| 1. |
- Witjes, J. Alfred, et al.
(author)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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| 2. |
- Surendran, Praveen, et al.
(author)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 3. |
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| 4. |
- Christopoulos, Arthur, et al.
(author)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
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In: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
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Research review (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 5. |
- Cuni-Sanchez, Aida, et al.
(author)
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High aboveground carbon stock of African tropical montane forests
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
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Journal article (peer-reviewed)abstract
- Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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| 6. |
- Helland, Ragnhild Holden, et al.
(author)
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Segmentation of glioblastomas in early post-operative multi-modal MRI with deep neural networks.
- 2023
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In: Scientific reports. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61% Dice score, and the best classification performance was about 80% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection.
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| 7. |
- Kuliński, Karol, et al.
(author)
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Biogeochemical functioning of the Baltic Sea
- 2022
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In: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 13, s. 633-685
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Research review (peer-reviewed)abstract
- Location, specific topography, and hydrographic setting together with climate change and strong anthropogenic pressure are the main factors shaping the biogeochemical functioning and thus also the ecological status of the Baltic Sea. The recent decades have brought significant changes in the Baltic Sea. First, the rising nutrient loads from land in the second half of the 20th century led to eutrophication and spreading of hypoxic and anoxic areas, for which permanent stratification of the water column and limited ventilation of deep-water layers made favourable conditions. Since the 1980s the nutrient loads to the Baltic Sea have been continuously decreasing. This, however, has so far not resulted in significant improvements in oxygen availability in the deep regions, which has revealed a slow response time of the system to the reduction of the land-derived nutrient loads. Responsible for that is the low burial efficiency of phosphorus at anoxic conditions and its remobilization from sediments when conditions change from oxic to anoxic. This results in a stoichiometric excess of phosphorus available for organic-matter production, which promotes the growth of N2-fixing cyanobacteria and in turn supports eutrophication. This assessment reviews the available and published knowledge on the biogeochemical functioning of the Baltic Sea. In its content, the paper covers the aspects related to changes in carbon, nitrogen, and phosphorus (C, N, and P) external loads, their transformations in the coastal zone, changes in organic-matter production (eutrophication) and remineralization (oxygen availability), and the role of sediments in burial and turnover of C, N, and P. In addition to that, this paper focuses also on changes in the marine CO2 system, the structure and functioning of the microbial community, and the role of contaminants for biogeochemical processes. This comprehensive assessment allowed also for identifying knowledge gaps and future research needs in the field of marine biogeochemistry in the Baltic Sea. Copyright:
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| 8. |
- Müller, Matias I.
(author)
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Learning Sequential Decision Rules in Control Design: Regret-Optimal and Risk-Coherent Methods
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Engineering sciences deal with the problem of optimal design in the face of uncertainty. In particular, control engineering is concerned about designing policies/laws/algorithms that sequentially take decisions given unreliable data. This thesis addresses two particular instances of optimal sequential decision making for two different problems.The first problem is known as the H∞-norm (or, in general, ℓ2-gain for nonlinear systems) estimation problem, which is a fundamental quantity in control design through, e.g., the small gain theorem. Given an unknown system, the goal is to find the maximum ℓ2-gain which, in a model-free approach, involves solving a sequential input design problem. The H∞-norm estimation problem (or simply "gain estimation problem") is cast as the composition of multi-armed bandit problem generating data, and an optimal estimation problem given that data. The problem of generating data is a sequential input-design problem in which, at every round, the decision-maker chooses one (or many) frequencies to sample from the unknown frequency response of the system under study. We show that Thompson Sampling (TS), a classical bandit algorithm, is optimal within the class of algorithms that chooses only one frequency per round. Additionally, we introduce Weighted Thompson Sampling (WTS), which is a TS-based algorithm that can sample many frequencies at every round. In this thesis, we prove that WTS is an optimal bandit policy within the class of algorithms that can sample many frequencies simultaneously. On the other hand, the problem of estimating the H∞-norm of the system using the data provided by the bandit algorithm is also discussed. In particular, we show that the expected estimation error of the gain of the system asymptotically matches the Cramér-Rao lower bound for a proposed estimator, and for every bandit policy in a wide class of algorithms.In the second part, we address the problem of risk-coherent optimal control design for disturbance rejection under uncertainty, where optimality is studied from an H2 and an H∞ sense. We consider a parametric model for the plant and the noise spectrum, where the modeling error between the model and the real system is uncertain. This uncertainty is condensed in a probability density function over the different realizations of the parameters defining the model. We use this information to design a controller that minimizes the risk of falling into poor closed-loop performance within a financial theory of risk framework. When the parameters in the plant are not known with sufficient accuracy for control purposes, we introduce a framework that allows us to tackle the joint-stabilization problem by means of sequential convex relaxations, each of them leading to a semi-definite program. On the other hand, when the noise spectrum is uncertain, we propose a systematic scenario approach for designing H2- and H∞-optimal controllers in terms of quadratically-constrained linear programs and sequential semi-definite programming, respectively. Simulations show that, from a risk-theoretical perspective, exploiting the information encoded in the probability density function of the parameters defining the models better balances the risk of falling into poor closed-loop performances.
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| 9. |
- Sieberer, Ulrich, et al.
(author)
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The Political Dynamics of Portfolio Design in European Democracies
- 2021
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In: British Journal of Political Science. - : Cambridge University Press. - 0007-1234 .- 1469-2112. ; 51:2, s. 772-787
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Journal article (peer-reviewed)abstract
- The design of government portfolios – that is, the distribution of competencies among government ministries and office holders – has been largely ignored in the study of executive and coalition politics. This article argues that portfolio design is a substantively and theoretically relevant phenomenon that has major implications for the study of institutional design and coalition politics. The authors use comparative data on portfolio design reforms in nine Western European countries since the 1970s to demonstrate how the design of government portfolios changes over time. Specifically, they show that portfolios are changed frequently (on average about once a year) and that such shifts are more likely after changes in the prime ministership or the party composition of the government. These findings suggest a political logic behind these reforms based on the preferences and power of political parties and politicians. They have major implications for the study of institutional design and coalition politics.
