Water quality impacts and river system recovery following the 2014 Mount Polley mine tailings dam spill, British Columbia, Canada

The Mount Polley mine tailings embankment breach on August 4th 2014, in British Columbia, Canada, is the second largest mine waste spill on record. The mine operator responded swiftly by removing significant quantities of tailings from the primary receiving watercourse, stabilizing the river corridor and beginning construction of a new river channel. This presented a unique opportunity to study spatial patterns of element cycling in a partially-restored and alkaline river system. Overall, water quality impacts are considered low with Cu, and to a lesser extent V, being the only elements of concern. However, the spatial pattern of stream Cu loading suggested chemical (dominant at low flow) and physical (dominant at high flow) mobilization processes operating in different parts of the watershed. Chemical mobilization was hypothesized to be due to Cu sulfide (chalcopyrite) oxidation in riparian tailings and reductive dissolution of Cu-bearing Fe oxides in tailings and streambed sediments whereas physical mobilization was due to erosion and suspension of Cu-rich stream sediments further downstream. Although elevated aqueous Cu was evident in Hazeltine Creek, this is considered a relatively minor perturbation to a watershed with naturally elevated stream Cu concentrations. The alkaline nature of the tailings and the receiving watercourse ensures most aqueous Cu is rapidly complexed with dissolved organic matter or precipitates as secondary mineral phases. Our data highlights how swift removal of spilled tailings and river corridor stabilization can limit chemical impacts in affected watersheds but also how chemical mobilization (of Cu) can still occur when the spilled tailings and the receiving environment are alkaline. We present a conceptual model of Cu cycling in the Hazeltine Creek watershed.publishersversionPeer reviewe

Pathways for nutrient loss to water with emphasis on phosphorus

Teagasc wishes to acknowledge the support of the Environmental Research Technological Development and Innovation (ERTDI) Programme under the Productive Sector Operational Programme which was financed by the Irish Government under the National Development Plan 2000-2006.End of project reportThe main objective of this project was to study phosphorus (P) loss from agricultural land under a range of conditions in Ireland, to quantify the main factors influencing losses and make recommendations on ways to reduce these losses. This report is a synthesis of the main conclusions and recommendations from the results of the studies. The final reports from the individual sub-projects in this project are available from the EPA (www.epa.ie).Environmental Protection Agenc

Human responses to Florida red tides : policy awareness and adherence to local fertilizer ordinances

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Science of The Total Environment 493 (2014): 898-909, doi:10.1016/j.scitotenv.2014.06.083.To mitigate the damages of natural hazards, policy responses can be beneficial only if they are effective. Using a self-administered survey approach, this paper focuses on the adherence to local fertilizer ordinances (i.e., county or municipal rules regulating the application of fertilizer to private lawns or facilities such as golf courses) implemented in jurisdictions along the southwest Florida coast in response to hazardous blooms of Florida red tides (Karenia brevis). These ordinances play a role in the context of evolving programs of water pollution control at federal, state, water basin, and local levels. With respect to policy effectiveness, while the strength of physical linkages is of critical importance, the extent to which humans affected are aware of and adhere to the relevant rules, is equally critical. We sought to understand the public’s depth of understanding about the rationales for local fertilizer ordinances. Respondents in Sarasota, Florida, were asked about their fertilizer practices in an area that has experienced several major blooms of Florida red tides over the past two decades. A highly educated, older population of 305 residents and “snowbirds” reported relatively little knowledge about a local fertilizer ordinance, its purpose, or whether it would change the frequency, size, or duration of red tides. This finding held true even among subpopulations that were expected to have more interest in or to be more knowledgeable about harmful algal blooms. In the face of uncertain science and environmental outcomes, and with individual motivations at odds with evolving public policies, the effectiveness of local community efforts to decrease the impacts of red tides may be compromised. Targeted social-science research on human perceptions about the risks of Florida red tides and education about the rationales for potential policy responses is warranted.This work was funded under sponsorship of the National Science Foundation (NSF), awards #1009106 and #1004181and the National Institute for Environmental Health Sciences (NIEHS), award # R21ES017413-01A2. Fleming received support from the European Regional Development Fund and European Social Fund (European Centre for Environment and Human Health, University of Exeter Medical School)

Advancing DNA barcoding and metabarcoding applications for plants requires systematic analysis of herbarium collections-an Australian perspective

Building DNA barcode databases for plants has historically been ad hoc, and often with a relatively narrow taxonomic focus. To realize the full potential of DNA barcoding for plants, and particularly its application to metabarcoding for mixed-species environmental samples, systematic sequencing of reference collections is required using an augmented set of DNA barcode loci, applied according to agreed data generation and analysis standards. The largest and most complete reference collections of plants are held in herbaria. Australia has a globally significant flora that is well sampled and expertly curated by its herbaria, coordinated through the Council of Heads of Australasian Herbaria. There exists a tremendous opportunity to provide a comprehensive and taxonomically robust reference database for plant DNA barcoding applications by undertaking coordinated and systematic sequencing of the entire flora of Australia utilizing existing herbarium material. In this paper, we review the development of DNA barcoding and metabarcoding and consider the requirements for a robust and comprehensive system. We analyzed the current availability of DNA barcode reference data for Australian plants, recommend priority taxa for database inclusion, and highlight future applications of a comprehensive metabarcoding system. We urge that large-scale and coordinated analysis of herbarium collections be undertaken to realize the promise of DNA barcoding and metabarcoding, and propose that the generation and curation of reference data should become a national investment priority

