| 1. |
- Dominguez, Mev, et al.
(författare)
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Evaluation of MLH1 I219V Polymorphism in Unrelated South American Individuals Suspected of Having Lynch Syndrome.
- 2012
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Ingår i: Anticancer research. - 1791-7530. ; 32:10, s. 4347-4351
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Tidskriftsartikel (refereegranskat)abstract
- Some single-nucleotide polymorphisms are associated with higher risk of colorectal cancer development and are suggested to explain part of the genetic contribution to Lynch syndrome. Aim: To evaluate the mutL homolog 1 (MLH1) I219V polymorphism in 124 unrelated South American individuals suspected of having Lynch syndrome, based on frequency, association with pathogenic MLH1 and mutS homolog 2 (MSH2) mutation and clinical features.
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| 2. |
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| 3. |
- Dominguez, Mev, et al.
(författare)
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Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals
- 2011
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 10:4, s. 641-647
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Tidskriftsartikel (refereegranskat)abstract
- Lynch syndrome (LS) is an autosomal dominant syndrome that predisposes individuals to development of cancers early in life. These cancers are mainly the following: colorectal, endometrial, ovarian, small intestine, stomach and urinary tract cancers. LS is caused by germline mutations in DNA mismatch repair genes (MMR), mostly MLH1 and MSH2, which are responsible for more than 85% of known germline mutations. To search for germline mutations in MLH1 and MSH2 genes in 123 unrelated South American suspected LS patients (Bethesda or Amsterdam Criteria) DNA was obtained from peripheral blood, and PCR was performed followed by direct sequencing in both directions of all exons and intron-exon junctions regions of the MLH1 and MSH2 genes. MLH1 or MSH2 pathogenic mutations were found in 28.45% (34/123) of the individuals, where 25/57 (43.85%) fulfilled Amsterdam I, II and 9/66 (13.63%) the Bethesda criteria. The mutations found in both genes were as follows: nonsense (35.3%), frameshift (26.47%), splicing (23.52%), and missense (9%). Thirteen alterations (35.14%) were described for the first time. The data reported in this study add new information about MLH1 and MSH2 gene mutations and contribute to better characterize LS in Brazil, Uruguay and Argentina. The high rate of novel mutations demonstrates the importance of defining MLH1 and MSH2 mutations in distinct LS populations.
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| 4. |
- Du, Yiheng, et al.
(författare)
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Application-based evaluation of multi-basin hydrological models
- 2024
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Ingår i: Journal of Hydrology. - 0022-1694. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- Hydrological models are generally calibrated and validated using a suite of well-known statistical metrics, which sometimes lack clear connection and tailoring to the local users’ need and therefore limits the evaluation, especially in the case of global climate services. Therefore, in this study, two types of application-based evaluation metrics are introduced, addressing (i) temporal matching of quantile extremes and (ii) relative bias in flow signatures, which supplements commonly used model performance assessment metrics. The introduced metrics are compared to conventional statistical metrics, at seven case study areas across the world, with three model settings representing different datasets and calibrations, generated from the global hydrological model World-Wide HYPE (WW HYPE). The results suggest that different performance results can occur when comparing application-based metrics to conventional ones. This implies that different evaluation metrics reveal models’ capability in various aspects, supporting their application under the corresponding circumstances. Finally, these metrics enable us to propose two model applicability scenarios: generally applicable models and conditionally applicable models. For instance, the WW HYPE with global dataset and local calibration can yield optimal estimates concerning the timing of quantile extremes and temporal variations in flow signatures, despite its suboptimal performance in conventional evaluation metrics. Therefore, it may be considered as a conditionally applicable model which can be used in regions with limited local datasets, supplying reliable information for decision-makers in formulating strategic plans for water resources management.
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| 5. |
- Freitas, Aline A., et al.
