Differentiating and Mitigating Methane Emissions from Fugitive Leaks from Natural Gas Distribution, Historic Landfills, and Manholes in Montréal, Canada.

Rapidly reducing urban methane (CH4) emissions is a critical component of strategies aimed at limiting climate change. Individual source measurements provide the details necessary to develop actionable mitigation strategies and are highly complementary to mobile surveys and other top-down methods. Here, we perform 615 individual source measurements in Montréal, Canada, to quantify CH4 emissions from historic landfills, manholes, and fugitive emissions from natural gas (NG) distribution systems. We find that in 2020, historic landfills produced 901 (452 to 1541, 95% c.i.) tons of CH4, manholes emitted 786 (32 to 2602, 95% c.i.) tons of CH4, and NG distribution systems emitted 451 (176-843, 95% c.i.) tons of CH4, placing them all within the top four CH4 sources in Montréal. Methane emissions from both historic landfills and manholes are not accounted for in any greenhouse gas inventory. We find that geochemistry alone cannot positively identify source subcategories (e.g., type of manhole or NG infrastructure) in almost all cases, although C2/C1 ratios can distinguish NG distribution sources from biogenic sources (historic landfills and manholes). Using our individual source measurement data, we show that historic landfills have the greatest potential for CH4 reductions but the highest mitigation costs, unless we target the highest emitting landfills. In contrast, CH4 emissions from manholes can be reduced at low costs, but reduction methods are commercially unavailable. For NG distribution, methods such as increasing repair rates for high-emitting industrial meters can greatly reduce mitigation costs and emissions. Overall, our results highlight the role of individual source measurements in developing actionable CH4 mitigation strategies to meet municipal, regional, and national climate action plans.

Methane Emissions from Abandoned Oil and Gas Wells in Canada and the United States.

Abandoned oil and gas wells are one of the most uncertain sources of methane emissions into the atmosphere. To reduce these uncertainties and improve emission estimates, we geospatially and statistically analyze 598 direct methane emission measurements from abandoned oil and gas wells and aggregate well counts from regional databases for the United States (U.S.) and Canada. We estimate the number of abandoned wells to be at least 4,000,000 wells for the U.S. and at least 370,000 for Canada. Methane emission factors range from 1.8 × 10-3 g/h to 48 g/h per well depending on the plugging status, well type, and region, with the overall average at 6.0 g/h. We find that annual methane emissions from abandoned wells are underestimated by 150% in Canada and by 20% in the U.S. Even with the inclusion of two to three times more measurement data than used in current inventory estimates, we find that abandoned wells remain the most uncertain methane source in the U.S. and become the most uncertain source in Canada. Understanding methane emissions from abandoned oil and gas wells can provide critical insights into broader environmental impacts of abandoned wells, which are rapidly growing in number around the world.

Occurrence and origin of groundwater methane in the Stellarton Basin, Nova Scotia, Canada.

Groundwater methane (CH4) in areas of fossil fuel development has been a recent focus of study as high CH4 concentrations pose water quality concerns and potential explosive hazards. In 2013, a provincial study in Nova Scotia identified areas with elevated groundwater CH4. However, due to limited data, the specific sources and local distribution of CH4 in those areas remain unknown. In this study, we examined the Stellarton Basin in central Nova Scotia, Canada, a region with an abundance of coal formations, numerous abandoned coal mines, and an active open pit coal mine. Methane was detected in 94% of water samples that were sampled from 45 private water wells. Six water wells exceeded the 28 mg/L hazard mitigation threshold with CH4 levels of up to 72.7 mg/L. The δ13CCH4 (-85.5 to -48.5‰) and the δ2HCH4 (-280 to -88‰) indicated that >95% of samples had CH4 of microbial origin. However, the detection of ethane (C2H6) up to 2.97 mg/L and propane (C3H8) up to 0.008 mg/L, as well as the δ13CC2H6 values (-30.1 to -15.6‰) suggested a mixture of microbial CH4 with trace thermogenic gas, likely migrated from Stellarton coals (δ13CC2H6 of -27.6 to -15.35‰). A mobile greenhouse gas analyzer survey was conducted within the perimeter of residences and off-gassing from taps had atmospheric CH4 measurements as high as 66 ppmv. This study integrates multiple sampling and monitoring methods to investigate groundwater CH4 in a coal-bearing region. The findings advance the understanding of the origin and occurrence of CH4 in complex groundwater systems. The data acquired in this study may be used as a pre-drill baseline for groundwater CH4 concentrations and origins should coal-bed methane operations in Nova Scotia proceed in the future.

