| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Reinbold, C. S., et al.
(författare)
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Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder
- 2018
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
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| 3. |
- Scott, J., et al.
(författare)
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Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative
- 2019
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Ingår i: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.
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| 4. |
- Payler, S.J., et al.
(författare)
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Planetary science and exploration in the deep subsurface : results from the MINAR Program, Boulby Mine, UK
- 2017
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Ingår i: International Journal of Astrobiology. - : Cambridge University Press. - 1473-5504 .- 1475-3006. ; 16:2, s. 114-129
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Tidskriftsartikel (refereegranskat)abstract
- The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining. Copyright © Cambridge University Press 2016
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| 5. |
- Brack, W., et al.
(författare)
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Strengthen the European collaborative environmental research to meet European policy goals for achieving a sustainable, non-toxic environment
- 2019
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Ingår i: Environmental Sciences Europe. - : Springer Science and Business Media LLC. - 2190-4707 .- 2190-4715. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- To meet the United Nations (UN) sustainable development goals and the European Union (EU) strategy for a non-toxic environment, water resources and ecosystems management require cost-efficient solutions for prevailing complex contamination and multiple stressor exposures. For the protection of water resources under global change conditions, specific research needs for prediction, monitoring, assessment and abatement of multiple stressors emerge with respect to maintaining human needs, biodiversity, and ecosystem services. Collaborative European research seems an ideal instrument to mobilize the required transdisciplinary scientific support and tackle the large-scale dimension and develop options required for implementation of European policies. Calls for research on minimizing society's chemical footprints in the water-food-energy-security nexus are required. European research should be complemented with targeted national scientific funding to address specific transformation pathways and support the evaluation, demonstration and implementation of novel approaches on regional scales. The foreseeable pressure developments due to demographic, economic and climate changes require solution-oriented thinking, focusing on the assessment of sustainable abatement options and transformation pathways rather than on status evaluation. Stakeholder involvement is a key success factor in collaborative projects as it allows capturing added value, to address other levels of complexity, and find smarter solutions by synthesizing scientific evidence, integrating governance issues, and addressing transition pathways. This increases the chances of closing the value chain by implementing novel solutions. For the water quality topic, the interacting European collaborative projects SOLUTIONS, MARS and GLOBAQUA and the NORMAN network provide best practice examples for successful applied collaborative research including multi-stakeholder involvement. They provided innovative conceptual, modelling and instrumental options for future monitoring and management of chemical mixtures and multiple stressors in European water resources. Advancement of EU water framework directive-related policies has therefore become an option. Bt Aachen Biol, Aachen, Germany.
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| 6. |
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| 7. |
- Wallen, K. E., et al.
(författare)
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Integrating team science into interdisciplinary graduate education : an exploration of the SESYNC Graduate Pursuit
- 2019
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Ingår i: Journal of Environmental Studies and Sciences. - : Springer Science and Business Media LLC. - 2190-6483 .- 2190-6491. ; 9:2, s. 218-233
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Tidskriftsartikel (refereegranskat)abstract
- Complex socio-environmental challenges require interdisciplinary, team-based research capacity. Graduate students are fundamental to building such capacity, yet formal opportunities for graduate students to develop these capacities and skills are uncommon. This paper presents an assessment of the Graduate Pursuit (GP) program, a formal interdisciplinary team science graduate research and training program administered by the National Socio-Environmental Synthesis Center (SESYNC). Quantitative and qualitative assessment of the program’s first cohort revealed that participants became significantly more comfortable with interdisciplinary research and team science approaches, increased their capacity to work across disciplines, and were enabled to produce tangible research outcomes. Qualitative analysis of four themes—(1) discipline, specialization, and shared purpose, (2) interpersonal skills and personality, (3) communication and teamwork, and (4) perceived costs and benefits—encompass participants’ positive and negative experiences and support findings from past assessments. The findings also identify challenges and benefits related to individual personality traits and team personality orientation, the importance of perceiving a sense of autonomy and independence, and the benefit of graduate training programs independent of the university and graduate program environment.
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| 8. |
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| 9. |
- Helsen, Kenny, et al.
(författare)
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Impact of an invasive alien plant on litter decomposition along a latitudinal gradient
- 2018
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Ingår i: Ecosphere. - : Wiley. - 2150-8925 .- 2150-8925. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Invasive alien plant effects on ecosystem functions are often difficult to predict across environmental gradients due to the context-dependent interactions between the invader and the recipient communities. Adopting a functional trait-based framework could provide more mechanistic predictions for invasive species' impacts. In this study, we contrast litter decomposition rates among communities with and without the invasive plant Impatiens glandulifera in five regions along a 1600 km long latitudinal gradient in Europe. Across this gradient, four functional traits, namely leaf dry matter content (LDMC), specific leaf area (SLA), stem-specific density (SSD), and plant height, are correlated to rates of litter decomposition of standardized rooibos (labile), green tea (recalcitrant), and I. glandulifera litter. Our results show that both invaded and non-invaded plant communities had a higher expression of acquisitive traits (low LDMC and SSD, high SLA) with increasing temperature along the latitudinal gradient, partly explaining the variation in decomposition rates along the gradient. At the same time, invasion shifted community trait composition toward more acquisitive traits across the latitudinal gradient. These trait changes partly explained the increased litter decomposition rates of the labile litter fraction of rooibos and I. glandulifera litter in invaded communities, a shift that was most evident in the warmer study regions. Plant available nitrogen was lower in invaded communities, likely due to high nutrient uptake by I. glandulifera. Meanwhile, the coldest study region was characterized by a reversed effect of invasion on decomposition rates. Here, community traits related to low litter quality and potential allelopathic effects of the invader resulted in reduced litter decomposition rates, suggesting a threshold temperature at which invader effects on litter decomposition turn positive. This study therefore illustrates how functional trait changes toward acquisitive traits can help explain invader-induced changes in ecosystem functions such as increased litter decomposition.
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| 10. |
- Kademoglou, Katerina, et al.
(författare)
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In Vitro Inhalation Bioaccessibility of Phthalate Esters and Alternative Plasticizers Present in Indoor Dust Using Artificial Lung Fluids
- 2018
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Ingår i: Environmental Science and Technology Letters. - : American Chemical Society (ACS). - 2328-8930. ; 5:6, s. 329-334
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Tidskriftsartikel (refereegranskat)abstract
- Phthalate esters (PEs) are used as plasticizers in consumer products. Their low migration stability has resulted in the classification of PEs as major indoor contaminants. Because of PE's ubiquity and adverse health effects on humans and especially children, non-phthalate alternative plasticizers have been introduced into the market. This is the first study of in vitro inhalation bioaccessibility of PEs (e.g., DMP, DEP, and DEHP) and alternative plasticizers (e.g., DEHT and DINCH) via indoor dust to assess inhalation as an alternative route of exposure. Two artificial lung fluids were used, mimicking two distinctively different pulmonary environments: (1) artificial lysosomal fluid (ALF, pH 4.5) representing the intracellular acidic lung fluid inhaled particle contact after phagocytosis by alveolar macrophages and (2) Gamble's solution (pH 7.4), the extracellular healthy fluid for deep lung deposition of dust. DMP and DEP were highly bioaccessible (>75%), whereas highly hydrophobic compounds such as DEHP, DINCH, and DEHT were <5% bioaccessible via both artificial lung fluids. Our findings show that the inhalation bioaccessibility of PEs is primarily governed by their hydrophobicity and water solubility. Further research is necessary to develop unified and biologically relevant inhalation bioaccessibility tests, employed as part of human risk assessment of volatile and semivolatile organic pollutants.
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