Growth of Coal Mining Operations in the Elk River Valley (Canada) Linked to Increasing Solute Transport of Se, NO3-, and SO42- into the Transboundary Koocanusa Reservoir (USA-Canada).

Koocanusa Reservoir (KOC) is a waterbody that spans the United States (U.S.) and Canadian border. Increasing concentrations of total selenium (Se), nitrate + nitrite (NO3-, nitrite is insignificant or not present), and sulfate (SO42-) in KOC and downstream in the Kootenai River (Kootenay River in Canada) are tied to expanding coal mining operations in the Elk River Watershed, Canada. Using a paired watershed approach, trends in flow-normalized concentrations and loads were evaluated for Se, NO3-, and SO42- for the two largest tributaries, the Kootenay and Elk Rivers, Canada. Increases in concentration (SO42- 120%, Se 581%, NO3- 784%) and load (SO42- 129%, Se 443%, NO3- 697%) in the Elk River (1979-2022 for NO3-, 1984-2022 for Se and SO42-) are among the largest documented increases in the primary literature, while only a small magnitude increase in SO42- (7.7% concentration) and decreases in Se (-10%) and NO3- (-8.5%) were observed in the Kootenay River. Between 2009 and 2019, the Elk River contributed, on average, 29% of the combined flow, 95% of the Se, 76% of the NO3-, and 38% of the SO42- entering the reservoir from these two major tributaries. The largest increase in solute concentrations occurred during baseflows, indicating a change in solute transport and delivery dynamics in the Elk River Watershed, which may be attributable to altered landscapes from coal mining operations including altered groundwater flow paths and increased chemical weathering in waste rock dumps. More recently there is evidence of surface water treatment operations providing some reduction in concentrations during low flow times of year; however, these appear to have a limited effect on annual loads entering KOC. These findings imply that current mine water treatment, which is focused on surface waters, may not sufficiently reduce the influence of mine-waste-derived solutes in the Elk River to allow constituent concentrations in KOC to meet U.S. water-quality standards.

Long-Term Changes in Sediment and Nutrient Delivery from Conowingo Dam to Chesapeake Bay: Effects of Reservoir Sedimentation.

Reduction of suspended sediment (SS), total phosphorus (TP), and total nitrogen is an important focus for Chesapeake Bay watershed management. The Susquehanna River, the bay's largest tributary, has drawn attention because SS loads from behind Conowingo Dam (near the river's mouth) have been rising dramatically. To better understand these changes, we evaluated histories of concentration and loading (1986-2013) using data from sites above and below Conowingo Reservoir. First, observed concentration-discharge relationships show that SS and TP concentrations at the reservoir inlet have declined under most discharges in recent decades, but without corresponding declines at the outlet, implying recently diminished reservoir trapping. Second, best estimates of mass balance suggest decreasing net deposition of SS and TP in recent decades over a wide range of discharges, with cumulative mass generally dominated by the 75∼99.5th percentile of daily Conowingo discharges. Finally, stationary models that better accommodate effects of riverflow variability also support the conclusion of diminished trapping of SS and TP under a range of discharges that includes those well below the literature-reported scour threshold. Overall, these findings suggest that decreased net deposition of SS and TP has occurred at subscour levels of discharge, which has significant implications for the Chesapeake Bay ecosystem.

UBL1 of Fusarium verticillioides links the N-end rule pathway to extracellular sensing and plant pathogenesis.

Fusarium verticillioides produces fumonisin mycotoxins during colonization of maize. Currently, molecular mechanisms underlying responsiveness of F.verticillioides to extracellular cues during pathogenesis are poorly understood. In this study, insertional mutants were created and screened to identify genes involved in responses to extracellular starch. In one mutant, the restriction enzyme-mediated integration cassette disrupted a gene (UBL1) encoding a UBR-Box/RING domain E3 ubiquitin ligase involved in the N-end rule pathway. Disruption of UBL1 in F.verticillioides (Δubl1) influenced conidiation, hyphal morphology, pigmentation and amylolysis. Disruption of UBL1 also impaired kernel colonization, but the ratio of fumonisin B1 per unit growth was not significantly reduced. The inability of a Δubl1 mutant to recognize an N-end rule degron confirmed involvement of UBL1 in the N-end rule pathway. Additionally, Ubl1 physically interacted with two G protein α subunits of F.verticillioides, thus implicating UBL1 in G protein-mediated sensing of the external environment. Furthermore, deletion of the UBL1 orthologue in F.graminearum reduced virulence on wheat and maize, thus indicating that UBL1 has a broader role in virulence among Fusarium species. This study provides the first linkage between the N-end rule pathway and fungal pathogenesis, and illustrates a new mechanism through which fungi respond to the external environment.

