Spatiotemporal investigation of geochemical and hydrological controls on release of soluble reactive phosphorus from the shallow aquifer of a riparian zone.

Phosphorus (P) that accumulates in agricultural riparian zones can be released under certain hydrological and biogeochemical conditions, thereby limiting the effectiveness of these zones in reducing P loads from field to stream. The study objective was to explore factors that may be contributing to, or limiting, high soluble reactive phosphorus (SRP) concentrations in the shallow aquifer of an alluvial upland riparian zone located in a continental climate. Field investigations including porewater sampling from six vertical nests, soil sampling, and continuous soil moisture, groundwater table, and redox measurements were conducted over 19 months. Porewater SRP concentrations were generally low in the aquifer considering all sampling times (median = 14.7 µg/L; interquartile range [IQR] = 11.1 µg/L, 287 samples). The overall low SRP may be due to low reducible labile soil P (median = 21.1 µgP/g dw, IQR = 10.9 µgP/g dw, 21 samples). However, high SRP concentrations (>52 µg/L, 95% quartile) did occur intermittently in space and time with no clear spatial or temporal patterns. Analyses indicate that most high concentrations were likely not associated with factors previously reported to influence SRP release in riparian aquifers, including redox conditions, pH, and soil drying and wetting. Further, data indicate that internally released or externally supplied SRP may undergo rapid (re-) sequestration within the aquifer, limiting its vertical or horizontal transport. The study findings highlight the complexity of P behavior in riparian zones and the need for caution when assessing the effectiveness of conservation practices and in interpreting potential impacts of subsurface water quality on stream water quality when monitoring locations are distant from the stream.

Characterization of subsurface pathways contributing to freshwater salinization of urban streams using electrical and electromagnetic imaging techniques.

Salinization of inland fresh surface waters in temperate climates is a growing concern due to increasing salt inputs from sources including chloride (Cl)-containing road salt de-icers, industrial waste, and landfill leachate. Groundwater pathways play an important role in the year-round delivery of Cl to streams, but quantifying this pathway, including spatiotemporal variability and amount of Cl mass stored in the subsurface, is challenging. The objective of this study was to demonstrate, evaluate, and compare the potential applications of the geoelectrical techniques - electromagnetics (EM) and direct current (DC) resistivity - for mapping salt contamination in shallow urban groundwater and characterizing the groundwater pathways delivering Cl to urban streams. EM and DC surveys were conducted (3D mapping and 2D time-lapse) across a 20 m salt-impacted stream section and surrounding riparian zone that is located near an arterial road and parking lot. Groundwater samples and soil cores were also collected to validate the geoelectrical results. Both the EM and DC surveys detected high salt concentrations in the shallow subsurface (up to 3 m depth) near the road, parking lot, and stream; however, DC more accurately represented groundwater Cl concentrations. DC results were used to calculate the total Cl mass in the subsurface, with the spatial mass distribution used to infer the temporal variability in the subsurface salt plume. Finally, time-lapse DC showed that the highest groundwater salt concentrations existed near the stream between June and October - this is expected to contribute to the elevated salt concentrations in the stream during summer months. This study has shown that EM and DC can be useful for identifying groundwater salt concentration, storage, and transport in a non-intrusive and efficient manner, making them valuable field tools for characterizing and quantifying groundwater salt pathways to urban streams.

Multizone Aquatic Ecological Exposures to Landfill Contaminants from a Groundwater Plume Discharging to a Pond.

While it is recognized that groundwater contaminant plumes can impact surface waters, there remains little information on the magnitude, spatial extent, and especially temporal variability of the resulting exposure to the variety of aquatic organisms, particularly for stagnant surface waters (e.g., ponds). The present study of a historic landfill plume discharging to a pond investigated contaminant exposure to multiple aquatic zones (endobenthic, epibenthic, pelagic) over approximately 1 year within a temperate climate. Landfill tracers included the artificial sweetener saccharin, ammonium, chloride, and specific conductance. Sampling of pond sediment porewater (upwelling groundwater) and continuous geophysical imaging of the subsurface showed a relatively stable plume footprint covering approximately 26% of the pond, although with spatially varying leachate composition, revealing year-round exposure to endobenthic (within sediments) organisms. Substantial and variable contaminant exposure to epibenthic organisms within the plume footprint was shown by elevated specific conductance measured directly above the sediment interface. Exposure varied daily at times and increased through winter to values representing undiluted plume groundwater. Exposure to pelagic organisms (overlying water) covered a larger area (~50%) due to in-pond circulation. The stream outlet concentrations were stable at approximately 10 times dilution for chloride and saccharin, but were substantially less in summer for ammonium due to in-pond processes. Whereas groundwater contaminants are typically assumed elevated at base flows, the outlet stream contaminant mass discharges to downstream receptors were notably higher in winter than summer, following stream flow patterns. Insights from the present study into the timings and locations of contaminant plume exposure to multiple ecological zones of a pond can provide guidance to contaminated site and aquatic ecosystem managers on improved monitoring, assessment, and remediation protocols. Environ Toxicol Chem 2023;42:1667-1684. © 2023 His Majesty the King in Right of Canada and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada.

