Mitigating Space Industry Supply Chain Risk Thru Risk-Based Analysis

Using risk-based analysis to consider supply chain disruptions and uncertainty along with potential mitigation strategies in the early stages of space industry projects can be used avoid schedule delays, cost overruns, and lead to successful project outcomes. Space industry projects, especially launch vehicles, are complicated assemblies of high-technology and specialized components. Components are engineered, procured, manufactured, and assembled for specific missions or projects, unlike make-to-stock manufacturing where assemblies are produced at a mass production rate for customers to choose off the shelf or lot, like automobiles. The supply chain for a space industry project is a large, complicated web where one disruption, especially for sole-sourced components, could ripple through the project causing delays at multiple project milestones. This ripple effect can even cause the delay or cancelation of the entire project unless project managers develop and employ risk mitigations strategies against supply chain disruption and uncertainty. The unpredictability of when delays and disruptions may occur makes managing these projects extremely difficult. By using risk-based analysis, project managers can better plan for and mitigate supply chain risk and uncertainty for space industry projects to better manage project success. Space industry project supply chain risk and uncertainty can be evaluated through risk assessments at major project milestones and during the procurement process. Mitigations for identified risks can be evaluated and implemented to better manage project success. One mitigation strategy to supply chain risk and uncertainty is implementing a dual or multi-supplier sourcing procurement strategy. This research explores using a risk-based analysis to identify where this mitigation strategy can be beneficial for space industry projects and how its implementation affects project success. First a supply chain risk assessment and mitigation decision tool will be used at major project milestones to show where a multi-sourcing strategy may be beneficial. Next, updated supplier quote evaluation tools will confirm the usage of multiple suppliers for procurement. Modeling and simulation are then used to show the impact of that strategy on the project success metrics of cost and schedule

Communication of bed allocation decisions in a critical care unit and accountability for reasonableness

BACKGROUND: Communication may affect perceptions of fair process for intensive care unit bed allocation decisions through its impact on the publicity condition of accountability for reasonableness. METHODS: We performed a qualitative case study to describe participant perceptions of the communication of bed allocation decisions in an 18-bed university affiliated, medical-surgical critical care unit at Sunnybrook and Women's College Health Sciences Centre. Interviewed participants were 3 critical care physicians, 4 clinical fellows in critical care, 4 resource nurses, 4 "end-users" (physicians who commonly referred patients to the unit), and 3 members of the administrative staff. Median bed occupancy during the study period (Jan-April 2003) was 18/18; daily admissions and discharges (median) were 3. We evaluated our description using the ethical framework "accountability for reasonableness" (A4R) to identify opportunities for improvement. RESULTS: The critical care physician, resource nurse, critical care fellow and end-users (trauma team leader, surgeons, neurosurgeons, anesthesiologists) functioned independently in unofficial "parallel tracks" of bed allocation decision-making; this conflicted with the official designation of the critical care physician as the sole authority. Communication between key decision-makers was indirect and could exclude those affected by the decisions; notably, family members. Participants perceived a lack of publicity for bed allocation rationales. CONCLUSION: The publicity condition should be improved for critical care bed allocation decisions. Decision-making in the "parallel tracks" we describe might be unavoidable within usual constraints of time, urgency and demand. Formal guidelines for direct communication between key participants in such circumstances would help to improve the fairness of these decisions

Physical activity and pre-diabetes—an unacknowledged mid-life crisis: findings from NHANES 2003–2006

The prevalence of pre-diabetes (PD) among US adults has increased substantially over the past two decades. By current estimates, over 34% of US adults fall in the PD category, 84% of whom meet the American Diabetes Association’s criteria for impaired fasting glucose (IFG). Low physical activity (PA) and/or sedentary behavior are key drivers of hyperglycemia. We examined the relationship between PD and objectively measured PA in NHANES 2003–2006 of 20,470 individuals, including 7,501 individuals between 20 and 65 yrs.We excluded all participants without IFG measures or adequate accelerometry data (final N = 1,317). Participants were identified as PD if FPG was 100–125 mg/dL (5.6–6.9 mmol/L). Moderate and vigorous PA in minutes/day individuals were summed to create the exposure variable “moderate-vigorous PA” (MVPA). The analysis sample included 884 normoglycemic persons and 433 with PD. There were significantly fewer PD subjects in the middle (30.3%) and highest (24.6%) tertiles of PA compared to the lowest tertile (35.5%). After adjusting for BMI, participants were 0.77 times as likely to be PD if they were in the highest tertile compared to the lowest PA tertile (p < 0.001). However, these results were no longer significant when age and BMI were held constant. Univariate analysis revealed that physical activity was associated with decreased fasting glucose of 0.5 mg/dL per minute of MVPA, but multivariate analysis adjusting for age and BMI was not significant. Overall, our data suggest a negative association between measures of PA and the prevalence of PD in middle-aged US adults independent of adiposity, but with significant confounding influence from measures of BMI and age

AEGIS: Enhancement of Dust-enshrouded Star Formation in Close Galaxy Pairs and Merging Galaxies up to z ~ 1

Using data from the DEEP2 Galaxy Redshift Survey and HST/ACS imaging in the Extended Groth Strip, we select nearly 100 interacting galaxy systems including kinematic close pairs and morphologically identified merging galaxies. Spitzer MIPS 24 micron fluxes of these systems reflect the current dusty star formation activity, and at a fixed stellar mass (M_{*}) the median infrared luminosity (L_{IR}) among merging galaxies and close pairs of blue galaxies is twice (1.9 +/- 0.4) that of control pairs drawn from isolated blue galaxies. Enhancement declines with galaxy separation, being strongest in close pairs and mergers and weaker in wide pairs compared to the control sample. At z ~ 0.9, 7.1% +/- 4.3% of massive interacting galaxies (M_{*} > 2*10^{10} M_{solar}) are found to be ULIRGs, compared to 2.6% +/- 0.7% in the control sample. The large spread of IR luminosity to stellar mass ratio among interacting galaxies suggests that this enhancement may depend on the merger stage as well as other as yet unidentified factors (e.g., galaxy structure, mass ratio, orbital characteristics, presence of AGN or bar). The contribution of interacting systems to the total IR luminosity density is moderate (<= 36 %).Comment: 12 pages, 2 figures, 1 table, minor changes to match the proof version, accepted for publication in the ApJL AEGIS Special Issu

The DEEP3 Galaxy Redshift Survey: The Impact of Environment on the Size Evolution of Massive Early-type Galaxies at Intermediate Redshift

Using data drawn from the DEEP2 and DEEP3 Galaxy Redshift Surveys, we investigate the relationship between the environment and the structure of galaxies residing on the red sequence at intermediate redshift. Within the massive (10 < log(M*/Msun) < 11) early-type population at 0.4 < z <1.2, we find a significant correlation between local galaxy overdensity (or environment) and galaxy size, such that early-type systems in higher-density regions tend to have larger effective radii (by ~0.5 kpc or 25% larger) than their counterparts of equal stellar mass and Sersic index in lower-density environments. This observed size-density relation is consistent with a model of galaxy formation in which the evolution of early-type systems at z < 2 is accelerated in high-density environments such as groups and clusters and in which dry, minor mergers (versus mechanisms such as quasar feedback) play a central role in the structural evolution of the massive, early-type galaxy population.Comment: 11 pages, 5 figures, 2 tables; resubmitted to MNRAS after addressing referee's comments (originally submitted to journal on August 16, 2011

The Evolution of Galaxy Mergers and Morphology at z<1.2 in the Extended Groth Strip

We present the quantitative rest-frame B morphological evolution and galaxy merger fractions at 0.2 < z < 1.2 as observed by the All-wavelength Extended Groth Strip International Survey (AEGIS). We use the Gini coefficent and M_20 to identify major mergers and classify galaxy morphology for a volume-limited sample of 3009 galaxies brighter than 0.4 L_B^*, assuming pure luminosity evolution of 1.3 M_B per unit redshift. We find that the merger fraction remains roughly constant at 10 +/- 2% for 0.2 < z < 1.2. The fraction of E/S0/Sa increases from 21+/- 3% at z ~ 1.1 to 44 +/- 9% at z ~ 0.3, while the fraction of Sb-Ir decreases from 64 +/- 6% at z ~ 1.1 to 47 +/- 9% at z ~ 0.3. The majority of z 10^11 L_sun are disk galaxies, and only ~ 15% are classified as major merger candidates. Edge-on and dusty disk galaxies (Sb-Ir) are almost a third of the red sequence at z ~ 1.1, while E/S0/Sa makeup over 90% of the red sequence at z ~ 0.3. Approximately 2% of our full sample are red mergers. We conclude (1) the galaxy merger rate does not evolve strongly between 0.2 < z < 1.2; (2) the decrease in the volume-averaged star-formation rate density since z ~ 1 is a result of declining star-formation in disk galaxies rather than a disappearing population of major mergers; (3) the build-up of the red sequence at z < 1 can be explained by a doubling in the number of spheroidal galaxies since z ~ 1.2.Comment: 24 pages, including 3 tables and 18 color figures; accepted to the Astrophysical Journal; high resolution version available at http://www.noao.edu/noao/staff/lotz/lotz_mergers.pd

Rapid translation of clinical guidelines into executable knowledge : a case study of COVID-19 and online demonstration

Introduction: We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID‐19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020. Methods: The PROforma guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID‐19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice. Results: PROforma and OpenClinical.net proved to be an effective combination for rapidly creating the COVID‐19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746. Conclusions: This is believed to be the first use of AI/knowledge engineering methods for disseminating best‐practice in COVID‐19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare

Factors Associated with Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported RTOG trials of concurrent chemoradiotherapy for locally advanced SCCHN (RTOG 91-11; 97-03; and 99-14). Severe late toxicity was defined in this secondary analysis as chronic Grade 3-4 pharyngeal/laryngeal toxicity (RTOG/EORTC late toxicity scoring system) and/or requirement for a feeding tube ≥2 years after registration and/or potential treatment-related death (e.g. pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pre-treatment and treatment potential factors. Results A total of 230 patients were evaluable for this analysis, 99 cases (patients with severe late toxicities) and 131 controls; thus 43% of evaluable patients had a severe late toxicity. On multivariable analysis, significant variables correlated with the development of severe late toxicity were older age (odds ratio 1.05 per year; p = 0.001); advanced T-stage (odds ratio 3.07; p=0.0036); larynx/hypopharynx primary site (odds ratio 4.17; p=0.0041); and neck dissection after chemo-RT (odds ratio 2.39; p=0.018). Conclusions Severe late toxicity following CCRT is common. Older age, advanced T-stage, and larynx/ hypopharynx primary site were strong independent risk American Society of Clinical Oncology. Machtay, M. et al: J. Clin. Oncol. 26 (21), 2008:3582-3589

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion.

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance