The design and characterization of a next generation microfluidic device for in vitro modeling of bilayer tissue constructs

Advanced tissue culture platforms harness microfabrication techniques and properties of biocompatible materials to create tunable and physiologically-relevant microenvironments. Traditional in vitro tissue models are restricted to flat, static culture plates, which allow for high-throughput experimentation but do not support physiological tissue function. Early research investigates cell response to physiological mechanical cues[1–3], but these devices are largely confined to materials like PDMS[4] or have too low throughput for industry use. The next generation of platforms will combine mechanical cues and integrated sensing with materials that are biologically inert and compatible with high throughput assays and large scale manufacturing, while remaining in an industry-standard footprint. This work represents the design, process development, manufacturing, and characterization of such a system. A microfluidic device manufacturing process was developed to translate the Draper PDMS bilayer microfluidic device[5–7] into a next generation system entirely made of hard plastic. Cyclic olefin copolymer (COC) and polycarbonate thermoplastics were characterized and chosen for their compatibility with drug development applications and large scale manufacturing processes. Hot embossing and thermal bonding procedures were developed that resulted in minimal feature deformation and a robust bond between material layers. Integrated electrical sensors were fabricated in microfluidic channels to quantify transepithelial electrical resistance (TEER) in real time. The sensor design and complex trace routing were demonstrated to be continuous, conductive and fully integrated in the next generation system. The culmination of these design decisions resulted in a hard plastic, bilayer microfluidic device with integrated sensors that is compatible with the industry-standard footprint suited for applications in drug development and disease modeling

What Do Youth Service Librarians Need? Reassessing Goals and Curricula in the Context of Changing Information Needs and Behaviors of Youth

The ALISE Youth Services Special Interest Group (SIG) presents a panel that explores what “youth services” means in the context of LIS education today, including novel additions to youth services curricula and how the changing needs of youth impact LIS education. The session begins with five research presentations, followed by an open discussion and Q&A. The five presentations incorporate the following topics: critical youth information needs, methods of incorporating design thinking and interdisciplinary research into MLIS youth services courses, an investigation of dialogue between librarians and youth, and the role of family and community in youth information behavior. The discussion prompted by this scholarship serves as an important contribution to the continued reform and evolution of youth services education

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease