Assessing Potential Energy Savings in Household Travel: Methodological and Empirical Considerations of Vehicle Capability Constraints and Multi-day Activity Patterns.

The lack of multi-day data for household travel and vehicle capability requirements is an impediment to evaluations of energy savings strategies, since 1) travel requirements vary from day-to-day, and 2) energy-saving transportation options often have reduced capability. This work demonstrates a survey methodology and modeling system for evaluating the energy-savings potential of household travel, considering multi-day travel requirements and capability constraints imposed by the available transportation resources. A stochastic scheduling model is introduced – the multi-day Household Activity Schedule Estimator (mPHASE) – which generates synthetic daily schedules based on “fuzzy” descriptions of activity characteristics using a finite-element representation of activity flexibility, coordination among household members, and scheduling conflict resolution. Results of a thirty-household pilot study are presented in which responses to an interactive computer assisted personal interview were used as inputs to the mPHASE model in order to illustrate the feasibility of generating complex, realistic multi-day household schedules. Study vehicles were equipped with digital cameras and GPS data acquisition equipment to validate the model results. The synthetically generated schedules captured an average of 60 percent of household travel distance, and exhibited many of the characteristics of complex household travel, including day-to-day travel variation, and schedule coordination among household members. Future advances in the methodology may improve the model results, such as encouraging more detailed and accurate responses by providing a selection of generated schedules during the interview. Finally, the Constraints-based Transportation Resource Assignment Model (CTRAM) is introduced. Using an enumerative optimization approach, CTRAM determines the energy-minimizing vehicle-to-trip assignment decisions, considering trip schedules, occupancy, and vehicle capability. Designed to accept either actual or synthetic schedules, results of an application of the optimization model to the 2001 and 2009 National Household Travel Survey data show that U.S. households can reduce energy use by 10 percent, on average, by modifying the assignment of existing vehicles to trips. Households in 2009 show a higher tendency to assign vehicles optimally than in 2001, and multi-vehicle households with diverse fleets have greater savings potential, indicating that fleet modification strategies may be effective, particularly under higher energy price conditions.Ph.D.Natural Resources and EnvironmentUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91567/1/kevinb_1.pd

The impact of ‘Cash for Clunkers’ on greenhouse gas emissions: a life cycle perspective

One of the goals of the US Consumer Assistance to Recycle and Save (CARS) Act of 2009, more commonly known as 'Cash for Clunkers', was to improve the US vehicle fleet fuel efficiency. Previous studies of the program's environmental impact have focused mainly on the effect of improved fuel economy, and the resulting reductions in fuel use and emissions during the vehicle use phase. We propose and apply a method for analyzing the net effect of CARS on greenhouse gas emissions from a full vehicle life cycle perspective, including the impact of premature production and retirement of vehicles. We find that CARS had a one-time effect of preventing 4.4 million metric tons of CO2-equivalent emissions, about 0.4% of US annual light-duty vehicle emissions. Of these, 3.7 million metric tons are avoided during the period of the expected remaining life of the inefficient 'clunkers'. 1.5 million metric tons are avoided as consumers purchase vehicles that are more efficient than their next replacement vehicle would otherwise have been. An additional 0.8 million metric tons are emitted as a result of premature manufacturing and disposal of vehicles. These results are sensitive to the remaining lifetime of the 'clunkers' and to the fuel economy of new vehicles in the absence of CARS, suggesting important considerations for policymakers deliberating on the use of accelerated vehicle retirement programs as a part of the greenhouse gas emissions policy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85437/1/erl10_4_044003.pd

Guidelines for the Creation of a Program for Type III Environmental Declarations in the United States

Abstract There currently exists a demand in the United States for information about the environmental impacts of consumer products, but there is no consistent system for providing this information. This project proposes guidelines for the creation of a Type III environmental declaration program which will provide objective information about the environmental impacts of products based on life cycle assessment (LCA)methods. To more easily convey complicated information to consumers, the use of an original data presentation format, the “radar area graph”, was selected based on the results of a consumer survey. Because printed labels do not allow convenient product comparisons, a model internet website was created to demonstrate the potential of interactive product data. One original recommendation is an interactive personal database that allows consumers to track the impacts of their activities, thus making data more interesting and useful to consumers. Because evaluating products using LCA can be time consuming, we created a method of efficiently and consistently calculating environmental impacts. It includes guidelines for defining system boundaries and functional units, and for characterizing environmental impacts. Ten environmental impact category indicators were selected, and original methods were developed for characterizing land use and water depletion using spatial data. A spreadsheet calculator was created for determining human and ecological toxicity indicators. Finally, original software was developed to demonstrate the proposal for a common database of process and material parameters. To guide an administrator during the creation of a new Type III program, recommendations are provided for organizational structure, product registration procedures, and budget management for continued operation and growth.Master of ScienceNatural Resources and EnvironmentUniversity of Michigan, School of Natural Resources and Environmenthttp://deepblue.lib.umich.edu/bitstream/2027.42/35333/2/Guidelines for Type III Declarations - Full Report - by Bolo.pd

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Scientific and Regulatory Policy Committee Best Practices: Recommended ("Best") Practices for Informed (Non-blinded) Versus Masked (Blinded) Microscopic Evaluation in Animal Toxicity Studies.