Azithromycin suppresses human osteoclast formation and activity in vitro.

Azithromycin is an antibiotic with anti-inflammatory properties used as an adjunct to treat periodontitis, a common inflammatory mediated condition featuring pathologic alveolar bone resorption. This study aimed to determine the effect of azithromycin on human osteoclast formation and resorptive activity in vitro. Osteoclasts were generated from peripheral blood mononuclear cells stimulated with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B (RANK) ligand. The effects of azithromycin at concentrations ranging from 0.5 to 40 µg/ml were tested. Osteoclast formation and activity, acidification, actin ring formation and expression of mRNA, and protein encoding for key osteoclast genes were assessed. The results demonstrated that azithromycin reduced osteoclast resorptive activity at all concentrations tested with osteoclast formation being significantly reduced at the higher concentrations (20 and 40 µg/ml). mRNA and protein expression of key osteoclast transcription factor Nuclear Factor of Activated T cells (NFATc1) was significantly reduced by azithromycin at later stages of osteoclast development (day 17). Azithromycin also reduced tumor necrosis factor receptor associated factor-6 (TRAF6) mRNA expression at day 14, and cathepsin K mRNA expression at days 14 and 17. Integrin ß3 and MMP-9 mRNA expression was reduced by azithromycin at day 17 in osteoclasts cultured on dentine. The osteoclast proton pump did not appear to be affected by azithromycin, however formation of the actin ring cytoskeleton was inhibited. This study demonstrates that azithromycin inhibits human osteoclast function in vitro, which may account for at least some of the beneficial clinical effects observed with azithromycin treatment in periodontitis.

Nitrate in the Mississippi River and its tributaries, 1980 to 2008: are we making progress?

Changes in nitrate concentration and flux between 1980 and 2008 at eight sites in the Mississippi River basin were determined using a new statistical method that accommodates evolving nitrate behavior over time and produces flow-normalized estimates of nitrate concentration and flux that are independent of random variations in streamflow. The results show that little consistent progress has been made in reducing riverine nitrate since 1980, and that flow-normalized concentration and flux are increasing in some areas. Flow-normalized nitrate concentration and flux increased between 9 and 76% at four sites on the Mississippi River and a tributary site on the Missouri River, but changed very little at tributary sites on the Ohio, Iowa, and Illinois Rivers. Increases in flow-normalized concentration and flux at the Mississippi River at Clinton and Missouri River at Hermann were more than three times larger than at any other site. The increases at these two sites contributed much of the 9% increase in flow-normalized nitrate flux leaving the Mississippi River basin. At most sites, concentrations increased more at low and moderate streamflows than at high streamflows, suggesting that increasing groundwater concentrations are having an effect on river concentrations.

Weighted Regressions on Time, Discharge, and Season (WRTDS), with an Application to Chesapeake Bay River Inputs.

A new approach to the analysis of long-term surface water-quality data is proposed and implemented. The goal of this approach is to increase the amount of information that is extracted from the types of rich water-quality datasets that now exist. The method is formulated to allow for maximum flexibility in representations of the long-term trend, seasonal components, and discharge-related components of the behavior of the water-quality variable of interest. It is designed to provide internally consistent estimates of the actual history of concentrations and fluxes as well as histories that eliminate the influence of year-to-year variations in streamflow. The method employs the use of weighted regressions of concentrations on time, discharge, and season. Finally, the method is designed to be useful as a diagnostic tool regarding the kinds of changes that are taking place in the watershed related to point sources, groundwater sources, and surface-water nonpoint sources. The method is applied to datasets for the nine large tributaries of Chesapeake Bay from 1978 to 2008. The results show a wide range of patterns of change in total phosphorus and in dissolved nitrate plus nitrite. These results should prove useful in further examination of the causes of changes, or lack of changes, and may help inform decisions about future actions to reduce nutrient enrichment in the Chesapeake Bay and its watershed.Hirsch, Robert M., Douglas L. Moyer, and Stacey A. Archfield, 2010. Weighted Regressions on Time, Discharge, and Season (WRTDS), With an Application to Chesapeake Bay River Inputs. Journal of the American Water Resources Association (JAWRA) 46(5):857-880. DOI: 10.1111/j.1752-1688.2010.00482.x.

