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- van Rheenen, W, et al.
(författare)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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- Glasier, A, et al.
(författare)
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ISGE statement on oral emergency contraception
- 2014
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Ingår i: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. - : Informa UK Limited. - 1473-0766. ; 30:10, s. 681-682
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Gruber, G, et al.
(författare)
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Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer.
- 2008
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 1569-8041. ; 19:8, s. 1393-401
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.
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- Pagani, Olivia, et al.
(författare)
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Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93.
- 2009
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Ingår i: Breast cancer research and treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 116:3, s. 491-500
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Tidskriftsartikel (refereegranskat)abstract
- To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.
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- Ferrari, P., et al.
(författare)
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Testing facility for the characterization of the integration of E-vehicles into smart grid in presence of renewable energy
- 2019
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Ingår i: Lecture Notes in Electrical Engineering. - Cham : Springer Verlag. - 9783030119720 ; , s. 19-25
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Konferensbidrag (refereegranskat)abstract
- In the last years, the increased environmental awareness is calling for the transition from vehicles powered by Internal Combustion Engines (ICEs) toward Electric Vehicles (EVs). Nevertheless, the wide penetration of such technologies is limited by the impact EV Charging Stations (EVCSs) have on the distribution grid. The management of EVCSs could benefit from the use of the energy produced by Renewable Resources, appropriately coupled with storage system, through the infrastructures offered by Smart Grids (SGs). The validation of these architectures can be performed in simulation or emulation environments. Whilst such approaches are profitable for validating the sensitivity of different architectures to parameters changes, sometimes the use of over-simplified models could bring to unreliable results. For this reason, a testing facility for the characterization of the integration of EVCSs in SGs has been designed and deployed at the eLUX lab of the University of Brescia, Italy. The testing facility includes an EVCS (22 kW), an EV (Renault Zoe), a controllable photovoltaic (PV) field (10 kWp) and a Battery Energy Storage System (BESS) (20 kWp, 23.5 kWh). The possibility to integrate a real-time emulator (OPAL-RT) for Hardware-In-the-Loop (HIL) emulation allows to easily expand the capabilities of the testing facility. © 2019, Springer Nature Switzerland AG.
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| 10. |
- Gruber, Günther, et al.
(författare)
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Prognostic value of extracapsular tumor spread for locoregional control in premenopausal patients with node-positive breast cancer treated with classical cyclophosphamide, methotrexate, and fluorouracil: long-term observations from International Breast Cancer Study Group Trial VI.
- 2005
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 23:28, s. 7089-97
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We sought to determine retrospectively whether extracapsular spread (ECS) might identify a subgroup that could benefit from radiotherapy after mastectomy, especially patients with 1 to 3 positive lymph nodes (LN1-3+). PATIENTS AND METHODS: We randomized 1,475 premenopausal women with node-positive breast cancer to three, six, or nine courses of "classical" CMF (cyclophosphamide, methotrexate, and fluorouracil). After a review of all pathology forms, 933 patients (63%) had information on the presence or absence of ECS. ECS was present in 49.5%. The median follow-up was 10 years. RESULTS: In univariate analyses, ECS was associated with worse disease-free survival (DFS) and overall survival (OS). In multivariate analyses adjusting for tumor size, vessel invasion, surgery type, and age group, ECS remained significant (DFS: hazard ratio, 1.61; 95% CI, 1.34 to 1.93; P < .0001; OS: 1.67; 95% CI, 1.34 to 2.08; P < .0001). However, ECS was not significant when the number of positive nodes was added. The locoregional failure rate +/- distant failure (LRF +/- distant failure) within 10 years was estimated at 19% (+/- 2%) without ECS, versus 27% (+/- 2%) with ECS. The difference was statistically significant in univariate analyses, but not after adjusting for the number of positive nodes. No independent effect of ECS on DFS, OS, or LRF could be confirmed within the subgroup of 382 patients with LN1-3+ treated with mastectomy without radiotherapy. CONCLUSION: Our results do not support an independent prognostic value of ECS, nor its use as an indication for irradiation in premenopausal patients with LN1-3+ treated with classical CMF. However, we could not examine whether extensive ECS is of prognostic importance.
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| 11. |
- Kenward, R. E., et al.
(författare)
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Identifying governance strategies that effectively support ecosystem services, resource sustainability, and biodiversity
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:13, s. 5308-5312
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Tidskriftsartikel (refereegranskat)abstract
- Conservation scientists, national governments, and international conservation groups seek to devise, and implement, governance strategies that mitigate human impact on the environment. However, few studies to date have systematically investigated the performance of different systems of governance in achieving successful conservation outcomes. Here, we use a newly-developed analytic framework to conduct analyses of a suite of case studies, linking different governance strategies to standardized scores for delivering ecosystem services, achieving sustainable use of natural resources, and conserving biodiversity, at both local and international levels. Our results: (i) confirm the benefits of adaptive management; and (ii) reveal strong associations for the role of leadership. Our work provides a critical step toward implementing empirically justified governance strategies that are capable of improving the management of human-altered environments, with benefits for both biodiversity and people.
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- Rinaldi, S., et al.
(författare)
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A Testing Framework for the Monitoring and Performance Analysis of Distributed Energy Systems
- 2019
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Ingår i: IEEE Transactions on Instrumentation and Measurement. - : Institute of Electrical and Electronics Engineers Inc.. - 0018-9456 .- 1557-9662. ; 68:10, s. 3831-3840
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Tidskriftsartikel (refereegranskat)abstract
- The increasing presence of intermittent distributed generation (DG) based on renewable energy sources (RESs) is heavily affecting the operation and management of modern distribution grids. Even though the use of distributed energy storage systems (DESSs) and the integration of advanced demand response (DR) programs are expected to mitigate this problem, security, safety, economic, and technical reasons are limiting the tests of these mechanisms in working systems. The test in simulation and emulation environments has proved to be an effective solution for the development of advanced control and protection schema, but their use for the simulation of the typically unpredictable behavior of end-users seems at least questionable. This paper proposes a testing framework for the analysis of experimental control strategies of distributed energy systems. The framework, based on a service-oriented architecture, can be easily interconnected to different systems, including renewable generators and storage systems. This framework can be used to analyze the performance of real energy systems, working in near-To-real conditions. The framework has been used for a pilot test on a subset of the facilities of the eLUX laboratory of the University of Brescia. The proposed framework allows analyzing the energy performance of this system by means of proper key performance indicators (KPIs). The efficiency analysis of a battery energy storage system (BESS) is presented, by proposing KPIs to evaluate the effect of different control strategies. Further KPIs are also used to evaluate the effectiveness of the BESS for improving the energy self-consumption of a photovoltaic system. © 1963-2012 IEEE.
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