| 1. |
- Alakangas, Lena, et al.
(author)
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Project: Improve Resource Efficiency and Minimize Environmental Footprint
- 2016
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Other publication (pop. science, debate, etc.)abstract
- The REMinE project is organized in five work packages that comprise: detailedcharacterization and risk assessment of the mine wastes selected (WP2), identification of new processing methods for mine waste (WP3), characterization and risk assessment of the remaining residuals (WP4), outlining business opportunities and environmental impact in a conceptual model for sustainable mining (WP5). The project comprises case studies of historical mine wastes from three different European countries, namely Portugal, Romania and Sweden. The interdisciplinary research collaboration in this project is innovative in the sense that separation of minerals and extraction of metals not only are basedon technical and economic gain but also considers the environmental perspective.
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| 2. |
- Amare, Azmeraw, et al.
(author)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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In: Research square. - : Research Square Platform LLC.
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Journal article (peer-reviewed)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 3. |
- Amare, Azmeraw T, et al.
(author)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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In: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Journal article (peer-reviewed)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 4. |
- Amare, Azmeraw T, et al.
(author)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Journal article (peer-reviewed)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 5. |
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| 6. |
- Coombes, Brandon J, et al.
(author)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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In: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
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Journal article (peer-reviewed)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 7. |
- Herrera-Rivero, Marisol, et al.
(author)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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In: Research square.
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Other publication (other academic/artistic)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 8. |
- Herrera-Rivero, Marisol, et al.
(author)
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Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
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In: Research square.
-
Other publication (other academic/artistic)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
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| 9. |
- Holmberg, Anna, et al.
(author)
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General somatic health and lifestyle habits in individuals with obsessive- compulsive disorder : an international survey
- 2024
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In: BMC Psychiatry. - 1471-244X. ; 24:1
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Journal article (peer-reviewed)abstract
- Background: Obsessive-compulsive disorder (OCD) has been associated with a broad range of health-related issues. Unhealthy lifestyle habits such as physical inactivity, an unhealthy diet, smoking, and alcohol consumption are hypothesized to contribute to this association. However, the lifestyle habits of individuals with OCD have been scarcely investigated. In this international survey, we explored the physical health and lifestyle habits of adults with a self-reported diagnosis of OCD. Methods: An online global survey available in seven languages was disseminated through interest organizations and social media between July 2021 and March 2022. The survey included questions relating to socio-demographic variables and clinical characteristics (including OCD symptom severity – as measured with the 12-item self-report scale Obsessive-Compulsive Inventory [OCI-12] – and psychotropic medication), physical health, and lifestyle habits. Frequencies and percentages, or means and standard deviations, as appropriate, were calculated. Subgroup analyses by OCD symptom severity, gender, and age group were performed. Results: A total of 496 individuals with OCD completed the survey and were included in the analyses (mean age = 36.0 years, SD = 12.5, range 18–79; 78.8% women). Most participants were from Europe (n = 245, 49.4%) and North America (n = 187, 37.7%). OCD symptom severity scores were on the moderate range (OCI-12 mean score = 21.2, SD = 9.1). A majority (n = 354, 71.4%) reported having comorbid somatic health issues, mainly allergies, gastrointestinal conditions, and cardiometabolic conditions. Nearly half of the sample (n = 236, 47.6%) reported a body mass index ≥ 25, corresponding to at least overweight. A significant proportion of the participants reported low physical activity (n = 271, 55.0%), unhealthy dietary habits (n = 182, 36.7%), risk consumption of alcohol (n = 111, 22.3%), and non-restorative sleep (n = 268, 54.0%). Subgroup analyses showed overall similar results across groups, with some exceptions. Conclusions: In this sample, individuals with OCD self-reported a range of health-related issues and a number of unhealthy lifestyle behaviors, most prominently a lack of physical activity. Interventions aimed at modifying unhealthy lifestyles to prevent or improve health conditions beyond the psychiatric symptoms should be considered.
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| 10. |
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| 11. |
- Hou, Liping, et al.
(author)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 12. |
- Hällström, Lina, et al.
(author)
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Geochemical characterization of W, Cu and F skarn tailings at Yxsjöberg, Sweden
- 2018
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In: Journal of Geochemical Exploration. - : Elsevier. - 0375-6742 .- 1879-1689. ; 194, s. 266-279
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Journal article (peer-reviewed)abstract
- Little attention has been paid to tailings from skarn ore deposits and their environmental impact, even though they can contain elevated concentrations of elements of potential concern together with sulfides and fluorite. Historical skarn tailings at Yxsjöberg, Sweden, containing e.g. Be, Bi, Cu, F, Sn, S, W, and Zn were geochemically characterized as a first step to evaluate the environmental impact and the potential to re-mine the tailings. The tailings were deposited between 1897 and 1963 in the Smaltjärnen Repository without dams or a complete cover, and have been in contact with the atmosphere for >30 years. Four vertical cores throughout the tailings were taken and divided into 134 subsamples, which were analyzed for total concentrations and paste pH. Selected samples from different depths were mineralogically characterized using optical microscopy, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), Raman vibrational spectroscopy, and X-ray diffraction (XRD). Minerals, hand-picked from drilled rock cores, were analyzed for the element content, and a modified Element to Mineral Conversion (EMC) that pinpoints the quantitative distribution of elements between the minerals in the tailings was carried out. The average concentrations of Be, Bi, Cu, Sn, Zn, W, F and S in the tailings were 284, 495, 946, 559, 301, and 960 ppm, and 1.9 and 1.2 wt%, respectively. The tailings has reached a late stage development due to pyrrhotite oxidation resulting in low pH (<4) in the uppermost tailings, and formations of secondary minerals such as gypsum, hydrous ferric oxides (HFO) and orthogonal calcite. Secondary pyrite and magnetite, formed from monoclinic pyrrhotite was detected, and different weathering rates of secondary pyrite, hexagonal and monoclinic pyrrhotite was indicated, with secondary pyrite as the most stable and monoclinic pyrrhotite as the least. The rare and easily-weathered mineral danalite (Fe4Be3(SiO4)3S) was found in the drilled rock cores and by XRD in the tailings. However, the mineral could not be found by optical microscopy or SEM-EDS. This suggests that the mineral has been weathered to a great extent, which poses a high risk of releasing elements of potential concern to the groundwater since danalite contains approximately 40% of the total Be and Zn concentrations in the tailings. Fluorine was mainly found in fluorite, Cu in chalcopyrite, and Bi in bismuthinite; which all showed signs of weathering in acidic condition in the uppermost part, subsequent with decreased concentrations, followed by accumulation peaks deeper down in the tailings correlated with Al. Tungsten was mainly found in scheelite; most grains were unweathered, but a few grains had altered rims or HFO on the mineral surfaces. Tin was mainly found in ferrohornblende, hedenbergite and grossular. Beryllium, Cu, F, and Zn has high potential to be released to the surrounding environment from the Smaltjärnen Repository, while W, Bi and Sn are relatively stable in the tailings. Most of the scheelite is intact and re-mining could, therefore, be a suitable remediation method that would both reduce the environmental impact and simultaneously support the supply of critical raw materials in the EU.
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| 13. |
- Hällström, Lina, et al.
(author)
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Metal Release from Acidic and Near-Neutral pH-Conditions in Historical W, Cu and F Skarn Tailings at Yxsjöberg, Sweden
- 2018
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In: 11th ICARD | IMWA | WISA MWD 2018 Conference. - 9780620806503 ; , s. 351-356
-
Conference paper (peer-reviewed)abstract
- Weathering products stored in the pore water and/or as easily soluble salts in historical skarn tailings containing Be, Bi, Cu, W, and Zn, were released in water soluble fraction in the upper-most acidic tailings, at the visual oxidation front (1.5m), and/or below 2.5m (pH>7). Thus, there is a risk that these metals can pollute receiving waters by neutral mine drainage. Re-mining the tailings could be a suitable remediation method that would both reduce the environmental impact and simultaneously support the supply of metals.
