Mammalian artificial chromosomes (MACs) provide a means to introduce large payloads of genetic information into the cell in an autonomously replicating, non-integrating format. Unique among MACs, the mammalian satellite DNA-based Artificial Chromosome Expression (ACE) can be reproducibly generated de novo in cell lines of different species and readily purified from the host cells' chromosomes. Purified mammalian ACEs can then be re-introduced into a variety of recipient cell lines where they have been stably maintained for extended periods in the absence of selective pressure. In order to extend the utility of ACEs, we have established the ACE System, a versatile and flexible platform for the reliable engineering of ACEs. The ACE System includes a Platform ACE, containing >50 recombination acceptor sites, that can carry single or multiple copies of genes of interest using specially designed targeting vectors (ATV) and a site-specific integrase (ACE Integrase). Using this approach, specific loading of one or two gene targets has been achieved in LMTK(-) and CHO cells. The use of the ACE System for biological engineering of eukaryotic cells, including mammalian cells, with applications in biopharmaceutical production, transgenesis and gene-based cell therapy is discussed.
In March 2010, the Environmental Protection Agency (EPA) collaborated with government and nongovernmental organizations to host a groundbreaking symposium, "Strengthening Environmental Justice Research and Decision Making: A Symposium on the Science of Disproportionate Environmental Health Impacts." The symposium provided a forum for discourse on the state of scientific knowledge about factors identified by EPA that may contribute to higher burdens of environmental exposure or risk in racial/ethnic minorities and low-income populations. Also featured were discussions on how environmental justice considerations may be integrated into EPA's analytical and decision-making frameworks and on research needs for advancing the integration of environmental justice into environmental policymaking. We summarize key discussions and conclusions from the symposium and briefly introduce the articles in this issue.
Health systems are struggling to manage a fluctuating volume of critically ill patients with COVID-19 while continuing to provide basic surgical services and expand capacity to address operative cases delayed by the pandemic. As we move forward through the next phases of the pandemic, we will need a decision-making system that allows us to remain nimble as clinicians to meet our patient’s needs while also working with a new framework of healthcare operations. Here, we present our quality improvement process for the adaptation and application of the Medically Necessary Time-Sensitive (MeNTS) toolto gynecologic surgical services beyond the initial COVID response and into recovery of surgical services; with analysis of the reliability of the modified-MeNTS tool in our multi-site safety net hospital network. This multicenter study evaluated the gynecology surgical case volume at three tertiary acute care safety net institutions within the LA County Department of Health Services: Harbor-UCLA (HUMC), Olive View Medical Center (OVMC), and Los Angeles County + University of Southern California (LAC+USC). We describe our modified-Delphi approach to adapt the MeNTS tool in a structured fashion and its application to gynecologic surgical services. Blinded reviewers engaged in a three-round iterative adaptation and final scoring utilizing the modified tool. The cohort consisted of 392 female consecutive gynecology patients across three Los Angeles County Hospitals awaiting scheduled procedures in the surgical queue.The majority of patients were Latina (74.7%) and premenopausal (67.1%). Over half (52.4%) of the patients had cardiovascular disease, while 13.0% had lung disease, and 13.8% had diabetes. The most common indications for surgery were abnormal uterine bleeding (33.2%), pelvic organ prolapse (19.6%) and presence of an adnexal mass (14.3%). Minimally invasive approaches via laparoscopy, robotic-assisted laparoscopy, or vaginal surgery was the predominant planned surgical route (54.8%). Modified-MeNTS scores assumed a normal distribution across all patients within our cohort (Median 33, Range 18–52). Overall, ICC across all three institutions demonstrated “good” interrater reliability (0.72). ICC within institutions at HUMC and OVMC were categorized as “good” interrater reliability, while LAC-USC interrater reliability was categorized as “excellent” (HUMC 0.73, OVMC 0.65, LAC+USC 0.77). The modified-MeNTS tool performed well across a range of patients and procedures with a normal distribution of scores and high reliability between raters. We propose that the modified-MeNTS framework be considered as it employs quantitative methods for decision-making rather than subjective assessments.
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