-making in the behavioral field. We present, an adaptation of a UCD tool used in the engineering field-the Quality Function Deployment "House of Quality" correlation matrix, to support iterative intervention design decision-making and documentation for multicomponent behavioral interventions and factorial trial designs. We provide a detailed description of the adapted tool-"House of Quality for Behavioral Science", and a step-by-step use-case scenario to demonstrate the early identification of intervention flaws and prioritization of requirements. Four intervention design flaws were identified via the tool application. Completion of the relationship correlation matrix increased requirement ranking variance for the researcher (σ2 = 0.47 to 7.19) and participant (σ2 = 0.56 to 3.89) perspective. Requirement prioritization (ranking) was facilitated by factoring in the strength of the correlation between each perspective and corresponding importance. A correlational matrix tool such as the "House of Quality for Behavioral Science" may provide a structured, UCD approach that balances researcher and participant needs and identifies design flaws for pragmatic behavioral intervention design. This tool may support iterative design decision-making for multicomponent and factorial trial designs.

Musical educational technology for lactation physiology learning: knowledge translation / Tecnología educativa musical para el aprendizaje de la fisiología de la lactancia: traducción del conocimiento / Tecnologia educativa musical para aprendizagem da fisiologia da lactação: tradução do conhecimento

ABSTRACT Objective: create and validate a musical educational technology for lactation physiology learning for professional training in health. Method: methodological study with application of a conceptual framework of Knowledge Translation. In the creation cycle, the knowledge of the physiology of lactation was synthetized in key points to create the lyrics and the melody. In the action cycle, the content of the musical educational technology was validated by judges experts in breast feeding, in the period from September to December 2017. Results: 18 judges from all Brazilian regions participated in the validation. The content of the technology obtained a global Content Validity Index of 0.94 with one round of validation. Conclusion: the musical educational technology is validated to introduce the content of the physiology of lactation in the learning process of students, mediated by the teacher.

RESUMEN Objetivo: crear y validar una tecnología educativa musical para el aprendizaje de la fisiología de la lactancia en la formación profesional en salud. Método: estudio metodológico con aplicación del Modelo Conceptual de Traducción del Conocimiento. En el ciclo de creación, el conocimiento de la fisiología de la lactancia fue sintetizado en puntos clave con los que se crearon la letra y la melodía. En el ciclo de acción, el contenido de la tecnología educativa musical fue validado por jueces expertos en lactancia materna, en el período de septiembre a diciembre de 2017. Resultados: 18 jueces de todas las regiones brasileñas participaron de la validación. El contenido de la tecnología obtuvo un Índice de Validez de Contenido global de 0.94 con una ronda de evaluación. Conclusión: se validó la tecnología educativa musical para introducir el contenido de la fisiología de la lactancia en el proceso de aprendizaje del alumno, mediado por el profesor.

RESUMO Objetivo: criar e validar uma tecnologia educativa musical para a aprendizagem da fisiologia da lactação na formação profissional em saúde. Método: estudo metodológico com aplicação de Modelo Conceitual de Tradução do Conhecimento. No ciclo de criação foi sintetizado o conhecimento da fisiologia da lactação em pontos-chave, com os quais foram criadas a letra e a melodia. No ciclo de ação foi validado o conteúdo da tecnologia educativa musical por juízes experts em aleitamento materno, no período de setembro a dezembro de 2017. Resultados: 18 juízes de todas as regiões brasileiras participaram da validação. O conteúdo da tecnologia obteve Índice de Validade de Conteúdo global de 0,94 com uma rodada de avaliação. Conclusão: a tecnologia educativa musical está validada para introduzir o conteúdo da fisiologia da lactação no processo de aprendizagem de estudantes, mediado pelo docente.

Clinical Translation of the LevelCheck Decision Support Algorithm for Target Localization in Spine Surgery.

Recent work has yielded a method for automatic labeling of vertebrae in intraoperative radiographs as an assistant to manual level counting. The method, called LevelCheck, previously demonstrated promise in phantom studies and retrospective studies. This study aims to: (#1) Analyze the effect of LevelCheck on accuracy and confidence of localization in two modes: (a) Independent Check (labels displayed after the surgeon's decision) and (b) Active Assistant (labels presented before the surgeon's decision). (#2) Assess the feasibility and utility of LevelCheck in the operating room. Two studies were conducted: a laboratory study investigating these two workflow implementations in a simulated operating environment with 5 surgeons, reviewing 62 cases selected from a dataset of radiographs exhibiting a challenge to vertebral localization; and a clinical study involving 20 patients undergoing spine surgery. In Study #1, the median localization error without assistance was 30.4% (IQR = 5.2%) due to the challenging nature of the cases. LevelCheck reduced the median error to 2.4% for both the Independent Check and Active Assistant modes (p < 0.01). Surgeons found LevelCheck to increase confidence in 91% of cases. Study #2 demonstrated accuracy in all cases. The algorithm runtime varied from 17 to 72 s in its current implementation. The algorithm was shown to be feasible, accurate, and to improve confidence during surgery.

Nonhuman Primate Models of Huntington's Disease and Their Application in Translational Research.

Huntington's disease (HD) is a monogenic, autosomal dominant inherited fatal disease that affects 1 in 10,000 people worldwide. Given its unique genetic characteristics, HD would appear as one of the most straightforward neurodegenerative diseases to replicate in animal models. Indeed, mutations in the HTT gene have been used to generate a variety of animal models that display differential pathologies and have significantly increased our understanding of the pathological mechanisms of HD. However, decades of efforts have also shown the complexity of recapitulating the human condition in other species. Here we describe the three different types of models that have been generated in nonhuman primate species, stating their advantages and limitations and attempt to give a critical perspective of their translational value to test the efficacy of novel therapeutic strategies. Obtaining construct, phenotypic, and predictive validity has proven to be challenging in most animal models of human diseases. In HD in particular, it is hard to assess the predictive validity of a new therapeutic strategy when no effective "benchmark" treatment is available in the clinic. In this light, only phenotypic/face validity and construct validity are discussed.