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| 14. |
- Hällström, Lina, P.B
(author)
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Geochemical Characterization of Historical W, Cu and F Skarn Tailings at Yxsjöberg, Sweden : With focus on scheelite weathering and tungsten (W) mobility
- 2018
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Licentiate thesis (other academic/artistic)abstract
- Little attention has been paid to tailings from skarn ore deposits and their environmental impact, even though they can contain elevated content of elements of potential concern. Historical skarn tailings from a former scheelite mine at Yxsjöberg, Sweden, containing e.g. Be, Bi, Cu, F, Sn, S, W, and Zn were geochemically characterized as a first step to evaluate the potential environmental impact and if re-mining of the tailings can be a remediation option. Beryllium, Bi, F, and W are considered as elements of potential concern, and are at the same time listed by the European Commission (2017) as critical raw materials. Scheelite is considered as a relatively stable mineral but most research has been focused on extraction processes. A few laboratory studies have shown weathering of scheelite by artificial groundwater, where the release of WO42-was hypothesized to be due to anion exchange by CO32-. Thus, the release of W from scheelite should be favorable in skarn tailings due to the presence of carbonates.The tailings at Yxsjöberg were deposited between 1897 and 1963 in the Smaltjärnen Repository without dams or a complete cover, and have been in contact with the atmosphere for more than 30 years. Four vertical cores (P2, P4, P5, and P7) throughout the tailings were taken and divided into 134 subsamples, and analyzed for their total chemical composition and paste pH. Selected samples from different depths were mineralogically characterized using optical microscopy, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), Raman vibrational spectroscopy, and X-ray diffraction (XRD). Minerals, hand-picked from drilled rock cores, were analyzed for the element content, and a modified Element to Mineral Conversion (EMC) in combination with a 7-step sequential extraction of the tailings was used to pinpoint the quantitative distribution of elements between the minerals in the tailings. Scheelite weathering and secondary sequestration of W was studied in detail in one representative core. The release of elements to groundwater in the tailings and downstream surface water was measured monthly during 2018 to especially examine the mobility of W.The average concentrations of Be, Bi, Cu, Sn, Zn, W, F and S in the tailings were 280, 490, 950, 560, 300, and 960 ppm, and 1.9 and 1.2 wt.%, respectively. The uppermost tailings have been exposed to the atmosphere for more 30 years, with intensive pyrrhotite oxidation and carbonate dissolution, resulting in low pH (<4) condition, release of elements, and subsequent formations of secondary minerals such as gypsum and hydrous ferric oxides (HFO). Two different deposition periods were identified in one vertical profile. The later period of deposition extended from the ground surface down to 3.5 m, and the older from 3.6 to 6 m. Both periods had unoxidized tailings in the bottom and oxidized sulfides, depletion of calcite and HFO formations upwards.Tungsten was primarily found in scheelite and the abundance was 0.1 wt.% in the tailings at Yxsjöberg. Accumulation peaks of W were found with depth in P2, P4 and P7. In the upper peak of P4, 30% of the total W was associated with secondary HFO. This indicates that weathering of scheelite and secondary capturing of W had occurred in the tailings. At present time, a peak of W in water soluble phases where coinciding with accumulated C in the solid phase at 2.5m depth. Carbonate ions were released when calcite was neutralizing the acid produced in the upper oxidized tailings and the released CO32-was transported downwards to conditions with pH >7. There, it mainly had precipitated as secondary calcite, but small parts are hypothesized to have exchanged WO42-on the surface of scheelite,releasing WO42-to the pore water. In the oxidized tailings of the older and deeper tailing,goethite was found as rims around scheelite grains. This is probably due to Fe ions attracted to the negative surface of scheelite. This is suggested to decrease further weathering of scheelite, and also to some extent decrease the release of WO42-to the groundwater from above lying layers through adsorption.The changes in geochemical conditions in the tailings have decreased the water quality in receiving waters of Smaltjärnens Repository with increased concentrations of Ca, F, Fe,Mn, and SO42-. pH was on average 6.3 in the groundwater in the tailings and 5.7 in the surface water 300 m downstream. EC was on average 2.6 mS/cm in the groundwater and 131 μS/cm in the surface water. Low concentrations of dissolved W was found in the groundwater (max: 20 μg/l) in the tailings and in the downstream surface water the W concentration (max: 0.2 μg/l) was 20 times larger than the reference sample. These results show that scheelite is releasing W to a limited degree to downstream waters and are therefore a potential resource to re-mine to support the supply of critical raw materials in the EU.Beryllium, F, and Zn were released to the downstream surface water from the Smaltjärnen Repository, and to a higher degree than W. The rare and easily-weathered mineral danalite (Fe4Be3(SiO4)3S) contained approximately 40% of the total Be and Zn concentrations in the tailings and is suggested to be the major source to the release of Be and Zn. Fluorine was mainly found in fluorite which showed signs of weathering in the acidic condition in the uppermost oxidized tailings, subsequent with decreased content in the tailings. The mobility of these elements will be further studied.
