No abstract

Tissue extracellular matrix (ECM) is a structurally and compositionally unique microenvironment within which native cells can perform their natural biological activities. Cells grown on artificial substrata differ biologically and phenotypically from those grown within their native tissue microenvironment. Studies examining human tissue ECM structures and the biology of human tissue cells in their corresponding tissue ECM are lacking. Such investigations will improve our understanding about human pathophysiological conditions for better clinical care. We report here human normal breast tissue and invasive ductal carcinoma tissue ECM structural features. For the first time, a hydrogel was successfully fabricated using whole protein extracts of human normal breast ECM. Using immunofluorescence staining of type I collagen (Col I) and machine learning of its fibrous patterns in the polymerized human breast ECM hydrogel, we have defined the microstructural characteristics of the hydrogel and compared the microstructures with those of other native ECM hydrogels. Importantly, the ECM hydrogel supported 3D growth and cell-ECM interaction of both normal and cancerous mammary epithelial cells. This work represents further advancement toward full reconstitution of the human breast tissue microenvironment, an accomplishment that will accelerate the use of human pathophysiological tissue-derived matrices for individualized biomedical research and therapeutic development.

Modeling human breast tissue architecture is essential to study the pathophysiological conditions of the breast. We report that normal mammary epithelial cells grown in human breast extracellular matrix (ECM) hydrogel formed acini structurally similar to those of human and pig mammary tissues. Type I, II, III and V collagens were commonly identified in human, pig, and mouse breast ECM. Mammary epithelial cells formed acini on certain types or combinations of the four collagens at normal levels of breast tissue elasticity. Comparison of the collagen species in mouse normal breast and breast tumor ECM revealed common and distinct sets of collagens within the two types of tissues. Elevated expression of collagen type I alpha 1 chain (Col1a1) was found in mouse and human breast cancers. Collagen type XXV alpha 1 chain (Col25a1) was identified in mouse breast tumors but not in normal breast tissues. Our data provide strategies for modeling human breast pathophysiological structures and functions using native tissue-derived hydrogels and offer insight into the potential contributions of different collagen types in breast cancer development.

Introduction Safety performance indicators (SPIs) are used in aviation to determine if a trip that is non-compliant with federal regulations is safe to fly. Exemptions to regulations can be granted if a safety case demonstrates that the SPIs for an alternative means of compliance (AMOC; i.e., a trip outside regulations) are non-inferior to SPIs for a safety standard operation (SSO; i.e. a trip compliant with regulations). Through this process, it has previously been suggested that ultra-long-range flights are non-inferior to long-range flights due to increased sleep opportunity. We determined whether SPIs for non-compliant ultra-long-range (ULR) trips are non-inferior to those for compliant short-haul (SH) trips. Methods Performance, fatigue, and sleepiness were assessed at the top of descent (TOD) of flight segments using the Psychomotor Vigilance Task (PVT), Samn-Perelli (SP) fatigue scale, and Karolinska Sleepiness Scale (KSS), respectively. Data were analyzed using non-inferiority testing. Two different ULR trips with different TOD times (ULR trip 1: n=81; ULR trip 2: n=22) were compared to two types of SH trips, including one trip that contained one or more all-night flights (SH trip 1: n=48) and one trip with zero all-night flights (SH trip 2: n=47). Results Non-inferiority was found for the SPIs at most comparison points. For example, comparing the SPIs for ULR trip 2 and SH trip 1 at final TOD, non-inferiority was found for all SPIs. In contrast, comparing the SPIs for ULR trip 1 and SH trip 1 at final TOD, non-inferiority was found for SP and KSS, while non-inferiority for PVT was only suggested. Conclusion The findings suggest that the AMOC trips are as safe as or safer than the compliant SH trips. This raises questions regarding the structure of SH trips and how differences in the structures play a role in performance, fatigue and sleepiness. Support United Airlines

Introduction Prior simulation and operational studies have started to address whether the number of consecutive flight segments negatively affects cognitive performance, fatigue, and sleepiness, without reaching a clear consensus. This study expands this literature by determining whether there are significant changes in cognitive performance, fatigue, and sleepiness at critical phases of flight across multiple flight segments, while accounting for the number of segments, flight direction, trip day, and time-of-day. Methods Fifty commercial airline pilots were studied. Each pilot flew two separate short-haul trips, each ranging from 1–4 days and 1–10 flight segments. Cognitive performance, fatigue, and sleepiness were assessed at top-of-climb (TOC) and top-of-descent (TOD) of each flight segment and each trip day. Cognitive performance, fatigue, and sleepiness were assessed using Psychomotor Vigilance Task (PVT) speed, Samn-Perelli (SP) ratings, and Karolinska Sleepiness Scale (KSS) ratings, respectively. Data were analyzed using Wilcoxon t-tests and verified using ANOVAs. Results Mean PVT speed (Cohen’s d =0.57), SP ratings (Cohen’s d = 0.73), and KSS ratings (Cohen’s d = 0.63) were significantly worse at TOD than TOC (p < 0.001); and, significantly varied across flight segments (p<0.001). Cognitive performance, fatigue, and sleepiness were consistently and significantly degraded around the fifth flight segment, improved around the sixth to eighth flights segments, and were subsequently degraded around the eighth to tenth flight segments. Conclusion The results indicate that cognitive performance, fatigue, and sleepiness vary across flight segments, trip day, and phase of flight. Results suggest that these safety performance indices degrade after five segments, and further degrade after eight flight segments. The results presented could be used to inform future airline scheduling and regulation. Support This work has been supported by United Airlines.