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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Carreira, Bruno Pereira, et al. (författare)
  • Nitric Oxide Stimulates the Proliferation of Neural Stem Cells Bypassing the Epidermal Growth Factor Receptor
  • 2010
  • Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 28:7, s. 1219-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitric oxide (NO) was described to inhibit the proliferation of neural stem cells. Some evidence suggests that NO, under certain conditions, can also promote cell proliferation, although the mechanisms responsible for a potential proliferative effect of NO in neural stem cells have remained unaddressed. In this work, we investigated and characterized the proliferative effect of NO in cell cultures obtained from the mouse subventricular zone. We found that the NO donor NOC-18 (10 mu M) increased cell proliferation, whereas higher concentrations (100 mu M) inhibited cell proliferation. Increased cell proliferation was detected rapidly following exposure to NO and was prevented by blocking the mitogen-activated kinase (MAPK) pathway, independently of the epidermal growth factor (EGF) receptor. Downstream of the EGF receptor, NO activated p21Ras and the MAPK pathway, resulting in a decrease in the nuclear presence of the cyclin-dependent kinase inhibitor I, p27(KIP1), allowing for cell cycle progression. Furthermore, in a mouse model that shows increased proliferation of neural stem cells in the hippocampus following seizure injury, we observed that the absence of inducible nitric oxide synthase (iNOS(-/-) mice) prevented the increase in cell proliferation observed following seizures in wild-type mice, showing that NO from iNOS origin is important for increased cell proliferation following a brain insult. Overall, we show that NO is able to stimulate the proliferation of neural stem cells bypassing the EGF receptor and promoting cell division. Moreover, under pathophysiological conditions in vivo, NO from iNOS origin also promotes proliferation in the hippocampus. STEM CELLS 2010:28:1219-1230
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3.
  • Lozano, Rafael, et al. (författare)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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4.
  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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5.
  • Amaral, Rita, et al. (författare)
  • Profiling Persistent Asthma Phenotypes in Adolescents : A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies
  • 2021
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.
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6.
  • Baiocchi, Gian Luca, et al. (författare)
  • International consensus on a complications list after gastrectomy for cancer
  • 2019
  • Ingår i: Gastric Cancer. - : Springer Science and Business Media LLC. - 1436-3291 .- 1436-3305. ; 22:1, s. 172-189
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. Methods: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. Results: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. Conclusion: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.
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7.
  • Batista-Santos, Paula, et al. (författare)
  • Is salt stress tolerance in Casuarina glauca Sieb. ex Spreng. associated with its nitrogen-fixing root-nodule symbiosis? An analysis at the photosynthetic level
  • 2015
  • Ingår i: Plant physiology and biochemistry (Paris). - : Elsevier BV. - 0981-9428 .- 1873-2690. ; 96, s. 97-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Casuarina glauca is an actinorhizal tree which establishes root-nodule symbiosis with N-2-fixing Frankia bacteria. This plant is commonly found in saline zones and is widely used to remediate marginal soils and prevent desertification. The nature of its ability to survive in extreme environments and the extent of Frankia contribution to stress tolerance remain unknown. Thus, we evaluated the ability of C. glauca to cope with salt stress and the influence of the symbiosis on this trait. To this end, we analysed the impact of salt on plant growth, mineral contents, water relations, photosynthetic-related parameters and nonstructural sugars in nodulated vs. non-nodulated plants. Although the effects on photosynthesis and stomatal conductance started to become measurable in the presence of 200 mM NaCl, photochemical (e.g., photosynthetic electron flow) and biochemical (e.g., activity of photosynthetic enzymes) parameters were only strongly impaired when NaCl levels reached 600 mM. These results indicate the maintenance of high tissue hydration under salt stress, probably associated with enhanced osmotic potential. Furthermore, the maintenance of photosynthetic assimilation potential (A(max)), together with the increase in the quantum yield of down-regulated energy dissipation of PSII (Y-NPQ), suggested a down-regulation of photosynthesis instead of photo-damaging effects. A comparison of the impact of increasing NaCl levels on the activities of photosynthetic (RubisCO and ribulose-5 phosphate kinase) and respiratory (pyruvate kinase and NADH-dependent malate dehydrogenase) enzymes vs. photosynthetic electron flow and fluorescence parameters, revealed that biochemical impairments are more limiting than photochemical damage. Altogether, these results indicate that, under controlled conditions, C glauca tolerates high NaCl levels and that this capacity is linked to photosynthetic adjustments.
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8.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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9.
  • Boons, Frank, et al. (författare)
  • Comparing industrial symbiosis in Europe : towards a conceptual framework and research methodology
  • 2015
  • Ingår i: International perspectives on industrial ecology. - Cheltenham : Edward Elgar Publishing. - 9781781003565 - 9781781003572 ; , s. 69-88
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Industrial symbiosis (IS) continues to raise the interest of researchers and practitioners alike. Individual and haphazard attempts to increase linkages among co-located firms have been complemented by concerted efforts to stimulate the development of industrial regions with intensified resource exchanges that reduce environmental impact. Additionally, there are examples of both spontaneous and facilitated linkages between two or more firms involving flows of materials/energy waste. A striking feature of IS activities is that they are found across diverse social contexts and vary considerably in form (Lombardi et al., 2012); there are substantial differences in the ways in which IS manifests itself. Equally diverse are the activities of policy makers to stimulate such linkages. Such diversity can already be found within Europe, as became apparent in a first meeting among some of the present authors in 2009 (Isenmann and Chernykh, 2009). Researchers present there decided to create a network of European researchers on IS, with the explicit aim to develop a comparative analysis. We can thus provide insight to the relationship between the style of IS and its context and thereby the potential for policy makers in different contexts to learn from each other. Policy learning can be a tempting route to IS, but is fraught with difficulties if the influence of context is not appreciated (e.g., Wang et al., Chapter 6, this volume).
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10.
  • Boons, Frank, et al. (författare)
  • Mapping the Diversity of Industrial Symbiosis: Comparative analysis of European public and private efforts to develop symbiotic networks
  • 2013
  • Ingår i: 7th International Society for industrial Ecology Biennial Conference.
  • Konferensbidrag (refereegranskat)abstract
    • The paper presents ongoing research performed by a network of European researchers on the development and diffusion of industrial symbiosis in European countries. The research has a number of aims:1. To find out the nature of industrial symbiosis by finding out the national peculiarities as well as points of correspondence in countries with varying characteristics in socio-economic institutions;2. To map the process of diffusion of industrial symbiosis within and across European countries;3. To find unique and corresponding elements in the (public and private) efforts to stimulate industrial symbiosis.The paper will present main results from the analysis of our cross-national dataset covering these dimensions. It will show the highly specific nature in which symbiosis is defined and diffuse in each country. This leads to a reflection on the way in which industrial symbiosis research should develop more extended typologies of forms of symbiotic networks that are sensitive to these differences. The paper will also reflect on the methods we used to perform this research, and the learning curve we experienced in doing so. This experience is valuable for future research efforts to extend the comparison to other parts of the world, and compare European with American and Asian developments.
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