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| 15. |
- Hällström, Lina P.B., et al.
(author)
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The geochemical behaviour of Be and F in historical mine tailings of Yxsjöberg, Sweden
- 2020
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In: Journal of Geochemical Exploration. - : Elsevier. - 0375-6742 .- 1879-1689. ; 218
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Journal article (peer-reviewed)abstract
- The speciation, mobility, transport, and fate of beryllium (Be) in the terrestrial environment is poorly studied even though it is considered to be one of the most hazardous elements in the periodic table. Historical tailings containing the unusual mineral danalite [Be3(Fe4.4Mn0.95Zn0.4)(SiO4)3.2S1.4] together with Fe-sulfides and fluorite has been stored open to the atmosphere for more than 50y. Environmental mineralogy, which combines geochemical and mineralogical techniques, was used to elucidate the weathering of danalite and fluorite. Danalite is unstable in oxic conditions due to the occurrence of Fe(II) and S-(II) in the crystal lattice and has oxidized at the same pace as pyrrhotite in the tailings. The acidic conditions generated from sulfide oxidation and the release of F from fluorite weathering have most likely enhanced Be mobility in the tailings. Secondary gypsum, hydrous ferric oxides and Al-oxyhydroxides are hypothesized to have played an important role regarding the mobility of Be in the tailings. The results indicate that Be released from danalite was first scavenged by these secondary minerals through co-precipitation. However, the dissolution of secondary gypsum due to changing geochemical conditions has also released Be to the groundwater. The groundwater at the shore of the tailings revealed the highest Be concentrations measured anywhere in the world (average: 4.5 mg/L) even though the water has a circumneutral pH. This extraordinary finding can be explained by high concentrations of F (73 mg/L), as F and Be have been shown to form strong complexes. The weathering of danalite and fluorite will continue for hundreds of years if remediation measures are not taken. Re-mining the tailings could be an appropriate remediation method.
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| 16. |
- Hällström, Lina, et al.
(author)
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Scheelite weathering and tungsten (W) mobility in historical oxidic-sulfidic skarn tailings at Yxsjöberg, Sweden
- 2020
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In: Environmental Science and Pollution Research. - : Springer. - 0944-1344 .- 1614-7499. ; 27:6, s. 6180-6192
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Journal article (peer-reviewed)abstract
- More knowledge of the geochemical behavior of tungsten (W) and associated contamination risks is needed. Therefore, weathering of scheelite (CaWO4) and secondary sequestration and transport of W to groundwater in historical skarn tailings and surface water downstream of the tailings were studied. The tailings contained 920 mg/kg W, primarily in scheelite. Mineralogical and geochemical analyses were combined to elucidate the geochemical behavior of W in the tailings, and water samples were taken monthly during 2018 to monitor its mobility. In the tailings, a large peak of W was found at 1.5 m depth. There, 30 wt%. of W was present in easily reducible phases, indicating former scheelite weathering. Currently, W is being released from scheelite to water-soluble phases at 2.5 m depth. The release of WO42− is hypothetically attributed to anion exchange with CO32− released from calcite neutralizing acid produced from pyrrhotite oxidation in the upper tailings and transported downwards to pH conditions > 7. Higher concentrations of dissolved W were found in the groundwater and particulate W in downstream surface water than in reference water, but they were lower than current contamination thresholds. Tungsten showed correlations with hydrous ferric oxides (HFO) in both the tailings and surface water.
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| 17. |
- Hällström, Lina
(author)
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Source, mobility and fate of critical Be, Bi, F and W from historical sulfidic-oxidic skarn tailings : Re-mining as remediation method?