The acute toxicity of bitumen-influenced groundwaters from the oil sands region to aquatic organisms.

The extraction of surface mined bitumen from oil sands deposits in northern Alberta, Canada produces large quantities of liquid tailings waste, termed oil sands process-affected water (OSPW), which are stored in large tailings ponds. OSPW-derived chemicals from several tailings ponds migrating past containment structures and through groundwater systems pose a concern for surface water contamination. The present study investigated the toxicity of groundwater from near-field sites adjacent to a tailings pond with OPSW influence and far-field sites with only natural oil sands bitumen influence. The acute toxicity of unfractionated groundwater and isolated organic fractions was assessed using a suite of aquatic organisms (Pimephales promelas, Oryzias latipes, Daphnia magna, Hyalella azteca, Lampsilis spp., Ceriodaphnia dubia, Hexagenia spp., and Vibrio fischeri). Assessment of unfractionated groundwater demonstrated toxicity towards all invertebrates in at least one far-field sample, with both near-field and far-field samples with bitumen influence toxic towards P. promelas, while no toxicity was observed for O. latipes. When assessing the unfractionated groundwater and isolated organic fractions from near-field and far-field groundwater sites, P. promelas and H. azteca were the most sensitive to organic components, while D. magna and L. cardium were most sensitive to the inorganic components. Groundwater containing appreciable amounts of dissolved organics exhibited similar toxicities to sensitive species regardless of an OSPW or natural bitumen source. The lack of a clear distinction in relative acute toxicities between near-field and far-field samples indicates that the water-soluble chemicals associated with bitumen are acutely toxic to several aquatic organisms. This result, combined with the similarities in chemical profiles between bitumen-influenced groundwater originating from OSPW and/or natural sources, suggests that the industrial bitumen extraction processes corresponding to the tailings pond in this study are not contributing unique toxic substances to groundwater, relative to natural bitumen compounds present in groundwater flow systems.

Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma.

The accessibility of cell surface proteins makes them tractable for targeting by cancer immunotherapy, but identifying suitable targets remains challenging. Here we describe plasma membrane profiling of primary human myeloma cells to identify an unprecedented number of cell surface proteins of a primary cancer. We used a novel approach to prioritize immunotherapy targets and identified a cell surface protein not previously implicated in myeloma, semaphorin-4A (SEMA4A). Using knock-down by short-hairpin RNA and CRISPR/nuclease-dead Cas9 (dCas9), we show that expression of SEMA4A is essential for normal myeloma cell growth in vitro, indicating that myeloma cells cannot downregulate the protein to avoid detection. We further show that SEMA4A would not be identified as a myeloma therapeutic target by standard CRISPR/Cas9 knockout screens because of exon skipping. Finally, we potently and selectively targeted SEMA4A with a novel antibody-drug conjugate in vitro and in vivo.

Variation in septic system effluent inputs to tributaries in multiple subwatersheds and approaches to distinguish contributing pathways and areas.

Quantifying the contribution of septic systems to contaminant, including nutrient, loading to streams is needed in many watersheds to inform water quality management programs. However, this quantification is challenging due to the distributed locations of septic systems and uncertainties regarding the pathways delivering effluent from septic systems (functioning and failing) to a stream. The objectives of this study were firstly to evaluate how septic effluent inputs to streams vary with stream discharge conditions for multiple subwatersheds with different characteristics (i.e., geology, septic system density, and typical age), and secondly to examine new approaches for distinguishing the pathways and the contributing areas delivering septic effluent to streams. These approaches use the artificial sweetener acesulfame as a conservative tracer for septic effluent in applications of: (i) stream concentration-discharge (C-Q) relationships using low frequency sampling data, (ii) hysteresis behavior in event-based C-Q relationships, and (iii) longitudinal stream sampling. For all nine subwatersheds studied, the amount of septic effluent reaching the subwatershed outlets was considerably higher during high stream discharge (event) conditions compared to low discharge (baseflow) conditions, suggesting pathways other than groundwater may also be important. Generally, the percentage of septic effluent reaching the outlets was less for subwatersheds with newer households compared to those with older households. The combined interpretation of low frequency and event-based C-Q relationships indicate that complex pathways control the delivery of septic effluent to the subwatershed outlets. The interpretations suggest that groundwater pathways may dominate in some subwatersheds, while more rapid pathways associated with failing septic systems (e.g., overland runoff) may be important in others. Finally, longitudinal stream sampling illustrate the potential of acesulfame data to identify key areas contributing septic effluent to the stream. The novel approaches used here can be applied to guide future investigations aiming to quantify and manage water quality impairment from septic systems.

Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy.

Angiogenesis underlies development, physiology and pathogenesis of cancer, eye and cardiovascular diseases. Inhibiting aberrant angiogenesis using anti-angiogenic therapy (AAT) has been successful in the clinical treatment of cancer and eye diseases. However, resistance to AAT inevitably occurs and its molecular basis remains poorly understood. Here, we uncover molecular modifiers of the blood endothelial cell (EC) response to a widely used AAT bevacizumab by performing a pooled genetic screen using three-dimensional microcarrier-based cell culture and CRISPR-Cas9. Functional inhibition of the epigenetic reader BET family of proteins BRD2/3/4 shows unexpected mitigating effects on EC survival and/or proliferation upon VEGFA blockade. Moreover, transcriptomic and pathway analyses reveal an interaction between epigenetic regulation and anti-angiogenesis, which may affect chromosomal structure and activity in ECs via the cell cycle regulator CDC25B phosphatase. Collectively, our findings provide insight into epigenetic regulation of the EC response to VEGFA blockade and may facilitate development of quality biomarkers and strategies for overcoming resistance to AAT.

Organic contaminants of emerging concern in leachate of historic municipal landfills.

Many types of contaminants of emerging concern (CECs), including per- and poly-fluoroalkyl substances (PFAS), have been found in leachate of operating municipal landfills. However, there is only limited information on CECs presence in leachate of historic landfills (≥3 decades since closure, often lacking engineered liners or leachate collection systems) at concentrations that may pose a risk to nearby wells and surface water ecosystems. In this study, 48 samples of leachate-impacted groundwater were collected from 20 historic landfills in Ontario, Canada. The CECs measured included artificial sweeteners (ASs), PFAS, organophosphate esters (OPE), pharmaceuticals, bisphenols, sulfamic acid, perchlorate, and substituted phenols. The common presence of the AS saccharin, a known indicator of old landfill leachate, combined with mostly negligible levels of the AS acesulfame, an indicator of modern wastewater, revealed that most samples were strongly influenced by leachate and not cross-contaminated by wastewater (which can contain these same CECs). Several landfills, including ones closed in the 1960s, had total PFAS concentrations similar to those previously measured at modern landfills, with a maximum observed here of 12.7 µg/L. Notably elevated concentrations of several OPE, sulfamic acid, cotinine, and bisphenols A and S were found at many 30-60 year-old landfills. There was little indication of declining concentrations with landfill age, suggesting historic landfills can be long-term sources of CECs to groundwater and that certain CECs may be useful tracers for historic landfill leachate. These findings provide guidance on which CECs may require monitoring at historic landfill sites and wastewater treatment plants receiving their effluent.

Three's a crowd: A very rare form of polyorchidism with sertoli cell adenomas.

Polyorchidism is rare with fewer than 200 cases reported in literature. We present a case of a 26 year old male with chronic pain secondary to a very rare form of polyorchidism, with histology showing Sertoli cell adenomas. Orchiectomy should be considered in patients with chronic pain due to polyorchidism.

Female urethral stricture from chronic graft-versus-host disease.

Female urethral strictures are rare with limited literature to guide management. We present a case of a 27 year old female diagnosed with a urethral stricture secondary to chronic graft-versus-host disease. This diagnosis should be considered in females presenting with obstructive voiding symptoms and have risk factors for stricture development.

Non-target profiling of bitumen-influenced waters for the identification of tracers unique to oil sands processed-affected water (OSPW) in the Athabasca watershed of Alberta, Canada.

