Effects of apoB-derived peptide vaccination in a murine model of systemic lupus erythematosus

OBJECTIVE: Atherosclerotic disease progression is mediated in part, by immunological mechanisms. In recent years, interest has increased towards the prospect of modulating these immune mechanisms through vaccination to ameliorate the course of disease. Patients with lupus are at a significantly higher risk for accelerated atherosclerosis and related complications. The goal of this study was to assess the outcome of immunization in mouse models of lupus, and lupus with accelerated atherosclerosis. MATERIALS/METHODS: Atherosclerosis-prone apoE^-/- mice and autoimmune gld mice were previously crossed to generate the gld.apoE^-/- mouse. Mice were treated with an apoB-100-derived vaccine, Alum (adjuvant control), or PBS control. The antibody response was determined by quantifying the amount of circulating anti-apoB100. Serum triglyceride and cholesterol levels were analyzed. Kidney tissue from gld and gld.apoE^-/- mice was processed and histologically analyzed, using glomerular tuft size as a measure of renal disease and by extension, autoimmune disease severity. Results: Immunization led to a pronounced initial antibody response that was decreased by the endpoint of the study. No significant differences in serum triglyceride or cholesterol were observed regardless of treatment. Similarly, no significant differences were observed in glomerular tuft size. Conclusion: The data suggests that immunization with an apoB-100- derived vaccine neither improves nor worsens autoimmune disease severity in the gld.apoE^-/- mouse model. It also appears that immunization is tolerated in the autoimmune background. While further study is necessary to determine the efficacy of immunization in reducing atherosclerotic disease in this model, this may be a possible therapy to lower incidence of atherosclerosis in lupus patients

Emerging Multidrug Resistance of Methicillin-Resistant Staphylococcus aureus in Hand Infections.

BACKGROUND: Methicillin-resistant Staphylococcus aureus has been the most commonly identified pathogen in hand infections at urban centers, but the evolving antibiotic sensitivity profiles of methicillin-resistant Staphylococcus aureus are not known. The purposes of this study are to determine if multidrug resistance in methicillin-resistant Staphylococcus aureus is emerging and to provide current recommendations for empiric antibiotic selection for hand infections in endemic regions. METHODS: An eight-year longitudinal, retrospective chart review was performed on all culture-positive hand infections encountered by an urban hospital from 2005 to 2012. The proportions of all major organisms were calculated for each year. Methicillin-resistant Staphylococcus aureus infections were additionally analyzed for antibiotic sensitivity. RESULTS: A total of 683 culture-positive hand infections were identified. Overall, methicillin-resistant Staphylococcus aureus grew on culture in 49% of cases; the annual incidence peaked at 65% in 2007. Over the study period, methicillin-resistant Staphylococcus aureus was universally resistant to penicillin, oxacillin, and ampicillin. Clindamycin resistance significantly increased, approaching 20% by 2012 (p = 0.02). Levofloxacin resistance linearly increased from 12% to 50% (p \u3c 0.01). Resistance to trimethoprim-sulfamethoxazole, tetracycline, gentamicin, and moxifloxacin was only sporadically observed. Resistance to vancomycin, daptomycin, linezolid, and rifampin was not observed. CONCLUSIONS: Significant increases in resistance to clindamycin and levofloxacin were observed in recent years, and empiric therapy with these drugs may have limited efficacy, especially in urban centers. CLINICAL RELEVANCE: Hand infections caused by methicillin-resistant Staphylococcus aureus may be developing increasing resistance to clindamycin and levofloxacin in recent years. This longitudinal study examines the effectiveness of a variety of antibiotics to methicillin-resistant Staphylococcus aureus

Life Cycle Assessment of Environmental and Economic Impacts of Deploying Alternative Urban Bus Powertrain Technologies in the South Coast Air Basin [Research Brief]