- 2021
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Doctoral thesis (other academic/artistic)abstract
- There is a potential risk that geochemical cycles of several critical metals will be affected in the pristine environment, when mining of these metals increases to meet the demand in green technology. The identification of critical metals is based on the economic importance and vulnerability to supply restrictions. In the past, naturally low concentrations in the environment, and instrumental analysis with higher detection limits, has limited research regarding several of these critical metals. However, to understand their geochemical behavior and potential environmental impact are of high importance to ensure a responsible development of mine waste- and water management. Skarn ores can contain high amounts of Fe-sulfides, carbonates and fluorite, together with enriched concentrations of critical metals such as Be, Bi and W. Nevertheless, little attention has been paid to mine drainage from skarn tailings and their environmental impact, compared to tailings from sulfidic deposits. At Yxsjö mine site, Sweden, skarn tailings enriched in the major elements C, F, S (1.0, 1.9 and 1.2 wt.%.) and Be, Bi, and W (average 280, 500 and 960 ppm, respectively) were deposited in Smaltjärnen repository (1918-1963). The tailings were stored in ambient conditions until 1993 when the tailings were covered by sewage sludge. In-between 1969-1989, tailings were discharged into Morkulltjärnen repository, which was covered with sewage sludge and partly water saturated directly after closure. This thesis focuses on the Smaltjärnen tailings. The element distribution in the tailings were identified by combining 1) total concentrations of nine targeted minerals from rock drilled cores, 2) total concentrations of 99 samples from four intact tailings cores, and 3) environmental mineralogy (EM) conducted on one of the cores. The environmental mineralogy included paste-pH, sequential extractions, optical microscopy, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), Raman vibrational spectroscopy and X-ray diffraction (XRD). Environmental mineralogy was also used to reveal geochemical processes affecting the mobility of elements in the tailings. Monthly water samples (May-October, 2018) were taken in three groundwater wells in the tailings, and at five surface water locations downstream the tailings. At three surface water locations, the diatom taxonomy response to the water quality was used to evaluate the impact on ecosystems. The quality of the mine drainage was compared to surface water downstream Morkulltjärnens repository and to a reference point. The overall results were used to evaluate the need for remediation, and particularly, the possibility to use re-mining as remediation method. The Smaltjärnen tailings contained 88 wt.%. of Ca-rich silicates accompanied by minerals such as calcite [CaCO3], fluorite [CaF2], monoclinic and hexagonal pyrrhotite [Fe1-xS)], danalite [Be3(Fe4.4Mn0.95Zn0.4)(SiO4)3.2S1.4], scheelite [CaWO4] and bismuthinite [Bi3S2] (average 5.7, 3.6, 2.4, 0.3, 0.1 wt.%. and 0.1 wt.%., respectively). Both pyrrhotite and danalite had oxidized in the upper parts of the tailings down to 2.5m depth, and calcite had partly neutralized the acid produced resulting in a pH decrease from 8 to 4 in the upper parts of the tailings. Weathering of danalite was intensified by the more acidic conditions (pH<6), in which Be hydrolyzes. The lowered pH enabled dissolution of fluorite, resulting in severely high concentrations of F in the groundwater (average 73 mg/L) and surface water (average 1.6 mg/L). In the uppermost tailings, secondary gypsum [CaSO4], Al-complexes and hydrous ferric oxides (HFO) had formed. The geochemical behavior of Be was complex in the tailings and in surface water downstream the tailings. According to the sequential extraction, Be released from danalite in the upper most tailings were present in water soluble phases, as exchangeable phases and had co-precipitated with Al- and Fe-oxyhydroxides. A strong correlation between Be, Ca and S in water soluble phases and in the surface water downstream the tailings indicated that Be partly substituted for Ca in secondary gypsum. In two groundwater wells, secondary precipitates of a white sludge containing Be, Al, F and Zn were found, indicating that Be was partly removed from the groundwater by Al-complexes. In the third groundwater well, the globally highest dissolved concentrations of Be were measured (average 4.5 mg/L), and in the surface water the concentrations (average 41 µg/L) were well above thresholds values for aquatic organisms (1 µg/L). In these pH-conditions (average 5.7-6.5) and oxygenated waters, Be is expected to precipitate as Be(OH)2 if complexing ligands are absent. A strong correlation between dissolved Be and F was found in the surface water, indicating that Be-fluorocomplexes had formed. Bismuth and W have previously been considered as relatively immobile elements. However, the results showed that both Bi and W had partly been mobilized from their primary minerals (bismuthinite and scheelite) in the tailings. Weathered bismuthinite and scheelite grains with rims of goethite and water soluble phases of Bi and W were found in the deeper tailings with pH>7. The release of WO42- was hypothetically attributed to anion exchange with CO32- on surfaces of scheelite. Because, at the same depth where W was mobilized, solid C was accumulated and secondary orthogonal calcite was frequently detected with Raman spectroscopy. Bismuth was scavenged in the tailings by exchangeable phases and co-precipitation with HFO in the upper-most tailings. In the groundwater, Bi was just above the detection limit in all groundwater wells, while W was found in elevated concentrations. In the surface water, Bi and W were transported in the particulate phase together with Fe, and settled in the sediments a few 100 meters from the tailings outlet. Surface water downstream Morkulltjärnen had