RATIONALE: The objective of this study was to identify unique chemical tracers of oil sands process-affected water (OSPW) to enable definitive discrimination of tailings pond seepage from natural bitumen-influenced waters from the Canadian Alberta McMurray formation. METHODS: The approach involved comparing unknowns from an unprecedented sample set of OSPW (n = 4) and OSPW-affected groundwaters (n = 15) with natural bitumen-influenced groundwaters (n = 20), using high-performance liquid chromatography/electrospray ionisation high-resolution mass spectrometry (HPLC/ESI-HRMS) operated in both polarities. RESULTS: Four unknown chemical entities were identified as potential tracers of OSPW seepage and subsequently subjected to structural elucidation. One potential tracer, tentatively identified as a thiophene-containing carboxylic acid [C15 H23 O3 S]- , was only detected in OSPW and OSPW-affected samples, thereby showing the greatest diagnostic potential. The remaining three unknowns, postulated to be two thiochroman isomers [C17 H25 O3 S]+ and an ethyl-naphthalene isomer [C16 H21 ]+ , were detected in one and two background groundwaters, respectively. CONCLUSIONS: We advanced the state of knowledge for tracers of tailings seepage beyond heteroatomic classes, to identifying diagnostic substances, with structures postulated. Synthesis of the four proposed structures is recommended to enable structural confirmations. This research will guide and inform the Oil Sands Monitoring Program in its efforts to assess potential influences of oil sands development on the Athabasca River watershed.

RYK-mediated filopodial pathfinding facilitates midgut elongation.

Between embryonic days 10.5 and 14.5, active proliferation drives rapid elongation of the murine midgut epithelial tube. Within this pseudostratified epithelium, nuclei synthesize DNA near the basal surface and move apically to divide. After mitosis, the majority of daughter cells extend a long, basally oriented filopodial protrusion, building a de novo path along which their nuclei can return to the basal side. WNT5A, which is secreted by surrounding mesenchymal cells, acts as a guidance cue to orchestrate this epithelial pathfinding behavior, but how this signal is received by epithelial cells is unknown. Here, we have investigated two known WNT5A receptors: ROR2 and RYK. We found that epithelial ROR2 is dispensable for midgut elongation. However, loss of Ryk phenocopies the Wnt5a-/- phenotype, perturbing post-mitotic pathfinding and leading to apoptosis. These studies reveal that the ligand-receptor pair WNT5A-RYK acts as a navigation system to instruct filopodial pathfinding, a process that is crucial for continuous cell cycling to fuel rapid midgut elongation.

Use of mature willows (Salix nigra) for hydraulic control of landfill-impacted groundwater in a temperate climate.

Phreatophytic trees such as willows and poplars have a large capacity for extracting shallow groundwater, as evidenced by diurnal water table fluctuations corresponding to intensified transpiration during the day. As a result, they have been employed for phytoremediation of shallow contaminated groundwater. In this study, the water extraction (i.e. pumping) capacity of mature willows (Salix nigra) to capture shallow polluted groundwater in Belle Park, the site of a former landfill in Kingston, Ontario (Canada), was assessed using continuous field measurements of sap flow and water table levels associated with a single willow tree, combined with a transient numerical model (FEFLOW). On an annual basis, the sapflow averaged 2.3 m3d-1, with 70% of the cumulative sap flow occurring during the active growing season (May to September). The calibration showed a good fit (0.91 < R2<0.97) between measured groundwater levels from three shallow wells installed near the willow and the calculated water table level fluctuations, thus confirming that the water extraction rate based on sap flow data for the willow was appropriate. At stand level, additional modelling suggests that 3.4-4.7 ha of mature willows (i.e. between 7.8% and 10.6% of the Park area), could compensate for the current water volumes extracted by the municipality using a conventional pump and treat system. The results of this study indicate that willows can play a significant role in capturing contaminated groundwater underlying Belle Park, and potentially at other sites where removal of contaminants from shallow aquifers is desired.

Advances in Distinguishing Groundwater Influenced by Oil Sands Process-Affected Water (OSPW) from Natural Bitumen-Influenced Groundwaters.

The objective of this study was to advance analytical methods for detecting oil sands process-affected water (OSPW) seepage from mining containments and discriminating any such seepage from the natural bitumen background in groundwaters influenced by the Alberta McMurray formation. Improved sampling methods and quantitative analyses of two groups of monoaromatic acids were employed to analyze OSPW and bitumen-affected natural background groundwaters for source discrimination. Both groups of monoaromatic acids showed significant enrichment in OSPW, while ratios of O2/O4 containing heteroatomic ion classes of acid extractable organics (AEOs) did not exhibit diagnostic differences. Evaluating the monoaromatic acids to track a known plume of OSPW-affected groundwater confirmed their diagnostic abilities. A secondary objective was to assess anthropogenically derived artificial sweeteners and per- and polyfluoroalkyl substances (PFAS) as potential tracers for OSPW. Despite the discovery of acesulfame and PFAS in most OSPW samples, trace levels in groundwaters influenced by general anthropogenic activities preclude them as individual robust tracers. However, their inclusion with the other metrics employed in this study served to augment the tiered, weight of evidence methodology developed. This methodology was then used to confirm earlier findings of OSPW migrations into groundwater reaching the Athabasca River system adjacent to the reclaimed pond at Tar Island Dyke.

