Selection of remedial alternatives for mine sites: a multicriteria decision analysis approach.

The selection of remedial alternatives for mine sites is a complex task because it involves multiple criteria and often with conflicting objectives. However, an existing framework used to select remedial alternatives lacks multicriteria decision analysis (MCDA) aids and does not consider uncertainty in the selection of alternatives. The objective of this paper is to improve the existing framework by introducing deterministic and probabilistic MCDA methods. The Preference Ranking Organization Method for Enrichment Evaluation (PROMETHEE) methods have been implemented in this study. The MCDA analysis involves processing inputs to the PROMETHEE methods that are identifying the alternatives, defining the criteria, defining the criteria weights using analytical hierarchical process (AHP), defining the probability distribution of criteria weights, and conducting Monte Carlo Simulation (MCS); running the PROMETHEE methods using these inputs; and conducting a sensitivity analysis. A case study was presented to demonstrate the improved framework at a mine site. The results showed that the improved framework provides a reliable way of selecting remedial alternatives as well as quantifying the impact of different criteria on selecting alternatives.

Predicting copper concentrations in acid mine drainage: a comparative analysis of five machine learning techniques.

Acid mine drainage (AMD) is a global problem that may have serious human health and environmental implications. Laboratory and field tests are commonly used for predicting AMD, however, this is challenging since its formation varies from site-to-site for a number of reasons. Furthermore, these tests are often conducted at small-scale over a short period of time. Subsequently, extrapolation of these results into large-scale setting of mine sites introduce huge uncertainties for decision-makers. This study presents machine learning techniques to develop models to predict AMD quality using historical monitoring data of a mine site. The machine learning techniques explored in this study include artificial neural networks (ANN), support vector machine with polynomial (SVM-Poly) and radial base function (SVM-RBF) kernels, model tree (M5P), and K-nearest neighbors (K-NN). Input variables (physico-chemical parameters) that influence drainage dynamics are identified and used to develop models to predict copper concentrations. For these selected techniques, the predictive accuracy and uncertainty were evaluated based on different statistical measures. The results showed that SVM-Poly performed best, followed by the SVM-RBF, ANN, M5P, and KNN techniques. Overall, this study demonstrates that the machine learning techniques are promising tools for predicting AMD quality.

An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression.

Research over the last two decades has established ketamine as a safe, effective, fast-acting, and sustained antidepressant that significantly reduces adverse symptoms associated with depression, even in patients who are treatment resistant. Much of this research has evolved within the framework of several independent branches of scientific inquiry: in addition to the study of ketamine is a non-selective NMDAR antagonist with rapid antidepressant effects, it has also been found effective as a psychoplastogen that stimulates synaptogenesis and increases neuroplasticity, as a powerful anti-inflammatory that may improve inflammation-related depressive symptoms, as a substance that induces beneficial high entropy brain states, and as a subjectively impactful psychedelic agent. Each branch of inquiry has generated independent evidence of ketamine's efficacy but has advanced without substantive coordination or communication with other lines of inquiry. Integrative research that considers these branches of research together may lead toward a better understanding of ketamine's effects and improved treatment protocols and clinical outcomes. Such an overview can inform more comprehensive patient care through: (a) informed patient psychoeducation that encompasses all of ketamine's mechanisms of action; (b) calibration of optimal dosage to ensure induction and maintenance of high entropy brain states during each ketamine session utilizing EEG measurement; (c) Improved management of emergence side effects through proper care for set and setting; (d) inclusion of pre-selected appropriate music to enhance the emotional experience; (e) increased monitoring of ketamine effects on cortical activity, inter-hemispheric imbalance, and inflammation-related levels of cytokines to further improvements in ketamine protocols; and (f) appropriate timing of any adjunctive psychotherapy sessions to coincide with peak neurogenesis at 24-48 h post ketamine treatment.

Prediction of acid rock drainage in waste rock piles part 2: Water flow patterns and leaching process.

In waste rock piles, the leaching process involved in acid rock drainage is mainly controlled by water flow. This paper (Part 2) investigates the effects of heterogeneities on the water flow patterns by applying probability density functions to hydrogeological properties. In this study, a piecewise constant distribution is proposed to describe the permeability inside waste rock piles, which reflects the effect of both finer and coarser pores. Compared with uniform water flow obtained from traditional homogeneous modeling, various water flow patterns and their pathways inside waste rock piles can be simulated by the proposed model. In addition, the leaching process is also investigated by coupling the calculated water flow with the geochemical reaction based on the water film model proposed in part 1. For demonstration, these models are integrated and applied to the full-scale waste rock pile at Equity Silver mine in British Columbia, Canada. Because the iron loading is highly correlated to the acidity at this site, it is found that the fluctuation of annual lime consumption for neutralization at this site can be well predicted by the integrated model. In addition, the results indicate that waste rock piles with different spatial patterns of permeability distribution, but with the same probability density function, may have different water flow patterns and spatial distributions of iron concentrations inside the pile. However, the total water flow discharge rate and iron loading profiles from the pile are almost the same on the temporal scale.

The correlation between drainage chemistry and weather for full-scale waste rock piles based on artificial neural network.

In this paper, a machine learning algorithm based on artificial neural network architecture investigates the correlation between drainage chemistries in seepage water and ambient weather conditions around waste rock piles. The proposed neural network consists of a long short-term memory unit and a fully connected neural network which uses sequenced input to consider current and previous weather impact on the drainage chemistries. A 20-year (1998-2017) monitoring database obtained from the full-scale waste rock pile of the Equity Silver mine in BC, Canada is used for validating the proposed approach. The neural network is trained based on total precipitation and mean temperature as input and the acidity as output. The results indicate that the calculated acidity from the trained neural network matches with that measured in the field well. In addition, the accuracy of calculated acidity can be further increased by adding a time tag of acidity measurement date into the input layer. This refined approach can capture the long-term evolution and dynamics of hydrogeochemical and biochemical properties inside the waste rock piles.

Ketamine-Assisted and Culturally Attuned Trauma Informed Psychotherapy as Adjunct to Traditional Indigenous Healing: Effecting Cultural Collaboration in Canadian Mental Health Care.

Ketamine therapy with culturally attuned trauma-informed psychotherapy in a collaborative cross-cultural partnership may provide a critical step in the operationalization and optimization of treatment effectiveness in diverse populations and may provide a foundation for an improved quality of life for Indigenous people. Decolonizing Indigenous health and wellbeing is long overdue, requiring an equal partnership between government and Indigenous communities, built upon an aboriginal culture holistic foundation of balance of mind, body, social and spiritual realms, and within the context of historical and lived experiences of colonialism. Culturally attuned trauma-informed psychotherapy paired with ketamine-a fast-acting antidepressant that typically takes effect within 4 hours, even in cases of acute suicidality-may be uniquely qualified to integrate into an Indigenous based health system, since ketamine's therapeutic effects engage multiple neuropsychological, physiological, biological, and behavioral systems damaged by intergenerational complex developmental trauma. Ketamine holds the potential to serve as a core treatment modality around which culturally engaged treatment approaches might be organized since its brief alteration of normal waking consciousness is already a familiar and intrinsic element of healing culture in many Indigenous societies. There is great need and desire in Indigenous communities for respectful and sacred partnership in fostering more effective mental health outcomes and improved quality of life.

Retrospective Observational Study of Daytime Add-On Administration of Zopiclone to Difficult-to-Treat Psychiatric Inpatients With Unpredictable Aggressive Behavior, With or Without EEG Dysrhythmia.