To address issues of air quality and greenhouse gas emissions in the South Coast Air Basin, local transit agencies are considering shifting their urban buses to battery electric buses (BEBs) and hydrogen fuel cell electric buses (FCEBs). However, each of these options vary in their effectiveness in reducing emissions over their life cycle, associated life cycle costs and environmental footprint, and ability to meet operational needs

Nationwide, population-based observational study of the molecular epidemiology and temporal trend of carbapenemase-producing Enterobacterales in Norway, 2015 to 2021

National and regional carbapenemaseproducing Enterobacterales (CPE) surveillance is essential to understand the burden of antimicrobial resistance, elucidate outbreaks, and develop infection-control or antimicrobial-treatment recommendations. Aim: This study aimed to describe CPE and their epidemiology in Norway from 2015 to 2021. Methods: A nationwide, population-based observational study of all verified clinical and carriage CPE isolates submitted to the national reference laboratory was conducted. Isolates were characterised by antimicrobial susceptibility testing, whole genome sequencing (WGS) and basic metadata. Annual CPE incidences were also estimated. Results: A total of 389 CPE isolates were identified from 332 patients of 63years median age (range:0–98). These corresponded to 341 cases, 184 (54%) being male. Between 2015 and 2021, the annual incidence of CPE cases increased from 0.6 to 1.1per 100,000person-years. For CPEisolates with available data on colonisation/infection, 58% (226/389)were associated with colonisation and 38% (149/389) with clinical infections. WGS revealed a predominance of OXA-48-like (51%; 198/389) and NDM (34%; 134/389) carbapenemases in a diversified population of Escherichia coli and Klebsiella pneumoniae, including high-risk clones also detected globally. Most CPE isolates were travel-related (63%;245/389). Although local outbreaks and healthcare-associated transmission occurred, no interregional spread was detected. Nevertheless, 18% (70/389) of isolates not directly related to import points towards potentially unidentified transmission routes. A decline in travelassociated cases was observed during the COVID-19 pandemic. Conclusions: The close-to-doubling of CPE case incidence between 2015 and 2021 was associated with foreign travel and genomic diversity. To limit further transmission and outbreaks, continued screening and monitoring is essential

Cost-Benefit Analysis of Additional Energy Storage Procurement

California has ambitious goals for reducing and eliminating greenhouse gas emissions from the State’s electricity system as a cornerstone of efforts to decarbonize the State’s economy more broadly. Electricity decarbonization efforts are codified by Senate Bill (SB) 100 which seeks to have 100% of retail sales of electricity by the year 2045 provided by eligible zero-carbon resources with an interim target of 60% of retail sales of electricity provided by eligible renewable resources by the year 2030. This policy contributes to a broader goal of achieving economy-wide carbon neutrality in the State by 2045, codified by Executive Order B-55-18.Planning studies were undertaken to determine how California should proceed in terms of electricity generation and storage resource rollout to meet these goals, such as the Senate Bill 100 Joint Agency Report [1], which highlights the need for rapid renewable resource and energy storage buildout. Energy storage is typically selected as utility-scale lithium-ion batteries for short-duration storage and pumped hydropower energy storage for long-duration energy storage functions, primarily due to their relatively low cost for the former and technological maturity for the latter. Since the capacity expansion models used for such planning studies focus on minimizing cost, the recommended course from these studies focuses on lithium-ion and pumped hydropower energy storage connected as utility energy storage.In practice, however, energy storage deployment will not be dictated by a central plan. Energy storage is being deployed to serve different priorities. Behind-the-meter energy storage may be deployed by individual residential, commercial, and industrial customers to serve their specific needs, provide electricity savings, and enable higher uptake of local renewable resources. Energy storage may also be installed at wind or solar farms to enable these to act as more dispatchable resources for the electric grid and enable them to provide electricity to the grid when they would otherwise not be generating. Additionally, other energy storage technologies such as flow batteries and hydrogen energy storage are emerging as potential alternatives to lithium-ion batteries and pumped hydropower, each with its own advantages and disadvantages in terms of technical, economic, and practical (i.e. safety, recyclability, etc...) characteristics.Energy storage is a critical enabler of plans for complying with Senate Bill 100 and broader economy-wide decarbonization goals. Therefore, it is critical to understand the effect of alternative configurations for energy storage deployment on the broader electricity system’s ability to rely on zero-carbon electricity for meeting load, how well it can use available renewable electricity generation, and the system-wide cost of electricity.Therefore, the goal of this project is to provide information on the preferred configuration of energy storage technologies for supporting a decarbonized California electric grid by investigating alternative configurations for the buildout of energy storage to meet California’s electricity decarbonization goals and comparing them to the configuration suggested by Senate Bill 100 planning studies