Endobenthic Organisms Exposed to Chronically High Chloride from Groundwater Discharging along Freshwater Urban Streams and Lakeshores.

Chloride, especially from road salt, is one of the most ubiquitous contaminants of urban groundwater in temperate climates. The discharge of chloride-laden groundwater to freshwater ecosystems may pose a heightened risk to endobenthic organisms (buried in sediments), which may experience high concentrations prior to dilution from the overlying water. However, available exposure data is limited. Presented here are 22 chloride data sets from 15 urban sites across Canada, encompassing >1300 samples of shallow discharging groundwater collected principally during summer through autumn. Over half of the sites had an average chloride concentration above the long-term aquatic life guideline (120 mg/L), while 14% of each site's samples, on average, surpassed the short-term guideline (640 mg/L). Chloride concentrations frequently varied substantially (even >1000 mg/L) between adjacent locations (mostly <20 m separation), indicating patchy exposure. Chloride/bromide ratios, artificial sweeteners, and other tracers suggest a predominant contribution from road salt, with wastewater and landfill leachate important at some sites. Overall, these concentrations exceed those typically reported for urban wells and streams (even during the snowmelt period) in similar climates. These findings suggest that high chloride concentrations in shallow groundwater, largely from road salt, present a long-term threat to endobenthic organisms of urban surface waters in cold-region countries.

Endoscopic technique for closure of enterocutaneous fistulas.

BACKGROUND AND OBJECTIVES: Endoscopic over the scope clip (OTSC) closure represents a new technique for endoscopic management of enteric bleeding and tissue defects such as anastomotic leaks and enterocutaneous (EC) fistulas. We aim to describe our technical approach for OTSC closure of EC fistulas and convey our outcomes. METHODS AND PROCEDURES: This retrospective review includes ten patients who underwent OTSC application for EC fistulas by surgical endoscopists at a US tertiary care hospital from July 2015 to October 2017. Demographic data, along with type of defect, location, duration of lesion, success or failure of OTSC, and nutritional status were compiled. The ACS NSQIP surgical risk calculator was used to project the risk of mortality, complications, length of stay, and risk of readmission had our patients undergone surgical correction of their fistula. RESULTS: Overall success for EC fistula closure was 70%. Acute fistulas were closed with a success rate of 86%. Chronic fistulas were closed successfully in only 33% of cases. Of patients successfully closed, NSQIP-predicted rates of mortality, any complication, and median length of stay were 21.1%, 34.5%, and 9.5 days, respectively. With OTSC, these patients experienced 0 mortalities, 0 complications, and had a median length of stay of 4 days. CONCLUSION: OTSC is an effective adjunctive measure to improving rates of successful closure of EC fistulas and compromised anastomosis. OTSC conveys a markedly improved procedural risk profile as compared to standard surgical correction.

Transcatheter Valve-in-Valve Therapy Using a Balloon Expanding Valve for Treatment of Aortic Paravalvular Leakage.

Aortic paravalvular leakage (PVL) is a recognised complication of surgically replaced valves which is often treated using vascular plugs. Whilst transcatheter valve-in-valve therapy has been increasingly used for failed surgical bioprostheses, it is not considered as a treatment option for aortic PVL. However, the newer design of transcatheter aortic valves has a fabric skirt to create a more effective seal around the annulus. To our best knowledge, for the first time, we report successful adoption of the valve-in-valve therapy for the treatment of PVL in surgical bioprosthetic aortic valves such that the fabric skirt is placed immediately below the regurgitant orifice resulting in significant reduction in the PVL.

Prevalence of moderate-to-severe TR suitable for percutaneous intervention in TTE patients.

Moderate-to-severe tricuspid regurgitation is associated with higher mortality and morbidity yet remains significantly undertreated. The reasons for this are complex but include a higher operative mortality for patients undergoing isolated tricuspid valve surgery. This study sought to determine the prevalence of patients with moderate-to-severe tricuspid regurgitation and identify those who could be potentially suitable for percutaneous tricuspid valve intervention by screening patients referred for transthoracic echocardiography (ECHO) at a tertiary center. Our results showed that the prevalence of moderate-to-severe tricuspid regurgitation in our total ECHO patient population was 2.8%. Of these, approximately 1 in 8 patients with moderate-to-severe tricuspid regurgitation would be potentially suitable for percutaneous intervention, and suggests a large, unmet clinical need in this population.