Optimizing biomedical discoveries as an engine of culture change in an academic medical center.

Academic discovery in biomedicine is a growing enterprise with tens of billions of dollars in research funding available to universities and hospitals. Protecting and optimizing the resultant intellectual property is required in order for the discoveries to have an impact on society. To achieve that, institutions must create a multidisciplinary, collaborative system of review and support, and utilize connections to industry partners. In this study, we outline the efforts of Case Western Reserve University, coordinated through its Clinical and Translational Science Collaborative (CTSC), to promote entrepreneurial culture, and achieve goals of product development and startup formation for biomedical and population health discoveries arising from the academic ecosystem in Cleveland. The CTSC Office of Translation and Innovation, with the university's Technology Transfer Office (TTO), helps identify and derisk promising IP while building interdisciplinary project teams to optimize the assets through key preclinical derisking steps. The benefits of coordinating funding across multiple programs, assuring dedicated project management to oversee optimizing the IP, and ensuring training to help improve proposals and encourage an entrepreneurial culture, are discussed in the context of a case study of therapeutic assets, the Council to Advance Human Health. This case study highlights best practices in academic innovation.

A new and improved electric fish finder with resources for printed circuit board fabrication

We describe the circuit design, construction, and operation of a field-portable electric fish finder (an AC-coupled wide-band differential bio-amplifier with loudspeaker output). This device permits detection and monitoring of the electric organ discharges generated by neotropical gymnotiform fishes (as well as the mormyroid fishes of tropical Africa). Our design is modified from earlier versions to optimize detection performance and stability over a wider range of ambient water conductivity, including under conditions of extremely low conductivity (< ca. 10 μScm-1). Our new electric fish finder design also incorporates complete waterproofing and longer battery autonomy. We provide Gerber and Eagle files made with the electronic design automation software 'Autodesk Eagle' to allow researchers to order printed circuit boards directly from commercial manufacturers.(AU)

Nós descrevemos o projeto de circuitos eletrônicos e as instrucões para a construção e uso de um detector de peixes elétricos portátil (bio-amplificador diferencial de banda-larga com acoplamento AC). Este aparelho permite a detecção e o monitoramento das descargas de órgãos elétricos gerados por peixes neotropicais da ordem Gymnotiformes (assim como dos peixes mormirídeos da África Tropical). Nosso projeto é modificado a partir de versões anteriores para otimizar o desempenho e a estabilidade sob uma faixa de condutividades ambientais mais ampla, incluindo condições de condutividade extremamente baixa (< ca. 10 μScm-1). Nosso detector de peixes elétricos novo também foi otimizado a fim de proporcionar impermeabilização completa e vida longa para as baterias. Nós fornecemos arquivos 'Gerber' e 'Eagle' preparados com o software de automação de projeto eletrônico 'Autodesk Eagle' para permitir aos pesquisadores a possibilidade de efetuar encomendas de nossa placa de circuito impresso direitamente das empresas de fabricação.(AU)

Comparative Evaluation of Potentially Radiolucent Projectile Components by Radiographs and Computed Tomography.

Projectile components that are traditionally radiolucent can be of considerable importance in determination of weapon type and caliber, but they are often missed on evaluation of postmortem radiographs. We hypothesized that these components would be significantly better visualized by evaluation of computed tomography (CT) scans compared to the practice standard of radiography alone. In this project, potentially radiolucent projectile components were both pulled apart and fired, and the radiolucent components were recovered. These components were embedded in blocks of ballistics gelatin and were imaged using both radiography and CT. The scans were evaluated by three blinded, board-certified radiologists for the presence/absence of projectile components and true-negative regions in each block. If a radiologist indicated visualization of a projectile component, they were further requested to describe their observation. It was found that traditionally radiolucent projectile components are not significantly more often identified on CT scans than radiography (p < 0.05).

A randomized controlled study to evaluate the effect of bexarotene on amyloid-ß and apolipoprotein E metabolism in healthy subjects.

INTRODUCTION: We conducted a phase Ib proof of mechanism trial to determine whether bexarotene (Targretin) increases central nervous system (CNS) apolipoprotein E (apoE) levels and alters Aß metabolism in normal healthy individuals with the APOE ε3/ε3 genotype. METHODS: We used stable isotope labeling kinetics (SILK-ApoE and SILK-Aß) to measure the effect of bexarotene on the turnover rate of apoE and Aß peptides and stable isotope spike absolute quantitation (SISAQ) to quantitate their concentrations in the cerebrospinal fluid (CSF). Normal subjects were treated for 3 days with bexarotene (n = 3 women, 3 men, average 32 years old) or placebo (n = 6 women, average 30.2 years old) before administration of C13-leucine and collection of plasma and CSF over the next 48 hours. Bexarotene concentrations in plasma and CSF were also measured. RESULTS: Oral administration of bexarotene resulted in plasma levels of 1 to 2 µM; however, only low nM levels were found in CSF. Bexarotene increased CSF apoE by 25% but had no effect on metabolism of Aß peptides. DISCUSSION: Bexarotene has poor CNS penetration in normal human subjects. Drug treatment resulted in a modest increase in CSF apoE levels. The absence of an effect on Aß metabolism is likely reflective of the low CNS levels of bexarotene achieved. This study documents the utility of SILK-ApoE technology in measuring apoE kinetics in humans. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov (NCT02061878).