The correlation between elevated cardiac troponin I and pulmonary artery obstruction index in ED patients with pulmonary embolism.

OBJECTIVES: The aim of this study is to investigate the correlation between cardiac troponin I (cTnI) values and the pulmonary artery obstruction index assessed with spiral computed tomography (CT) scan in emergency department (ED) patients with pulmonary embolism (PE). METHODS: This is a retrospective cohort study of all 179 ED patients diagnosed with PE between December 2004 and January 2007. Study population consisted of 104 (58.1%) of 179 patients with PE in whom both cTnI was measured and a contemporaneously performed CT scan was available for review. In these patients, the levels of cTnI measured in the ED were correlated with the degree of pulmonary vascular obstruction determined by applying the modified Computed Tomography Obstruction Index to the spiral CT scan performed in the ED. RESULTS: Troponin values were elevated in 20 (19.2%) of 104 patients (95% confidence interval [CI], 11.6-26.8) with a mean cTnI concentration of 0.38 +/- 0.44 microg/L. Elevated cTnI value had a significant correlation with main pulmonary arteries involvement using the modified Computed Tomography Obstruction Index score (P = .0001). Elevated ED cTnI value had 53.8% (95% CI, 37.6-66) sensitivity and 92.3% (95% CI, 87-96.4) specificity, 70% (95% CI, 49-86) PPV, and 85.7% (95% CI, 80.7-90) NPV for predicting main pulmonary artery obstruction on CT. Increased cTnI values were highly correlated to intensive care unit admission of patients with PE (RR, 12.83; 95% CI, 3.87-42.4). CONCLUSIONS: Measuring cTnI value might be considered in ED patients who are suspected of having PE. Elevated cTnI should raise the clinician's concern for the possibility of central pulmonary vascular obstruction.

Point sources and agricultural practices control spatial-temporal patterns of orthophosphate in tributaries to Chesapeake Bay.

Orthophosphate (PO4) is the most bioavailable form of phosphorus (P). Excess PO4 may cause harmful algal blooms in aquatic ecosystems. A major restoration effort is underway for Chesapeake Bay (CB) to reduce P, nitrogen, and sediment loading to CB. Although PO4 cycling and delivery to streams has been characterized in small-scale studies, regional drivers of PO4 patterns remain poorly understood because most water quality trend assessment focus on total P. Moreover, these trend assessments are usually at an annual timestep. To address this research gap, we analyzed PO4 patterns over a 9-year period at 53 monitoring stations across the CB watershed to: 1) characterize the role of PO4 in total P fluxes and trends; 2) describe spatial and temporal patterns of PO4 concentrations across seasons and streamflow; and 3) explore factors explaining these patterns. Agricultural watersheds exported the most total P compared with watersheds under different land uses (e.g., urban or forest), with PO4 comprising up to 50% of those exports. Although PO4 exports are declining at many sites, some agricultural regions are experiencing increasing trends at a rate sufficient to drive total P trends. Regression modeling results suggest that point source load reductions are likely responsible for decreasing PO4 concentrations observed at many sites. Watersheds with more Conservation Reserve Program enrollment had lower summer PO4 concentrations, highlighting the effectiveness of this practice. Manure inputs strongly predicted PO4 concentrations at high flows across all seasons. Both manure applications and conservation tillage were correlated with changes in PO4 concentrations at high flow, suggesting these activities could contribute to increasing PO4 concentrations. This study highlights the effectiveness of point source control for reducing PO4 exports and underscores the need for management strategies to target sources, practices, and landscape factors determining PO4 loss from soils where manure inputs remain high.