a near-neutral pH (average 6.6) and of all elements analyzed, only dissolved W (average 1.1 µg/L) were high compared to threshold values (0.8 µg/L) and the reference sample. Dissolved Be, Ca, F and S from Smaltjärnen, and dissolved W from Morkulltjärnen were found in elevated concentrations more than 2 km from the mine site. Along this distance, metal tolerant diatom species (Achnanthidium minutissimum group II and Brachysira neoexilis, respectively) were dominant (>50%), indicating a negative impact on ecosystems. The mine drainage from Smaltjärnen had a larger negative impact on the diatom taxonomy with higher abundance of metal tolerant species, lower richness and evenness, more than 1% of deformed valves and the taxonomy was affected by the lower pH, compared to diatoms downstream Morkulltjärnen repository. In conclusion, pyrrhotite oxidation was the direct or indirect cause of Be, Bi, F and W mobilization in the Smaltjärnen tailings, resulting in low quality mine drainage. The oxidation rate decrease with time, but weathering of the Smaltjärnen tailings is expected to be ongoing for hundreds of years since only a small part had weathered during the 50-100 years of storage. The low water quality and negative impact on diatoms, stress the need for remediation. Low concentrations of Be, Bi, Ca, F, Fe and S, accompanied by a near-neutral pH (average pH 6.6) downstream Morkulltjärnen, suggested that cover and water saturation could inhibit sulfide and danalite oxidation, and indirectly prevent fluorite weathering. However, high concentrations of dissolved W downstream Morkulltjärnen displayed that cover and water saturation can increase the mobility of W in the Smaltjärnen tailings, which needs to be taken into consideration. This thesis shows the importance of understanding the complex mineral and element matrix in skarn tailings before choosing remediation technique. Re-mining could be a beneficial remediation method since most W were found in intact scheelite grains. However, more research regarding the mineral processing and metallurgy is needed to ensure a sustainable extraction technique that separates sulfides, carbonates, danalite and fluorite, and deposits them in a proper way.
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| 18. |
- Kalman, Janos L, et al.
(author)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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In: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 19. |
- Kelsoe, John, et al.
(author)
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Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
- 2023
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In: Research square.
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Other publication (other academic/artistic)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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| 20. |
- Lindahl, Bertil, et al.
(author)
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An algorithm for rule-in and rule-out of acute myocardial infarction using a novel troponin I assay
- 2017
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:2, s. 125-131
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Journal article (peer-reviewed)abstract
- Objective To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay. Methods The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers. Results In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts. Conclusions This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.
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| 21. |
- Ljung, Lina, et al.
(author)
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A Rule-Out Strategy Based on High-Sensitivity Troponin and HEART Score Reduces Hospital Admissions
- 2019
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In: Annals of Emergency Medicine. - : MOSBY-ELSEVIER. - 0196-0644 .- 1097-6760. ; 73:5, s. 491-499
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Journal article (peer-reviewed)abstract
- Study objective: We evaluate whether a combination of a 1-hour high-sensitivity cardiac troponin algorithm and History, ECG, Age, Risk Factors, and Troponin (HEART) score reduces admission rate (primary outcome) and affects time to discharge, health care-related costs, and 30-day outcome (secondary outcomes) in patients with symptoms suggestive of an acute coronary syndrome.Methods: This prospective observational multicenter study was conducted before (2013 to 2014) and after (2015 to 2016) implementation of a strategy including level of high-sensitivity cardiac troponin T or I at 0 and 1 hour, combined with the HEART score. Patients with a nonelevated baseline high-sensitivity cardiac troponin level, a 1-hour change in high-sensitivity cardiac troponin T level less than 3 ng/L, or high-sensitivity cardiac troponin I level less than 6 ng/L and a HEART score less than or equal to 3 were considered to be ruled out of having acute coronary syndrome. A logistic regression analysis was performed to adjust for differences in baseline characteristics.Results: A total of 1,233 patients were included at 6 centers. There were no differences in regard to median age (64 versus 63 years) and proportion of men (57% versus 54%) between the periods. After introduction of the new strategy, the admission rate decreased from 59% to 33% (risk ratio 0.55 [95% confidence interval {CI} 0.48 to 0.63]; odds ratio 0.33 [95% CI 0.26 to 0.42]; adjusted odds ratio 0.33 [95% CI 0.25 to 0.42]). The median hospital stay was reduced from 23.2 to 4.7 hours (95% CI of difference -20.4 to -11.4); median health care-related costs, from $1,748 to $1,079 (95% CI of difference -$953 to -$391). The number of clinical events was very low.Conclusion: In this before-after study, clinical implementation of a 1-hour high-sensitivity cardiac troponin algorithm combined with the HEART score was associated with a reduction in admission rate and health care burden, with very low rates of adverse clinical events.