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| 10. |
- Simoni, Mark U., et al.
(author)
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Mass-Balance-Consistent Geological Stock Accounting: A New Approach toward Sustainable Management of Mineral Resources
- 2024
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 58:2, s. 971-990
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Research review (peer-reviewed)abstract
- Global resource extraction raises concerns about environmental pressures and the security of mineral supply. Strategies to address these concerns depend on robust information on natural resource endowments, and on suitable methods to monitor and model their changes over time. However, current mineral resources and reserves reporting and accounting workflows are poorly suited for addressing mineral depletion or answering questions about the long-term sustainable supply. Our integrative review finds that the lack of a robust theoretical concept and framework for mass-balance (MB)-consistent geological stock accounting hinders systematic industry-government data integration, resource governance, and strategy development. We evaluate the existing literature on geological stock accounting, identify shortcomings of current monitoring of mine production, and outline a conceptual framework for MB-consistent system integration based on material flow analysis (MFA). Our synthesis shows that recent developments in Earth observation, geoinformation management, and sustainability reporting act as catalysts that make MB-consistent geological stock accounting increasingly feasible. We propose first steps for its implementation and anticipate that our perspective as “resource realists” will facilitate the integration of geological and anthropogenic material systems, help secure future mineral supply, and support the global sustainability transition.
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| 11. |
- Virkki, Vili, et al.
(author)
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Globally widespread and increasing violations of environmental flow envelopes
- 2022
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In: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 26:12, s. 3315-3336
-
Journal article (peer-reviewed)abstract
- Human actions and climate change have drastically altered river flows across the world, resulting in adverse effects on riverine ecosystems. Environmental flows (EFs) have emerged as a prominent tool for safeguarding the riverine ecosystems, but at the global scale, the assessment of EFs is associated with high uncertainty related to the hydrological data and EF methods employed. Here, we present a novel, in-depth global EF assessment using environmental flow envelopes (EFEs). Sub-basin-specific EFEs are determined for approximately 4400 sub-basins at a monthly time resolution, and their derivation considers the methodological uncertainties related to global-scale EF studies. In addition to a lower bound of discharge based on existing EF methods, we introduce an upper bound of discharge in the EFE. This upper bound enables areas to be identified where streamflow has substantially increased above natural levels. Further, instead of only showing whether EFs are violated over a time period, we quantify, for the first time, the frequency, severity, and trends of EFE violations during the recent historical period.Discharge was derived from global hydrological model outputs from the ISIMIP 2b ensemble. We use pre-industrial (1801–1860) quasi-natural discharge together with a suite of hydrological EF methods to estimate the EFEs. We then compare the EFEs with recent historical (1976–2005) discharge to assess the violations of the EFE. These violations most commonly manifest as insufficient streamflow during the low-flow season, with fewer violations during the intermediate-flow season, and only a few violations during the high-flow season. The EFE violations are widespread and occur in half of the sub-basins of the world during more than 5 % of the months between 1976 and 2005, which is double compared with the pre-industrial period. The trends in EFE violations have mainly been increasing, which will likely continue in the future with the projected hydroclimatic changes and increases in anthropogenic water use. Indications of increased upper extreme streamflow through EFE upper bound violations are relatively scarce and dispersed. Although local fine-tuning is necessary for practical applications, and further research on the coupling between quantitative discharge and riverine ecosystem responses at the global scale is required, the EFEs provide a quick and globally robust way of determining environmental flow allocations at the sub-basin scale to inform global research and policies on water resources management.
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| 12. |
- von Scheibler, Emma N.M.M., et al.
(author)
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Parkinsonism in Genetic Neurodevelopmental Disorders : A Systematic Review
- 2023
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In: Movement Disorders Clinical Practice. - : Wiley. - 2330-1619. ; 10:1, s. 17-31
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Research review (peer-reviewed)abstract
- Background: With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we aimed to provide a comprehensive overview of reports on parkinsonism in genetic neurodevelopmental disorders and summarize findings related to genetic diagnosis, clinical features and proposed disease mechanisms. Methods: A systematic literature review was conducted in PubMed and Embase on June 15, 2021. Search terms for parkinsonism and genetic neurodevelopmental disorders, using generic terms and the Human Phenotype Ontology, were combined. Study characteristics and descriptive data were extracted from the articles using a modified version of the Cochrane Consumers and Communication Review Group's data extraction template. The protocol was registered in PROSPERO (CRD42020191035). Results: The literature search yielded 208 reports for data-extraction, describing 69 genetic disorders in 422 patients. The five most reported from most to least frequent were: 22q11.2 deletion syndrome, beta-propeller protein-associated neurodegeneration, Down syndrome, cerebrotendinous xanthomatosis, and Rett syndrome. Notable findings were an almost equal male to female ratio, an early median age of motor onset (26 years old) and rigidity being more common than rest tremor. Results of dopaminergic imaging and response to antiparkinsonian medication often supported the neurodegenerative nature of parkinsonism. Moreover, neuropathology results showed neuronal loss in the majority of cases. Proposed disease mechanisms included aberrant mitochondrial function and disruptions in neurotransmitter metabolism, endosomal trafficking, and the autophagic-lysosomal and ubiquitin-proteasome system. Conclusion: Parkinsonism has been reported in many GNDs. Findings from this study may provide clues for further research and improve management of patients with GNDs and/or parkinsonism.
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| 13. |
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