Life Cycle Assessment of Environmental and Economic Impacts of Deploying Alternative Urban Bus Powertrain Technologies in the South Coast Air Basin

To aid in addressing issues of air quality and greenhouse gas (GHG) emissions in the South Coast Air Basin, local transit agencies are considering a shift to battery electric buses (BEBs) and hydrogen fuel cell electric buses (FCEBs). Each of these options vary in their overall effectiveness in reducing different emission types over their life cycle, associated life cycle costs, ability to meet operational needs of transit agencies, and life cycle environmental footprint. This project carried out a life cycle-based analysis and comparison of the GHG emissions, criteria pollutant emissions, and other environmental externalities associated with BEBs and FCEBs, taking into account their ability to meet operational constraints of the Orange County Transportation Authority. From an environmental footprint perspective, this study found the following. First, both FCEBs and long-range BEBs have comparable impacts for global warming potential and particulate matter formation but when the FCEBs were fueled using renewable hydrogen. Second, using electricity from the current California grid mix to drive electrolysis to produce hydrogen for FCEBs produced only marginal benefits compared to current natural-gas fueled vehicles due to the low supply chain efficiency of this pathway. Third, the mining of precious metals is a major contributor to environmental footprint categories for both BEBs and FCEBs. Fourth, both FCEVs and long-range BEBs provide significant reductions in environmental footprint compared to conventional diesel and natural gas buses. From a cost perspective, this study found the following. First, with current-day cost inputs, FCEBs and BEBs have comparable total cost of ownership, but both have slightly higher costs than diesel and natural gas buses. Second, FCEBs have an equivalent total cost of ownership to BEBs when the electricity rate for charging is $0.24/kWh. Higher values render FCEBs as the cheaper option and lower values render BEBs as the cheaper option. Second, the total cost of ownership of these technologies is highly sensitive to electricity costs, and the rapid evolution of the electricity system has strong implications for the economic comparison between BEBs and FCEBs. Overall, this study finds that while both FCEBs and BEBs provide life-cycle environmental benefits, further cost reductions in electricity rates and initial purchase costs are needed to achieve total cost of ownership parity with conventional bus powertrains. With the rapid evolution of the electricity system and falling costs for renewable electricity resources, these cost reductions may occur in the near future

Evaluating options for balancing the water-electricity nexus in California: Part 2--greenhouse gas and renewable energy utilization impacts.

A study was conducted to compare the technical potential and effectiveness of different water supply options for securing water availability in a large-scale, interconnected water supply system under historical and climate-change augmented inflow and demand conditions. Part 2 of the study focused on determining the greenhouse gas and renewable energy utilization impacts of different pathways to stabilize major surface reservoir levels. Using a detailed electric grid model and taking into account impacts on the operation of the water supply infrastructure, the greenhouse gas emissions and effect on overall grid renewable penetration level was calculated for each water supply option portfolio that successfully secured water availability from Part 1. The effects on the energy signature of water supply infrastructure were found to be just as important as that of the fundamental processes for each option. Under historical (baseline) conditions, many option portfolios were capable of securing surface reservoir levels with a net neutral or negative effect on emissions and a benefit for renewable energy utilization. Under climate change augmented conditions, however, careful selection of the water supply option portfolio was required to prevent imposing major emissions increases for the system. Overall, this analysis provided quantitative insight into the tradeoffs associated with choosing different pathways for securing California's water supply