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| 22. |
- Ljung, Lina, et al.
(author)
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Sensitivity of undetectable level of high-sensitivity troponin T at presentation in a large non-ST-segment elevation myocardial infarction cohort of early presenters
- 2019
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 284, s. 6-11
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Journal article (peer-reviewed)abstract
- BACKGROUND: We aimed to evaluate the diagnostic sensitivity for myocardial infarction (MI) when using an undetectable level of high-sensitivity cardiac troponin T (hs-cTnT < 5 ng/L) at presentation combined with a non-ischemic electrocardiogram (ECG), to rule out MI in a non-ST-segment elevation MI (NSTEMI) cohort presenting ≤2 h from symptom onset. We also aimed to compare baseline characteristics and 30-day outcome in NSTEMI patients presenting with and without hs-cTnT < 5 ng/L.METHODS: All patients admitted to five centers in Sweden 2011-2015, after the introduction of hs-cTnT, who presented ≤2 h from symptom onset and received a final diagnosis of NSTEMI, were identified through the SWEDEHEART registry. These data and data of hs-cTnT levels were verified in the hospitals' medical records. The registry provided baseline and outcome data.RESULTS: Twenty-four (2.6%) of 911 NSTEMI patients presented with hs-cTnT < 5 ng/L. In patients presenting >1-≤2 h from symptom onset the sensitivity for MI when combining hs-cTnT and ECG was 99.4% (95% CI 98.4%-99.8%). In patients presenting ≤1 h, and in patients aged ≤65 years without prior MI, the sensitivity was insufficient. NSTEMI patients presenting with hs-cTnT < 5 ng/L were younger and had less often a prior MI. A total of 62.5 vs. 63.5% of the NSTEMI patients presenting with and without hs-cTnT < 5 ng/L underwent revascularization within 30 days and 4.5 and 3.2% died respectively.CONCLUSIONS: Hs-cTnT < 5 ng/L at presentation combined with a non-ischemic ECG may be used to rule out MI in patients presenting as early as >1 h from symptom onset with a sufficient sensitivity.
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| 23. |
- Löfmark, Henrik, et al.
(author)
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HEART-score can be simplified without loss of discriminatory power in patients with chest pain : Introducing the HET-score
- 2023
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In: American Journal of Emergency Medicine. - : Elsevier. - 0735-6757 .- 1532-8171. ; 74, s. 104-111
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Journal article (peer-reviewed)abstract
- BackgroundThe History, Electrocardiogram (ECG), Age, Risk factors and Troponin, (HEART) score is useful for early risk stratification in chest pain patients. The aim was to validate previous findings that a simplified score using history, ECG and troponin (HET-score) has similar ability to stratify risk.MethodsPatients presenting with chest pain with duration of ≥10 min and an onset of last episode ≤12 h but without ST-segment elevation on ECG at 6 emergency departments were eligible for inclusion. The HEART-score and the simplified HET-score were calculated. The endpoint was a composite of myocardial infarction (MI) as index diagnosis, readmission due to new MI or death within 30 days.ResultsHEART-score identified 32% as low risk (0-2p), 47% as intermediate risk (3-5p), and 20% as high risk (6-10p) patients. The endpoint occurred in 0.5%, 7.3% and 35.7%, respectively. HET-score identified 39%, 42% and 19% as low- (0p), intermediate- (1-2p) and high-risk (3-6p) patients, with the endpoint occurring in 0.6%, 6.2% and 43.2%, respectively.When all variables included in the HEART-score were included in a multivariable logistic regression analysis, only History (OR, CI [95%]): 2.97(2.16–4.09), ECG (1.61[1.14–2.28]) and troponin level (5.21[3.91–6.95]) were significantly associated with cardiovascular events. When HEART- and HET-score were compared in a ROC-analysis, HET-score had a significantly larger AUC (0.887 vs 0.853, p < 0.001).ConclusionsCompared with HEART-score, HET-score is simpler and appears to have similar ability to discriminate between chest pain patients with and without cardiovascular event.