Obesity dysregulates the pulmonary antiviral immune response

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals

Relationships between neuronal oscillatory amplitude and dynamic functional connectivity

Event related fluctuations of neural oscillatory amplitude are reported widely in the context of cognitive processing and are typically interpreted as a marker of brain ‘activity’. However, the precise nature of these effects remains unclear; in particular, whether such fluctuations reflect local dynamics, integration between regions, or both, is unknown. Here, using magnetoencephalography (MEG), we show that movement induced oscillatory modulation is associated with transient connectivity between sensorimotor regions. Further, in resting state data, we demonstrate a significant association between oscillatory modulation and dynamic connectivity. A confound with such empirical measurements is that increased amplitude necessarily means increased signal to noise ratio (SNR): this means that the question of whether amplitude and connectivity are genuinely coupled, or whether increased connectivity is observed purely due to increased SNR is unanswered. Here we counter this problem by analogy with computational models which show that, in the presence of global network coupling and local multistability, the link between oscillatory modulation and long range connectivity is a natural consequence of neural networks. Our results provide evidence for the notion that connectivity is mediated by neural oscillations, and suggest that time-frequency spectrograms are not merely a description of local synchrony but also reflect fluctuations in long range connectivity

Factors influencing the approaches to studying of preclinical and clinical students and postgraduate trainees

<p>Abstract</p> <p>Background</p> <p>Students can be classified into three categories depending on their approaches to studying; namely, deep approach (DA), strategic approach (SA) and surface apathetic or superficial approach (SAA). The aim of this study was to identify factors affecting the approaches to studying among Sri Lankan medical undergraduates and post graduate trainees and to analyze the change in the pattern of study skills with time and experience.</p> <p>Method</p> <p>Pre-clinical and clinical students of the Faculty of Medicine, University of Colombo and postgraduate trainees in Surgery at the National Hospital of Sri Lanka were invited to complete the Approaches and Study Skills Inventory for Students (ASSIST) questionnaire.</p> <p>Results</p> <p>A total of 187 pre clinical (M: F = 96:91), 124 clinical (M: F = 61:63) and 53 post graduate trainees (M: F = 50:3) participated in the study. Approaches of male and female students were similar. SA was significantly affected by age among the preclinical students (p = 0.01), but not in other groups. Among pre-clinical students, males preferred a teacher who supported understanding (p = 0.04) but females preferred a passive transmission of information (p < 0.001). This, too, was not visible among other groups. A linear regression performed on group (batch), gender, island rank at GCE Advance Level (AL) examination, self appraisal score and the preference scores of type of teacher only managed to explain 35% or less of variance observed for each approach in individual groups.</p> <p>Conclusion</p> <p>Different factors affect the approach to studying in different groups but these explain only a small fraction of the variance observed.</p

An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.

Funder: UnitaidRepurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase I trial in healthy adult participants was undertaken with high-dose nitazoxanide. Participants received 1,500 mg nitazoxanide orally twice-daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose, and schedule. Intensive pharmacokinetic (PK) sampling was undertaken day 1 and 5 with minimum concentration (Cmin ) sampling on days 3 and 7. Fourteen healthy participants were enrolled between February 18 and May 11, 2021. All 14 doses were completed by 10 of 14 participants. Nitazoxanide was safe and with no significant adverse events. Moderate gastrointestinal disturbance (loose stools or diarrhea) occurred in 8 participants (57.1%), with urine and sclera discoloration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self-limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on the first dose and maintained throughout. Nitazoxanide administered at 1,500 mg b.i.d. with food was safe with acceptable tolerability a phase Ib/IIa study is now being initiated in patients with COVID-19

Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells

A major challenge associated with biochemical and cellular analysis of pseudokinases is a lack of target-validated small-molecule compounds with which to probe function. Tribbles 2 (TRIB2) is a cancer-associated pseudokinase with a diverse interactome, including the canonical AKT signaling module. There is substantial evidence that human TRIB2 promotes survival and drug resistance in solid tumors and blood cancers and therefore is of interest as a therapeutic target. The unusual TRIB2 pseudokinase domain contains a unique cysteine-rich C-helix and interacts with a conserved peptide motif in its own carboxyl-terminal tail, which also supports its interaction with E3 ubiquitin ligases. We found that TRIB2 is a target of previously described small-molecule protein kinase inhibitors, which were originally designed to inhibit the canonical kinase domains of epidermal growth factor receptor tyrosine kinase family members. Using a thermal shift assay, we discovered TRIB2-binding compounds within the Published Kinase Inhibitor Set (PKIS) and used a drug repurposing approach to classify compounds that either stabilized or destabilized TRIB2 in vitro. TRIB2 destabilizing agents, including the covalent drug afatinib, led to rapid TRIB2 degradation in human AML cancer cells, eliciting tractable effects on signaling and survival. Our data reveal new drug leads for the development of TRIB2-degrading compounds, which will also be invaluable for unraveling the cellular mechanisms of TRIB2-based signaling. Our study highlights that small molecule–induced protein down-regulation through drug “off-targets” might be relevant for other inhibitors that serendipitously target pseudokinases