Phosphorus and the Chesapeake Bay: Lingering Issues and Emerging Concerns for Agriculture.

Hennig Brandt's discovery of phosphorus (P) occurred during the early European colonization of the Chesapeake Bay region. Today, P, an essential nutrient on land and water alike, is one of the principal threats to the health of the bay. Despite widespread implementation of best management practices across the Chesapeake Bay watershed following the implementation in 2010 of a total maximum daily load (TMDL) to improve the health of the bay, P load reductions across the bay's 166,000-km watershed have been uneven, and dissolved P loads have increased in a number of the bay's tributaries. As the midpoint of the 15-yr TMDL process has now passed, some of the more stubborn sources of P must now be tackled. For nonpoint agricultural sources, strategies that not only address particulate P but also mitigate dissolved P losses are essential. Lingering concerns include legacy P stored in soils and reservoir sediments, mitigation of P in artificial drainage and stormwater from hotspots and converted farmland, manure management and animal heavy use areas, and critical source areas of P in agricultural landscapes. While opportunities exist to curtail transport of all forms of P, greater attention is required toward adapting P management to new hydrologic regimes and transport pathways imposed by climate change.

Effectiveness of Practices to Support Appropriate Laboratory Test Utilization: A Laboratory Medicine Best Practices Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the effectiveness of practices used to support appropriate clinical laboratory test utilization. METHODS: This review followed the Centers for Disease Control and Prevention (CDC) Laboratory Medicine Best Practices A6 cycle method. Eligible studies assessed one of the following practices for effect on outcomes relating to over- or underutilization: computerized provider order entry (CPOE), clinical decision support systems/tools (CDSS/CDST), education, feedback, test review, reflex testing, laboratory test utilization (LTU) teams, and any combination of these practices. Eligible outcomes included intermediate, systems outcomes (eg, number of tests ordered/performed and cost of tests), as well as patient-related outcomes (eg, length of hospital stay, readmission rates, morbidity, and mortality). RESULTS: Eighty-three studies met inclusion criteria. Fifty-one of these studies could be meta-analyzed. Strength of evidence ratings for each practice ranged from high to insufficient. CONCLUSION: Practice recommendations are made for CPOE (specifically, modifications to existing CPOE), reflex testing, and combined practices. No recommendation for or against could be made for CDSS/CDST, education, feedback, test review, and LTU. Findings from this review serve to inform guidance for future studies.

River chloride trends in snow-affected urban watersheds: increasing concentrations outpace urban growth rate and are common among all seasons.

Chloride concentrations in northern U.S. included in this study have increased substantially over time with average concentrations approximately doubling from 1990 to 2011, outpacing the rate of urbanization in the northern U.S. Historical data were examined for 30 monitoring sites on 19 streams that had chloride concentration and flow records of 18 to 49 years. Chloride concentrations in most studied streams increased in all seasons (13 of 19 in all seasons; 16 of 19 during winter); maximum concentrations occurred during winter. Increasing concentrations during non-deicing periods suggest that chloride was stored in hydrologic reservoirs, such as the shallow groundwater system, during the winter and slowly released in baseflow throughout the year. Streamflow dependency was also observed with chloride concentrations increasing as streamflow decreased, a result of dilution during rainfall- and snowmelt-induced high-flow periods. The influence of chloride on aquatic life increased with time; 29% of sites studied exceeded the concentration for the USEPA chronic water quality criteria of 230 mg/L by an average of more than 100 individual days per year during 2006-2011. The rapid rate of chloride concentration increase in these streams is likely due to a combination of possible increased road salt application rates, increased baseline concentrations, and greater snowfall in the Midwestern U.S. during the latter portion of the study period.

Ongoing prospective multicenter safety study of the cytoprotectant amifostine given subcutaneously: overview of trial design.

The study is a prospective, open-label, multicenter safety study designed to identify treatment-related side effects of amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) administered as a subcutaneous injection for the prevention of radiation-induced toxicities. More than 100 patients (68 males, 33 females; median age, 64 years) received 500 mg of amifostine by subcutaneous injection before daily radiation therapy. Four types of targeted adverse events were examined as to their occurrence and possible relationship with amifostine. These adverse events included nausea/vomiting, local skin reactions, skin rashes, and hypotension.