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| 24. |
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| 25. |
- Martinsson, Lina
(author)
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Biology of lithium response in bipolar disorder : genetic mechanisms and telomeres
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Background: Bipolar disorder is a common, chronic and severe mental illness, causing suffering and large costs. Lithium treatment is the golden standard and works in 2/3 of patients, of which 50% are called lithium responders. There is strong evidence that both bipolar disorder and the degree of lithium response are highly heritable, although many mechanisms are unknown. Short telomere length has been found in both somatic and psychiatric disorders, but little is known about telomeres in bipolar disorder and nothing about telomeres and lithium treatment. A few studies limited in size have reported an increased risk of kidney cancer in lithium-treated patients. These findings have led to warnings and changes in policies for lithium treatment, although clinicians and researchers have disputed it. There is thus a clinical need for large-scale studies and reliable evaluations of the cancer incidence in lithium-treated bipolar patients. Aims: The overall aim of this thesis is to increase the knowledge of the genetic mechanisms in bipolar disorder and in lithium response. Specifically, it aims to find genetic associations to lithium response and to investigate how telomere length is related to bipolar disorder and lithium treatment. Additionally, it explores the overall and site-specific cancer incidence in bipolar disorder and lithium treatment. Methods: Study I is a GWAS of lithium response. Study II is a retrospective study of telomere length in lithium-treated bipolar patients. Study III is an association study of a genetic variant in the hTERT gene (previously associated with short telomeres) and depression, and a retrospective cohort study of telomere length in depression. Study IV is a longitudinal study of telomere length in lithium-treated bipolar patients. Study V is a register study of overall and specific cancer incidence in lithium-treated bipolar patients compared to the general population. Results: I) A single locus with four linked common gene variants on chromosome 21 coding for long, non-coding RNAs, which might be important for brain gene regulation, was associated with lithium response. II) Leukocyte telomeres were 35% longer in bipolar patients compared to healthy controls and correlated positively with length of lithium treatment in patients who had had lithium for more than 2.5 years. Lithium responders had 10% longer telomeres than non-responders. Short telomeres were associated with a larger number of depressive episodes. III) A genetic variant in the hTERT gene was associated with the number of depressions in bipolar type 1 patients responding to lithium and with unipolar depression. Telomere length was shorter in depressed patients without previous childhood trauma. IV) The total reduction of leukocyte telomere length between tests was, for bipolar patients, an average of 2.1% per year versus 3.7% per year in healthy controls. Age at baseline had a positive effect while total time on lithium between tests had a negative effect on the leukocyte telomere length reduction independent of other confounders. In bipolar patients there was no association between the total number of leukocytes or leukocyte subtypes and leukocyte telomere length at follow-up. V) There was no increase in the overall or site-specific cancer incidence in lithium-treated patients in the age span of 50-84 years (N=2 393) compared to the general population (N=2 593 011). Conclusions: Association of lithium response to a genomic region containing long, noncoding RNA with potential importance for gene regulation in the brain adds a new piece of knowledge to the heritability of lithium response in bipolar disorder. Results must be replicated and translated into a biological context. The new finding of a decelerating effect of lithium treatment on telomere shortening suggests that lithium might have operative effects on telomere biology, which also has potential importance for lithium response and should be investigated further. An important clinical implication of the lack of difference in cancer incidence between lithium-treated bipolar patients and the general population is that recently added warnings for renal cancer in patients with long-term lithium treatment is unnecessary and ought to be omitted from the current policies.
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