Microbial lag phase can be indicative of, or independent from, cellular stress.

Measures of microbial growth, used as indicators of cellular stress, are sometimes quantified at a single time-point. In reality, these measurements are compound representations of length of lag, exponential growth-rate, and other factors. Here, we investigate whether length of lag phase can act as a proxy for stress, using  a number of model systems (Aspergillus penicillioides; Bacillus subtilis; Escherichia coli; Eurotium amstelodami, E. echinulatum, E. halophilicum, and E. repens; Mrakia frigida; Saccharomyces cerevisiae; Xerochrysium xerophilum; Xeromyces bisporus) exposed to mechanistically distinct types of cellular stress including low water activity, other solute-induced stresses, and dehydration-rehydration cycles. Lag phase was neither proportional to germination rate for X. bisporus (FRR3443) in glycerol-supplemented media (r2 = 0.012), nor to exponential growth-rates for other microbes. In some cases, growth-rates varied greatly with stressor concentration even when lag remained constant. By contrast, there were strong correlations for B. subtilis in media supplemented with polyethylene-glycol 6000 or 600 (r2 = 0.925 and 0.961), and for other microbial species. We also  analysed data from independent studies of food-spoilage fungi under glycerol stress (Aspergillus aculeatinus and A. sclerotiicarbonarius); mesophilic/psychrotolerant bacteria under diverse, solute-induced stresses (Brochothrix thermosphacta, Enterococcus faecalis, Pseudomonas fluorescens, Salmonella typhimurium, Staphylococcus aureus); and fungal enzymes under acid-stress (Terfezia claveryi lipoxygenase and Agaricus bisporus tyrosinase). These datasets also exhibited diversity, with some strong- and moderate correlations between length of lag and exponential growth-rates; and sometimes none. In conclusion, lag phase is not  a reliable measure of stress because length of lag and growth-rate inhibition are sometimes highly correlated, and sometimes not at all.

Methane emissions from abandoned coal and oil and gas developments in New Brunswick and Nova Scotia.

Energy reserves have been exploited in the Atlantic Canadian provinces since the early 1600s, and many fossil fuel extraction sites have been abandoned over this long history of energy development. Oil, natural gas, and coal extraction sites are a source of greenhouse gas emissions, particularly for methane (CH4). In this study, we used multiple sampling methods to measure CH4 from abandoned coal mine openings in Nova Scotia and a legacy oilfield in New Brunswick. Atmospheric and shallow soil gases were sampled around legacy sites using flux rate chamber measurements (spatial and temporal) and plot-scale atmospheric gas surveys, in addition to regional gas screening surveys over larger populations of sites to confirm whether small-scale observations were reflected regionally. Only one oil and gas site (2.4 ± 3.1⋅ 102 mg m- 2 day- 1) and one abandoned coal mine opening (1.0 ± 1.1⋅ 102 mg m- 2 day- 1) were affected by soil CH4 migration, though rates of leakage were minimal and would rank as low severity on industrial scales. Plot-scale atmospheric gas screening showed super-ambient CH4 concentrations at 5 sites in total (n = 16), 2 coal adits and 3 abandoned oil and gas wells. Regional gas screening surveys suggest that 11% of legacy oil and gas sites have some emission impacts, compared with 1-2% of legacy coal sites. These frequencies are close, albeit lower than the 15% of legacy oil and gas sites and 10% of abandoned coal mine openings flagged from our aggregated small-scale observations. These sites may emit less than other developments studied to date either because more time has elapsed since extraction, or because differences in regional geology reduce the likelihood of sustained emissions. This study provides valuable information to help understand the methane emission risks associated with legacy energy sites.

Introducing a new sedation policy in a large district general hospital: before and after cohort analysis.

BACKGROUND: The management of pain, agitation and sedation for ventilated patients who are admitted to intensive care is an essential part of their care. The introduction of sedation protocols is associated with improved patient outcomes. METHODS: We conducted an observational cohort study among mechanically ventilated patients in a 16-bed ICU over a two-year period. We retrospectively examined data from two patient populations, namely those before and after the introduction of a new sedation protocol in July 2015. The primary outcome was the duration of mechanical ventilation in both groups. RESULTS: After the implementation of the new sedation protocol, there was a significant decrease in the mean duration of mechanical ventilation (1.45 days). Furthermore, we observed a non-significant reduction in the mean duration of ICU stay. CONCLUSION: The new protocol was associated with outcome improvements including: decreased mean duration of mechanical ventilation and a reduced number of ventilated days; and increased patient throughput with a slight increase in the length of vasopressor support. Moreover, the use of a structure-process-outcome model of quality improvement was associated with significant improvements in process measures of quality.

Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection.

OBJECTIVE(S): An HIV cure will impose aviraemia that is sustained following the withdrawal of antiretroviral therapy (ART). Understanding the efficacy of novel interventions aimed at curing HIV requires characterization of both natural viral control and the effect of ART on viral control after treatment interruption. DESIGN: Analysis of transient viral control in recent seroconverters in the Short Pulse AntiRetroviral Therapy at Acute Seroconversion trial. METHODS: We compared untreated and treated HIV seroconverters (n = 292) and identified periods of control (plasma HIV RNA < 400 copies/ml for ≥16 weeks off therapy) in 7.9% of ART-naive participants, and in 12.0% overall. HIV DNA was measured by qPCR, and HIV-specific CD8 responses were measured by enzyme-linked immunosorbent spot assay (ELISpot). T-cell activation and exhaustion were measured by flow cytometry. RESULTS: At baseline, future controllers had lower HIV DNA, lower plasma HIV RNA, higher CD4 : CD8 ratios (all P < 0.001) and higher CD4 cell counts (P < 0.05) than noncontrollers. Among controllers, the only difference between the untreated and those who received ART was higher baseline HIV RNA in the latter (P = 0.003), supporting an added ART effect. CONCLUSION: Consideration of spontaneous remission in untreated individuals will be critical to avoid overestimating the effect size of new interventions used in HIV cure studies.

Development and implementation of a theatre booking form and morning briefing meeting to improve emergency theatre efficiency.

The aim of this study was to improve emergency theatre efficiency via the introduction of a theatre booking form and morning briefing meeting. Process mapping was used to engage staff and consider if the emergency theatre may benefit from the application of a structured process of communication. A theatre booking form and morning briefing meeting were implemented to promote change. Efficiency was measured by theatre utilisation and characterised into neutral time, efficient time and inefficient time. The results demonstrated a 12.9% increase in efficient time, 3.3% fall in inefficient time and 9.6% fall in neutral time post-implementation, during the high volume work period of 08:00 to 17:59 on weekdays. No improvement in efficiency was demonstrated outside these hours or on weekends during lower volume workloads. Utilisation of a theatre booking form and morning briefing meeting improved emergency theatre efficiency during high volume work periods by the application of a structured process of communication.

Immunological biomarkers predict HIV-1 viral rebound after treatment interruption.

Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of 'post-treatment control' (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication.

HIV-1 DNA predicts disease progression and post-treatment virological control.

In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.

High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse.

Macrophage infection is considered to play an important role in HIV-1 pathogenesis and persistence. Using a primary cell-based coculture model, we show that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity HIV-1 infection to autologous CD4(+) T cells through a viral envelope glycoprotein (Env) receptor- and actin-dependent virological synapse (VS), facilitated by interactions between ICAM-1 and LFA-1. Virological synapse (VS)-mediated transmission by MDM results in high levels of T cell HIV-1 integration and is 1 to 2 orders of magnitude more efficient than cell-free infection. This mode of cell-to-cell transmission is broadly susceptible to the activity of CD4 binding site (CD4bs) and glycan or glycopeptide epitope-specific broadly neutralizing monoclonal antibodies (bNMAbs) but shows resistance to bNMAbs targeting the Env gp41 subunit membrane-proximal external region (MPER). These data define for the first time the structure and function of the macrophage-to-T cell VS and have important implications for bNMAb activity in HIV-1 prophylaxis and therapy. IMPORTANCE The ability of HIV-1 to move directly between contacting immune cells allows efficient viral dissemination with the potential to evade antibody attack. Here, we show that HIV-1 spreads from infected macrophages to T cells via a structure called a virological synapse that maintains extended contact between the two cell types, allowing transfer of multiple infectious events to the T cell. This process allows the virus to avoid neutralization by a class of antibody targeting the gp41 subunit of the envelope glycoproteins. These results have implications for viral spread in vivo and the specificities of neutralizing antibody elicited by antibody-based vaccines.

Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity.

The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells.

Liposome-mediated delivery of iminosugars enhances efficacy against dengue virus in vivo.