Docetaxel and carboplatin as first-line therapy in advanced non-small cell lung carcinoma: a phase II study.

BACKGROUND: Taxanes have been widely used against advanced non-small cell lung cancer (NSCLC), alone and in combination with platinum agents. In order to develop a tolerable palliative regimen, we combined carboplatin with low dose docetaxel. PATIENTS AND METHODS: Chemotherapy-naive patients, with Stage IIIB or IV NSCLC and an ECOG performance status < or = 2, were enrolled. Treatment consisted of docetaxel 60 mg/m2 and carboplatin AUC 6 every 21 days. Therapy continued for 1 year or 6 months beyond best response, whichever was greater. RESULTS: Twenty-five patients were enrolled. Most patients (80%) had Stage IV disease. The partial response rate was 16%. Response duration ranged from 6 to 115 weeks. Median survival was 55 weeks. Toxicity was generally limited to grade 3 or 4 neutropenia. There was 1 septic death. CONCLUSION: Survival compared favorably to other similar trials employing higher doses of docetaxel. Additionally, a hematologic toxicity advantage was seen compared to regimens containing higher doses of docetaxel.

Agrobacterium tumefaciens-mediated transformation of the soybean pathogen Phomopsis longicolla.

To facilitate functional genomics in the soybean pathogen Phomopsis longicolla, we developed a robust Agrobacterium tumefaciens-mediated transformation system that yielded 150-250 transformants per 1×10(6) conidia of P. longicolla. This first report of P. longicolla transformation provides a useful tool for insertional mutagenesis in an increasingly important pathogen of soybean.

Radiographic recognition of dental implants as an aid to identifying the deceased.

This study was undertaken to determine if dental implants can be radiographically differentiated by company type to aid forensic identification of the deceased. Recognition of dental implants on intraoral radiographic images was assessed in a blind study using a radiographic examination guide to highlight differences between dental implants. Inter- and intra-examiner comparisons were conducted and a computer program (Implant Recognition System) was evaluated to see whether it improved the accuracy of implant recognition. The study found that dental implants could be radiographically differentiated by company type. The Implant Recognition System in its current form was of little benefit for radiographic assessment of dental implants for forensic odontologists. Prior knowledge of implant types, with a McNemar's statistical value of 92.9, proved to be most significant in identification.

Receptor activator NF kappaB ligand (RANKL) and osteoprotegerin (OPG) protein expression in periodontitis.

OBJECTIVES AND BACKGROUND: This study investigated the expression of key mediators that regulate differentiation of osteoclasts, receptor activator of nuclear factor kappaB ligand (RANKL), and its natural inhibitor, osteoprotegerin (OPG), in periodontitis. We aimed to compare the levels of the RANKL and OPG in the granulomatous tissue adjacent to areas of alveolar bone loss from patients with periodontitis to that present in tissue from patients without periodontitis. In addition, we aimed to determine the types of cells expressing these factors in these tissues and to demonstrate the expression of the osteoclastic markers, RANK and tartrate-resistant acid phosphatase (TRAP), in periodontitis. MATERIALS AND METHODS: Frozen biopsy specimens were analysed using specific monoclonal antibodies and were evaluated by semiquantitative analysis and digital image analysis to compare levels of RANKL and OPG protein expression. Double labelling of frozen sections with antibodies to different cell lineage specific markers was used to determine the types of cells expressing these proteins. In situ hybridization was used to detect cells expressing RANK mRNA. RESULTS: Semiquantitative image analysis demonstrated that significantly higher levels of RANKL protein (P < 0.05) were expressed in the periodontitis tissue. Conversely, OPG protein was significantly lower (P < 0.05) in the periodontitis tissues. RANKL protein was associated with lymphocytes and macrophages. OPG protein was associated with endothelial cells in both tissues. Many leukocytes expressing RANK mRNA and TRAP were observed in periodontitis tissues. CONCLUSION: The change in the levels of these key regulators of osteoclast differentiation may play a major role in the bone loss seen in periodontitis.