| 1. |
- Bausch, Birke, et al.
(author)
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Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention
- 2017
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In: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:9, s. 1204-1212
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Journal article (peer-reviewed)abstract
- IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
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| 2. |
- Krauss, Tobias, et al.
(author)
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Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors
- 2018
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In: Endocrine-Related Cancer. - : BIOSCIENTIFICA LTD. - 1351-0088 .- 1479-6821. ; 25:9, s. 783-793
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Journal article (peer-reviewed)abstract
- Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were >= 2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off >= 2.8 cm, 44% and 91% for TVDT cut-off of <= 24 months). In 117 of 273 patients, PanNETs > 1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs < 2.8 cm vs >= 2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.
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| 3. |
- Nilsson, Måns, et al.
(author)
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Mapping interactions between the sustainable development goals : lessons learned and ways forward
- 2018
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In: Sustainability Science. - : SPRINGER JAPAN KK. - 1862-4065 .- 1862-4057. ; 13:6, s. 1489-1503
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Journal article (peer-reviewed)abstract
- Pursuing integrated research and decision-making to advance action on the sustainable development goals (SDGs) fundamentally depends on understanding interactions between the SDGs, both negative ones (trade-offs) and positive ones (co-benefits). This quest, triggered by the 2030 Agenda, has however pointed to a gap in current research and policy analysis regarding how to think systematically about interactions across the SDGs. This paper synthesizes experiences and insights from the application of a new conceptual framework for mapping and assessing SDG interactions using a defined typology and characterization approach. Drawing on results from a major international research study applied to the SDGs on health, energy and the ocean, it analyses how interactions depend on key factors such as geographical context, resource endowments, time horizon and governance. The paper discusses the future potential, barriers and opportunities for applying the approach in scientific research, in policy making and in bridging the two through a global SDG Interactions Knowledge Platform as a key mechanism for assembling, systematizing and aggregating knowledge on interactions.
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| 4. |
- Singh, Gerald G., et al.
(author)
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Climate impacts on the ocean are making the Sustainable Development Goals a moving target travelling away from us
- 2019
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In: People and Nature. - : John Wiley & Sons. - 2575-8314. ; 1:3, s. 317-330
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Journal article (peer-reviewed)abstract
- Climate change is impacting marine ecosystems and their goods and services in diverse ways, which can directly hinder our ability to achieve the Sustainable Development Goals (SDGs), set out under the 2030 Agenda for Sustainable Development.Through expert elicitation and a literature review, we find that most climate change effects have a wide variety of negative consequences across marine ecosystem services, though most studies have highlighted impacts from warming and consequences of marine species.Climate change is expected to negatively influence marine ecosystem services through global stressors—such as ocean warming and acidification—but also by amplifying local and regional stressors such as freshwater runoff and pollution load.Experts indicated that all SDGs would be overwhelmingly negatively affected by these climate impacts on marine ecosystem services, with eliminating hunger being among the most directly negatively affected SDG.Despite these challenges, the SDGs aiming to transform our consumption and production practices and develop clean energy systems are found to be least affected by marine climate impacts. These findings represent a strategic point of entry for countries to achieve sustainable development, given that these two goals are relatively robust to climate impacts and that they are important pre-requisite for other SDGs.Our results suggest that climate change impacts on marine ecosystems are set to make the SDGs a moving target travelling away from us. Effective and urgent action towards sustainable development, including mitigating and adapting to climate impacts on marine systems are important to achieve the SDGs, but the longer this action stalls the more distant these goals will become.
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| 5. |
- Todea, Ana Maria, et al.
(author)
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Inter-comparison of personal monitors for nanoparticles exposure at workplaces and in the environment
- 2017
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 605, s. 929-945
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Journal article (peer-reviewed)abstract
- Personal monitors based on unipolar diffusion charging (miniDiSC/DiSCmini, NanoTracer, Partector) can be used to assess the individual exposure to nanoparticles in different environments. The charge acquired by the aerosol particles is nearly proportional to the particle diameter and, by coincidence, also nearly proportional to the alveolar lung-deposited surface area (LDSA), the metric reported by all three instruments. In addition, the miniDiSC/DiSCmini and the NanoTracer report particle number concentration and mean particle size. In view of their use for personal exposure studies, the comparability of these personal monitors was assessed in two measurement a large range of particle sizes, morphologies and concentrations. The data provided by the personal monitors were compared with those obtained from reference instruments: a scanning mobility particle sizer (SMPS) for LDSA and mean particle size and a ultrafine particle counter (UCPC) for number concentration. The results indicated that the LDSA concentrations and the mean particle sizes provided by all investigated instruments in this study were in the order of +/- 30% of the reference value obtained from the SMPS when the particle sizes of the test aerosols generated were within 20-400 nm and the instruments were properly calibrated. Particle size, morphology and concentration did not have a major effect within the aforementioned limits. The comparability of the number concentrations was found to be slightly worse and in the range of +/- 50% of the reference value obtained from the UCPC. In addition, a minor effect of the particle morphology on the number concentration measurements was observed. The presence of particles >400 nm can drastically bias the measurement results of all instruments and all metrics determined.
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