A key challenge faced by promising antiviral drugs, such as iminosugars, is in vivo delivery to achieve effective levels of drug without toxicity. Four iminosugars, all deoxynojirimycin (DNJ) derivatives-N-butyl DNJ (NB-DNJ), N-nonyl DNJ, N-(9-methoxynonyl) DNJ, and N-(6'-[4″-azido-2″-nitrophenylamino]hexyl)-1-DNJ (NAP-DNJ)-potently inhibited both the percentage of cells infected with dengue virus and release of infectious virus from primary human monocyte-derived macrophages, demonstrating their efficacy in primary cells. In a lethal antibody-dependent enhancement mouse model of dengue pathogenesis, free NB-DNJ significantly enhanced survival and lowered viral load in organs and serum. Liposome-mediated delivery of NB-DNJ, in comparison with free NB-DNJ, resulted in a 3-log(10) reduction in the dose of drug sufficient to enhance animal survival. The optimizing of the effective dose in this way could liberate the therapeutic potential of many cytotoxic antivirals against both dengue virus and a wide array of other viruses.

Treatment of type II endoleaks associated with left subclavian artery coverage during thoracic aortic stent grafting.

OBJECTIVE: Increasing experience with thoracic aortic stent grafts has led to a more aggressive approach to thoracic aortic pathologies in the distal aortic arch and proximal descending thoracic aorta. To increase the length of the proximal landing zone, it is sometimes necessary to cover the left subclavian artery with the thoracic stent-graft, introducing the risk of retrograde filling of the excluded aorta from the left subclavian artery. It is currently unclear how best to manage these patients to prevent persistent risk of aneurysm expansion or rupture. We report our experience with a minimally invasive endovascular repair of the covered left subclavian artery. METHODS: We reviewed prospectively gathered data on all investigational device exemption-approved patients undergoing thoracic aortic stent grafting at the Arizona Heart Institute from 2000 to 2006 (n = 289 patients). Patients had surveillance with a contrast-enhanced computed tomography scan on the first postoperative day and during follow-up at 1, 6, and 12 months. RESULTS: A total of 289 patients received thoracic stent grafts during the study: Medtronic Talent (Medtronic, Minneapolis, Minn) (n = 25) or Gore TAG (WL Gore & Associates Inc, Flagstaff, Ariz) (n = 261). The left subclavian artery was covered in 23% of patients (n = 66), of whom 17% had preoperative carotid-subclavian bypass (n = 11/66). Among patients with left subclavian artery coverage, the 30-day mortality was 6.1% (n = 4), procedure-related strokes developed in 3 patients (n = 3, 4.6%), and the incidence of left arm claudication was 7.6% (n = 5), necessitating postoperative carotid-subclavian bypass in 2 patients. Twelve patients (18%) had a type I (n = 6) or II (n = 7) endoleak. Coverage of the left subclavian artery accounted for 71% of the type II endoleaks (n = 5), whereas patent intercostals accounted for the rest (n = 2). Type II endoleaks associated with left subclavian artery coverage were successfully treated by retrograde coil embolization from the left brachial artery (n = 3) or left subclavian artery ligation (n = 1). CONCLUSION: Coverage of the left subclavian artery during thoracic aortic stent grafting is associated with a low incidence of arm complications and type II endoleaks. All type II endoleaks were successfully treated by retrograde coil embolization or ligation of the left subclavian artery. Successful treatment of endoleaks may reduce the risk of aneurysm expansion or rupture.

A novel approach for the endovascular repair of the small thoracic aorta: customizing off-the-shelf endoluminal grafts to treat a post-coarctation pseudoaneurysm.

Surgical repair of post-coarctation pseudoaneurysm is associated with high morbidity and mortality. Endovascular stent grafting is a minimally invasive approach to manage this condition. The small thoracic aorta provides a dilemma for endovascular stent grafting using available commercially available thoracic endografts. We describe a hybrid approach including a novel technique to customize various components of the abdominal endoluminal grafts to repair a post-coarctation pseudoaneurysm. The patient is doing well at 1-year follow-up with no endoleaks.

Endovascular management of a descending thoracic mycotic aneurysm: mid-term follow-up.

Open surgical repair of mycotic aneurysm is associated with a high surgical morbidity and mortality. Endovascualr graft management of thoracic aortic aneurysm has been associated with a less surgical risk. The role of endovascular graft repair of mycotic aneurysm remains controversial since graft material remains in contact with possible infected tissue. We report the marked thrombosis and marked regression of a thoracic mycotic aneurysm with an endovascular graft at mid-term follow-up.