(författare)
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Drought Assessment in São Francisco River Basin, Brazil : Characterization through SPI and Associated Anomalous Climate Patterns
- 2022
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Ingår i: Atmosphere. - : MDPI AG. - 2073-4433. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The São Francisco River Basin (SFRB) is one of the main watersheds in Brazil, standing out for generating energy and consumption, among other ecosystem services. Hence, it is important to identify hydrological drought events and the anomalous climate patterns associated with dry conditions. The Standard Precipitation Index (SPI) for 12 months was used to identify hydrological drought episodes over SFRB 1979 and 2020. For these episodes, the severity, duration, intensity, and peak were obtained, and SPI-1 was applied for the longest and most severe episode to identify months with wet and dry conditions within the rainy season (Nov–Mar). Anomalous atmospheric and oceanic patterns associated with this episode were also analyzed. The results revealed the longest and most severe hydrological drought episode over the basin occurred between 2012 and 2020. The episode over the Upper portion of the basin lasted 103 months. The results showed a deficit of monthly precipitation up to 250 mm in the southeast and northeast regions of the country during the anomalous dry months identified through SPI-1. The dry conditions observed during the rainy season of this episode were associated with an anomalous high-pressure system acting close to the coast of Southeast Brazil, hindering the formation of precipitating systems.
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| 6. |
- Mastellos, Dimitrios C., et al.
(författare)
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Complement C3 vs C5 inhibition in severe COVID-19 : Early clinical findings reveal differential biological efficacy
- 2020
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Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 220
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Tidskriftsartikel (refereegranskat)abstract
- Growing clinical evidence has implicated complement as a pivotal driver of COVID-19 immunopathology. Deregulated complement activation may fuel cytokine-driven hyper-inflammation, thrombotic microangiopathy and NET-driven immunothrombosis, thereby leading to multi-organ failure. Complement therapeutics have gained traction as candidate drugs for countering the detrimental consequences of SARS-CoV-2 infection. Whether blockade of terminal complement effectors (C5, C5a, or C5aR1) may elicit similar outcomes to upstream intervention at the level of C3 remains debated. Here we compare the efficacy of the C5-targeting monoclonal antibody eculizumab with that of the compstatin-based C3-targeted drug candidate AMY-101 in small independent cohorts of severe COVID-19 patients. Our exploratory study indicates that therapeutic complement inhibition abrogates COVID-19 hyper-inflammation. Both C3 and C5 inhibitors elicit a robust anti-inflammatory response, reflected by a steep decline in C-reactive protein and IL-6 levels, marked lung function improvement, and resolution of SARS-CoV-2-associated acute respiratory distress syndrome (ARDS). C3 inhibition afforded broader therapeutic control in COVID-19 patients by attenuating both C3a and sC5b-9 generation and preventing FB consumption. This broader inhibitory profile was associated with a more robust decline of neutrophil counts, attenuated neutrophil extracellular trap (NET) release, faster serum LDH decline, and more prominent lymphocyte recovery. These early clinical results offer important insights into the differential mechanistic basis and underlying biology of C3 and C5 inhibition in COVID-19 and point to a broader pathogenic involvement of C3-mediated pathways in thromboinflammation. They also support the evaluation of these complement-targeting agents as COVID-19 therapeutics in large prospective trials.
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| 8. |
- Sörensen, Johanna Lykke, et al.
(författare)
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Decision Support Indicators (DSIs) and their role in hydrological planning
- 2024
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Ingår i: Environmental Science and Policy. - 1462-9011. ; 157
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Tidskriftsartikel (refereegranskat)abstract
- Decision Support Indicators (DSIs) are metrics designed to inform local and regional stakeholders about the characteristics of a predicted (or ongoing) event to facilitate decision-making. In this paper, the DSI concept was developed to clarify the different aims of different kinds of indicators by naming them, and a framework was developed to describe and support the usage of such DSIs. The framework includes three kinds of DSI: hydroclimatic DSIs which are easy to calculate but hard to understand by non-experts; impact-based DSIs which are often difficult to calculate but easy to understand by non-experts; and event-based DSIs, which compare a current or projected state to a locally well-known historical event, where hydroclimatic and impact-based DSIs are currently mainly used. Tables and figures were developed to support the DSI development in collaboration with stakeholders. To develop and test the framework, seven case studies, representing different hydrological pressures on three continents (South America, Asia, and Europe), were carried out. The case studies span several temporal and spatial scales (hours-decades; 70–6,000 km2) as well as hydrological pressures (pluvial and riverine floods, drought, and water scarcity), representing different climate zones. Based on stakeholder workshops, DSIs were developed for these cases, which are used as examples of the conceptual framework. The adaptability of the DSI framework to this wide range of cases shows that the framework and related concepts are useful in many contexts.
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