Managing violent behavior is a particularly challenging aspect of hospital psychiatric care. Available pharmacological interventions are often unsatisfactory. Aim: To assess the effectiveness and safety of daytime zopiclone add-on administration in violent and difficult-to-treat psychiatric inpatients. Methods: Chart review of inpatients treated with daytime zopiclone, between 2014 and 2018, with up to 12 weeks follow-up. Effectiveness was retrospectively assessed with the Clinical Global Impression rating scale (CGI) and the frequency and severity of aggressive incidents recorded with the Staff Observation Aggression Scale-Revised (SOAS-R). Results: Forty-five (30 male, 15 female) cases, 18-69 years age range, average (SD) baseline CGI-S score of 5.4 (1.0), and a variety of diagnoses. Sixty-nine percent showed CGI-S improvement of any degree. For patients with at least one aggressive incident within 7 days prior to initiation of zopiclone (N = 22), average (SD) SOAS-R-Severity LOCF to baseline change was -3.5 (2.7) P < 0.0001. Most patients reported no side effects; 24% reported one or more side effects, and 11% discontinued zopiclone due to sedation (4), insomnia (1) or slurred speech (1). No SAEs were recorded. Zopiclone maximum daily dose correlated with CGI-S baseline-to-LOCF change (rho = -0.5, P = 0.0003). The ROC AUC of zopiclone maximum daily dose and improvement on CGI-S was 0.84 (95% CI 0.70-0.93, P < 0.0001). The ROC AUC of zopiclone maximum daily dose and SOAS-R-N improvement was 0.80 (95% CI 0.58-0.92; P = 0.0008) and maximum Youden's index value was achieved at a dose of >30 mg. Conclusions: Zopiclone doses >30 mg daily achieved the best anti-aggressive effect.

Prediction of acid rock drainage in waste rock piles Part 1: Water film model for geochemical reactions and application to a full-scale case study.

Geochemical reactions taking place at the rock surface and pore water interface, and rapid preferential water flow through waste rock piles are identified as two primary steps for acid rock drainage (ARD) and metal leaching (ML) processes. This paper (Part I) develops a water film model to describe the interactions among sulphide minerals, pore water and oxygen, which considers the reactive surface areas as the primary sites to capture geochemical reactions including sulphide oxidation and neutralization reactions, and also considers acid and metal ion storage in pore water. In addition, the proposed water film model is further coupled with a pile-scale mass transport model to investigate a specific case of the main waste rock pile at the Equity Silver mine, Canada. Overall, the simulated profile of oxygen concentration matches the historical monitoring data. The modeling results revealed potential controlling mechanisms for ARD generation inside the waste rock pile and provided insights into the impact of an engineered cover on the waste rock pile.

The characteristic properties of waste rock piles in terms of metal leaching.

Surface/ground waters could be polluted when rain-water and/or snow-melt water infiltrate through waste rock piles at mine sites and dissolve secondary minerals (salts) from rock surfaces. It is important to reduce solute loading by the optimal configuration of waste rock piles. This requires the proper definition and determination of the characteristic properties of waste rock piles in terms of metal leaching and, in particular, rate control mechanisms and scaling laws, and their dependence upon configuration variables. For revealing these characteristic properties this paper proposes a pile-scale C-Q relation: C = Cs(1 - e-P/Q), (P ≡ kλßψ), where C and Cs are respectively solute concentration and particle's saturation concentration, Q is the flow rate of the water through a waste rock pile, k represents the effective or average dissolution coefficient of a mineral specie from rock surfaces, ß represents rock pile depth, λ represents the ratio of the sum of the surface areas of rocks to the volume that the rocks occupy, and ψ is the sum of the cross-sections of water-flow channels in a waste rock pile. The two characteristic properties revealed by the C-Q relation are: (1) P, the product of k, λ, ß, and ψ (P ≡ kλßψ), which is the characteristic property of a waste rock pile in terms of metal leaching, named here the solute production potential; and (2) the ratio of P to Q, P/Q, a non-dimensional number, designated as α (α ≡ P/Q), named here the rate control quotient, which is the scaling law and the rate control mechanism indicator. The value of α quantitatively indicates what controls the rate of mineral dissolution, and it also relates smaller-scale metal-leaching testing results to their corresponding full scales. When α becomes small, say α < 0.5, the rate of solute production potential P becomes in control, and the solute loading is nearly independent of Q; when α becomes larger, say α > 2.5, solute concentration would become close to its saturation concentration Cs, and Q determines solute loading (that is, the solute loading is proportional to Q). When 0.5 < α < 2.5, both Q and P are in control, a mixed control mechanism. The 20 years of measurements of mine drainage chemistry from the main waste rock piles at the Equity Silver mine, BC, Canada, are used to illustrate how to determine the two characteristic properties P and α, and how well they are able to describe the waste rock piles in terms of metal leaching.