This article describes the Society of Toxicologic Pathology's (STP) five recommended ("best") practices for appropriate use of informed (non-blinded) versus masked (blinded) microscopic evaluation in animal toxicity studies intended for regulatory review. (1) Informed microscopic evaluation is the default approach for animal toxicity studies. (2) Masked microscopic evaluation has merit for confirming preliminary diagnoses for target organs and/or defining thresholds ("no observed adverse effect level" and similar values) identified during an initial informed evaluation, addressing focused hypotheses, or satisfying guidance or requests from regulatory agencies. (3) If used as the approach for an animal toxicity study to investigate a specific research question, masking of the initial microscopic evaluation should be limited to withholding only information about the group (control or test article-treated) and dose equivalents. (4) The decision regarding whether or not to perform a masked microscopic evaluation is best made by a toxicologic pathologist with relevant experience. (5) Pathology peer review, performed to verify the microscopic diagnoses and interpretations by the study pathologist, should use an informed evaluation approach. The STP maintains that implementing these five best practices has and will continue to consistently deliver robust microscopic data with high sensitivity for animal toxicity studies intended for regulatory review. Consequently, when conducting animal toxicity studies, the advantages of informed microscopic evaluation for maximizing sensitivity outweigh the perceived advantages of minimizing bias through masked microscopic examination

An Isolated Limb Infusion Method Allows for Broad Distribution of rAAVrh74.MCK.GALGT2 to Leg Skeletal Muscles in the Rhesus Macaque

Recombinant adeno-associated virus (rAAV)rh74.MCK.GALGT2 is a muscle-specific gene therapy that is being developed to treat forms of muscular dystrophy. Here we report on an isolated limb infusion technique in a non-human primate model, where hindlimb blood flow is transiently isolated using balloon catheters to concentrate vector in targeted leg muscles. A bilateral dose of 2.5 × 1013 vector genomes (vg)/kg/limb was sufficient to induce GALGT2-induced glycosylation in 10%–60% of skeletal myofibers in all leg muscles examined. There was a 19-fold ± 6-fold average limb-wide increase in vector genomes per microgram genomic DNA at a bilateral dose of 2.5 × 1013 vg/kg/limb compared with a bilateral dose of 6 × 1012 vg/kg/limb. A unilateral dose of 6 × 1013 vg/kg/limb showed a 12- ± 3-fold increase in treated limb muscles compared to contralateral untreated limb muscles, which received vector only after release into the systemic circulation from the treated limb. Variability in AAV biodistribution between different segments of the same muscle was 125% ± 18% for any given dose, while variability between the same muscle for any given treatment dose was 45% ± 7%. These experiments demonstrate that treatment of muscles throughout the leg with rAAVrh74.MCK.GALGT2 can be accomplished safely using an isolated limb infusion technique, where balloon catheters transiently isolate the limb vasculature, but that intra- and inter-muscle transduction variability is a significant issue. Keywords: limb perfusion, gene therapy, Galgt2, muscular dystroph

Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database

Background: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p &lt; 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p &lt; 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Extending chemical perturbations of the ubiquitin fitness landscape in a classroom setting reveals new constraints on sequence tolerance

Although the primary protein sequence of ubiquitin (Ub) is extremely stable over evolutionary time, it is highly tolerant to mutation during selection experiments performed in the laboratory. We have proposed that this discrepancy results from the difference between fitness under laboratory culture conditions and the selective pressures in changing environments over evolutionary timescales. Building on our previous work (Mavor et al., 2016), we used deep mutational scanning to determine how twelve new chemicals (3-Amino-1,2,4-triazole, 5-fluorocytosine, Amphotericin B, CaCl2, Cerulenin, Cobalt Acetate, Menadione, Nickel Chloride, p-Fluorophenylalanine, Rapamycin, Tamoxifen, and Tunicamycin) reveal novel mutational sensitivities of ubiquitin residues. Collectively, our experiments have identified eight new sensitizing conditions for Lys63 and uncovered a sensitizing condition for every position in Ub except Ser57 and Gln62. By determining the ubiquitin fitness landscape under different chemical constraints, our work helps to resolve the inconsistencies between deep mutational scanning experiments and sequence conservation over evolutionary timescales

Extending chemical perturbations of the ubiquitin fitness landscape in a classroom setting reveals new constraints on sequence tolerance.

Although the primary protein sequence of ubiquitin (Ub) is extremely stable over evolutionary time, it is highly tolerant to mutation during selection experiments performed in the laboratory. We have proposed that this discrepancy results from the difference between fitness under laboratory culture conditions and the selective pressures in changing environments over evolutionary timescales. Building on our previous work (Mavor et al., 2016), we used deep mutational scanning to determine how twelve new chemicals (3-Amino-1,2,4-triazole, 5-fluorocytosine, Amphotericin B, CaCl2, Cerulenin, Cobalt Acetate, Menadione, Nickel Chloride, p-Fluorophenylalanine, Rapamycin, Tamoxifen, and Tunicamycin) reveal novel mutational sensitivities of ubiquitin residues. Collectively, our experiments have identified eight new sensitizing conditions for Lys63 and uncovered a sensitizing condition for every position in Ub except Ser57 and Gln62. By determining the ubiquitin fitness landscape under different chemical constraints, our work helps to resolve the inconsistencies between deep mutational scanning experiments and sequence conservation over evolutionary timescales