High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows.

Drug development suffers from a lack of predictive and human-relevant in vitro models. Organ-on-chip (OOC) technology provides advanced culture capabilities to generate physiologically appropriate, human-based tissue in vitro, therefore providing a route to a predictive in vitro model. However, OOC technologies are often created at the expense of throughput, industry-standard form factors, and compatibility with state-of-the-art data collection tools. Here we present an OOC platform with advanced culture capabilities supporting a variety of human tissue models including liver, vascular, gastrointestinal, and kidney. The platform has 96 devices per industry standard plate and compatibility with contemporary high-throughput data collection tools. Specifically, we demonstrate programmable flow control over two physiologically relevant flow regimes: perfusion flow that enhances hepatic tissue function and high-shear stress flow that aligns endothelial monolayers. In addition, we integrate electrical sensors, demonstrating quantification of barrier function of primary gut colon tissue in real-time. We utilize optical access to the tissues to directly quantify renal active transport and oxygen consumption via integrated oxygen sensors. Finally, we leverage the compatibility and throughput of the platform to screen all 96 devices using high content screening (HCS) and evaluate gene expression using RNA sequencing (RNA-seq). By combining these capabilities in one platform, physiologically-relevant tissues can be generated and measured, accelerating optimization of an in vitro model, and ultimately increasing predictive accuracy of in vitro drug screening.

Loss as a determinant of PTSD in a cohort of adult survivors of the 1988 earthquake in Armenia: implications for policy.

OBJECTIVE: To study the relationship of post-traumatic stress disorder (PTSD) to severity of the disaster experience. METHOD: A sample of 1785 adult participants of an epidemiological study initiated in the immediate aftermath of the 1988 earthquake in Armenia were interviewed about 2 years following the disaster based on the NIMH DIS-Disaster Supplement. All 154 cases of pure PTSD were compared with 583 controls without symptoms satisfying psychiatric diagnoses of interest. RESULTS: PTSD cases included more persons from areas with the worst destruction. Having the highest level of education compared to lowest (OR 0.6 [95% CI 0.4-0.9]), being accompanied at the moment of the earthquake (OR 0.6 [95% CI 0.4-0.9]) and making new friends after the earthquake (OR 0.6 [95% CI 0.5-0.8]) were protective for PTSD. PTSD risk increased with the total amount of loss to the family (OR for highest level of loss 4.1 [95% CI 2.3-7.5]). CONCLUSION: Based on this large population sample, we believe that early support to survivors with high levels of loss may reduce PTSD following earthquakes.