Environmental risk assessment of acid rock drainage under uncertainty: The probability bounds and PHREEQC approach.

Acid rock drainage (ARD) is a major environmental problem that poses significant environmental risks during and after mining activities. A new methodology for environmental risk assessment based on probability bounds and a geochemical speciation model (PHREEQC) is presented. The methodology provides conservative and non-conservative ways of estimating risk of heavy metals posed to selected endpoints probabilistically, while propagating data and parameter uncertainties throughout the risk assessment steps. The methodology is demonstrated at a minesite located in British Columbia, Canada. The result of the methodology for the case study minesite shows the fate-and-transport of heavy metals is well simulated in the mine environment. In addition, the results of risk characterization for the case study show that there is risk due to transport of heavy metals into the environment.

A human osteosarcoma cell line expressing herpes simplex type-1 thymidine kinase: studies with radiolabeled (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine.

INTRODUCTION: (E)-5-(2-Iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) is a pyrimidine nucleoside analogue that accumulates selectively in murine cells expressing herpes simplex type-1 thymidine kinase (HSV-1 TK). The uptake of [(125)I]IVFRU in human 143B osteosarcoma cells transduced with a retroviral vector bearing the HSV-1 TK gene (143B-LTK cells) is now reported. METHODS: HSV-1 TK gene expression in 143B-LTK cells was confirmed by Western blotting and reverse transcriptase (RT)-PCR. Cell and subcellular uptake of [(125)I]IVFRU was determined in cell culture, and whole body biodistribution after intravenous injection of [(125)I]IVFRU was determined using nude mice bearing implanted 143B or 143B-LTK tumors. RESULTS: Although IVFRU was less toxic to the human cell line expressing HSV-1 TK (143B-LTK) than ganciclovir, both IVFRU and ganciclovir were not toxic to the cell line not expressing HSV-1 TK (143B). When cells were exposed to [(125)I]IVFRU in vitro, only the 143B-LTK cells accumulated radioactivity. The acid-soluble fraction from 143B-LTK cell lysates contained 8-fold greater activity than the acid-insoluble fraction after an 8-h exposure to [(125)I]IVFRU. Biodistribution of [(125)I]IVFRU in nude mice bearing subcutaneous 143B and 143B-LTK tumors revealed widespread distribution of the nucleoside in vivo but with specific localization in 143B-LTK tumors. CONCLUSION: The underlying biochemical process of metabolic entrapment of IVFRU in human osteosarcoma cells expressing HSV-1 TK is responsible for selective localization in these cells. The differences in subcellular distribution into the nucleic acid fraction, and in cytotoxicity, reflect the importance of cell type and lineage as determinants of the performance of gene imaging radiopharmaceuticals.

Cytotoxicity and cellular uptake of pyrimidine nucleosides for imaging herpes simplex type-1 thymidine kinase (HSV-1 TK) expression in mammalian cells.

