| 1. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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- Glasbey, JC, et al.
(author)
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- 2021
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- Wheeler, Eleanor, et al.
(author)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Journal article (peer-reviewed)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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| 12. |
- AghaKouchak, Amir, et al.
(author)
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Anthropogenic Drought : Definition, Challenges, and Opportunities
- 2021
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In: Reviews of geophysics. - : John Wiley & Sons. - 8755-1209 .- 1944-9208. ; 59:2
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Research review (peer-reviewed)abstract
- Traditional, mainstream definitions of drought describe it as deficit in water-related variables or water-dependent activities (e.g., precipitation, soil moisture, surface and groundwater storage, and irrigation) due to natural variabilities that are out of the control of local decision-makers. Here, we argue that within coupled human-water systems, drought must be defined and understood as a process as opposed to a product to help better frame and describe the complex and interrelated dynamics of both natural and human-induced changes that define anthropogenic drought as a compound multidimensional and multiscale phenomenon, governed by the combination of natural water variability, climate change, human decisions and activities, and altered micro-climate conditions due to changes in land and water management. This definition considers the full spectrum of dynamic feedbacks and processes (e.g., land-atmosphere interactions and water and energy balance) within human-nature systems that drive the development of anthropogenic drought. This process magnifies the water supply demand gap and can lead to water bankruptcy, which will become more rampant around the globe in the coming decades due to continuously growing water demands under compounding effects of climate change and global environmental degradation. This challenge has de facto implications for both short-term and long-term water resources planning and management, water governance, and policymaking. Herein, after a brief overview of the anthropogenic drought concept and its examples, we discuss existing research gaps and opportunities for better understanding, modeling, and management of this phenomenon.
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| 13. |
- Annosi, Maria Carmela, et al.
(author)
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An Ambidextrous Approach to Practice-Based Innovation for Social Product Development : Lessons from A Dutch Company
- 2022
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In: IEEE transactions on engineering management. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9391 .- 1558-0040. ; 69:2, s. 376-387
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Journal article (peer-reviewed)abstract
- In the face of increasing competition, an organization's capacity to acquire knowledge from the outside has become fundamental for new product development. Pertinent extant literature has stressed how an organization should practice social product development, allowing for the inclusion of all types of stakeholders in idea generation, selection, validation, and commercialization. This article investigates how organizations can acquire, maintain, and use different sources of knowledge via ambidextrous habits of exploitation and exploration to sustain social product development. A case study based on 27 semistructured interviews and field observations at a leading, large-size, Dutch food-service company has been carried out. The findings illustrate the organizational processes and mechanisms that the company has adopted to address and combine practice- A nd research-based knowledge, as well as the main barriers limiting the accumulation and usage of this knowledge inside organizational boundaries.
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| 14. |
- Harris, Ted D., et al.
(author)
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What makes a cyanobacterial bloom disappear? : A review of the abiotic and biotic cyanobacterial bloom loss factors
- 2024
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In: Harmful Algae. - : Elsevier. - 1568-9883 .- 1878-1470. ; 133
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Research review (peer-reviewed)abstract
- Cyanobacterial blooms present substantial challenges to managers and threaten ecological and public health. Although the majority of cyanobacterial bloom research and management focuses on factors that control bloom initiation, duration, toxicity, and geographical extent, relatively little research focuses on the role of loss processes in blooms and how these processes are regulated. Here, we define a loss process in terms of population dynamics as any process that removes cells from a population, thereby decelerating or reducing the development and extent of blooms. We review abiotic (e.g., hydraulic flushing and oxidative stress/UV light) and biotic factors (e.g., allelopathic compounds, infections, grazing, and resting cells/programmed cell death) known to govern bloom loss. We found that the dominant loss processes depend on several system specific factors including cyanobacterial genera -specific traits, in situ physicochemical conditions, and the microbial, phytoplankton, and consumer community composition. We also address loss processes in the context of bloom management and discuss perspectives and challenges in predicting how a changing climate may directly and indirectly affect loss processes on blooms. A deeper understanding of bloom loss processes and their underlying mechanisms may help to mitigate the negative consequences of cyanobacterial blooms and improve current management strategies.
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| 16. |
- Martin, S, et al.
(author)
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Pre-validation of a reporter gene assay for oxidative stress for the rapid screening of nanobiomaterials
- 2022
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In: Frontiers in toxicology. - : Frontiers Media SA. - 2673-3080. ; 4, s. 974429-
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Journal article (peer-reviewed)abstract
- Engineered nanomaterials have been found to induce oxidative stress. Cellular oxidative stress, in turn, can result in the induction of antioxidant and detoxification enzymes which are controlled by the nuclear erythroid 2-related factor 2 (NRF2) transcription factor. Here, we present the results of a pre-validation study which was conducted within the frame of BIORIMA (“biomaterial risk management”) an EU-funded research and innovation project. For this we used an NRF2 specific chemically activated luciferase expression reporter gene assay derived from the human U2OS osteosarcoma cell line to screen for the induction of the NRF2 mediated gene expression following exposure to biomedically relevant nanobiomaterials. Specifically, we investigated Fe3O4-PEG-PLGA nanomaterials while Ag and TiO2 “benchmark” nanomaterials from the Joint Research Center were used as reference materials. The viability of the cells was determined by using the Alamar blue assay. We performed an interlaboratory study involving seven different laboratories to assess the applicability of the NRF2 reporter gene assay for the screening of nanobiomaterials. The latter work was preceded by online tutorials to ensure that the procedures were harmonized across the different participating laboratories. Fe3O4-PEG-PLGA nanomaterials were found to induce very limited NRF2 mediated gene expression, whereas exposure to Ag nanomaterials induced NRF2 mediated gene expression. TiO2 nanomaterials did not induce NRF2 mediated gene expression. The variability in the results obtained by the participating laboratories was small with mean intra-laboratory standard deviation of 0.16 and mean inter laboratory standard deviation of 0.28 across all NRF2 reporter gene assay results. We conclude that the NRF2 reporter gene assay is a suitable assay for the screening of nanobiomaterial-induced oxidative stress responses.
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