In vivo transfer of the herpes simplex virus type-1 thymidine kinase (HSV-1 TK) gene, with subsequent administration of antiviral drugs such as ganciclovir, has emerged as a promising gene therapy protocol for treating proliferative disorders. The in vitro cytotoxicities (IC(50)) for two series of 5-iodo- and (E)-5-(2-iodovinyl)-substituted 2'-deoxy- and 2'-deoxy-2'-fluoro-pyrimidine nucleosides ranged from millimolar to low nanomolar concentrations in mammalian tumor cell lines (KBALB; R-970-5; 143B; EMT-6) and their counterparts engineered to express HSV-1 TK (KBALB-STK; 143B-LTK). Their HSV-1 TK selectivity indices ranged from one (nonselective) to one million (highly selective) based on cytotoxicity, with FIRU being the least toxic to all cell lines, and FIAU being most toxic. HSV-1 TK selectivity, based on uptake, ranged from 10 to 140, with IVDU being most selective for HSV-1 TK expressing cells, followed by IVFRU, FIRU, FIAU, IVFAU and finally IUDR. Phosphorylation of [(125)I]FIAU led to incorporation of the radiolabel into nucleic acids, whereas IVFRU and FIRU radioactivity was trapped primarily in the nucleotide pool. These data indicate that cytotoxicity does not depend on initial metabolic trapping (e.g., phosphorylation), but on elaboration of the mononucleotides to more cytotoxic anabolites. Lipophilicities and nucleoside transport rates of the six nucleosides tested were within narrow ranges. This supports the premise that cellular biochemistry, and not cellular bioavailability, is responsible for the observed broad range of cytotoxicity and trapping. In vivo biodistribution studies with 5-[(125)I]iodo-2'-fluoro-2'-deoxyribouridine (FIRU), 5-[(125)I]iodo-2'-fluoro-2'-deoxyarabinouridine (FIAU) and (E)-5-(2-[(125)I]iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) demonstrate selective accumulation of all three radiotracers in HSV-1 TK-expressing KBABK-STK tumors, compared to their very low accumulation in the non-HSV-1 TK-expressing KBALB tumors, in Balb/c mice. In summary, these nucleosides are unpredictably cytotoxic to the various cell lines studied, and this unpredictability extends across the HSV-1 TK expression characteristic; their uptake by cells engineered to express HSV-1 TK is also dependent on the molecular construction of the gene cassette carrying the viral TK gene.

Uncertainty quantification and integration of machine learning techniques for predicting acid rock drainage chemistry: a probability bounds approach.

Acid rock drainage (ARD) is a major pollution problem globally that has adversely impacted the environment. Identification and quantification of uncertainties are integral parts of ARD assessment and risk mitigation, however previous studies on predicting ARD drainage chemistry have not fully addressed issues of uncertainties. In this study, artificial neural networks (ANN) and support vector machine (SVM) are used for the prediction of ARD drainage chemistry and their predictive uncertainties are quantified using probability bounds analysis. Furthermore, the predictions of ANN and SVM are integrated using four aggregation methods to improve their individual predictions. The results of this study showed that ANN performed better than SVM in enveloping the observed concentrations. In addition, integrating the prediction of ANN and SVM using the aggregation methods improved the predictions of individual techniques.

Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU.

Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives. The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy--D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy--D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of 123I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with 123I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). 123I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy--D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with 123I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after 123I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with the transgene in the former E1 region, driven by a modified CMV promoter, and a novel replication-competent vector with the HSV1-tk gene in E3 driven by the natural E3 promoter. The human glioma cell lines U87MG and T98G were infected with a multiplicity of infection (m.o.i.) of 10. Forty-eight hours later the cells were incubated with 123I-FIRU and radioactivity was measured in a gamma counter. We found significantly higher levels of radioactivity in both cell lines following infection with the replication-competent vector (P<0.001). NIH-bg-nu-xid mice were then inoculated subcutaneously with U87MG cells. Tumours (approximately 1,000 mm3) were injected with 108 and 109 Infectious Units (I.U.) of either vector. After 48 h, the tracer was injected, followed by gamma camera imaging and direct measurement of radioactivity in the tumours at 4 h p.i. Images and direct measurements indicated increased uptake of tracer with higher I.U. and also demonstrated increased accumulation of tracer in the tumours treated with the replication-competent adenoviral vector (P=0.03). These results demonstrate that 123I-FIRU in combination with HSV1-tk is a valuable tracer for in vivo monitoring of adenoviral gene transfer.