| 1. |
- Bjegovic-Mikanovic, Vesna, et al.
(författare)
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Developing The Publichealth Workforce
- 2015
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Ingår i: Eurohealth. - : London School of Economics and Political Science. - 1356-1030. ; 21:1, s. 24-27
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The development of the public health workforce is acornerstone in WHO's Action Plan for Strengthening Public HealthServices and Capacities. Public health education shall combineEssential Public Health Operations – surveillance; monitoring; healthprotection and promotion; disease prevention; service delivery;communication and research – with the competences needed within:public health methods; population health and its social, economicand environmental determinants; and man-made systems andinterventions to improve population health. An authorised publichealth profession founded on graduation from comprehensive publichealth education is needed. The capacity and standards of Schoolsof Public Health should accordingly be continuously developed.
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| 2. |
- Bramsen, Jesper B., et al.
(författare)
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A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity
- 2009
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Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 37:9, s. 2867-2881
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Tidskriftsartikel (refereegranskat)abstract
- The use of chemically synthesized short interfering RNAs (siRNAs) is currently the method of choice to manipulate gene expression in mammalian cell culture, yet improvements of siRNA design is expectably required for successful application in vivo. Several studies have aimed at improving siRNA performance through the introduction of chemical modifications but a direct comparison of these results is difficult. We have directly compared the effect of 21 types of chemical modifications on siRNA activity and toxicity in a total of 2160 siRNA duplexes. We demonstrate that siRNA activity is primarily enhanced by favouring the incorporation of the intended antisense strand during RNA-induced silencing complex (RISC) loading by modulation of siRNA thermodynamic asymmetry and engineering of siRNA 3'-overhangs. Collectively, our results provide unique insights into the tolerance for chemical modifications and provide a simple guide to successful chemical modification of siRNAs with improved activity, stability and low toxicity.
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| 3. |
- Cederquist, Kristina, et al.
(författare)
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Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 109:3, s. 370-376
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder that predisposes to predominantly colorectal and endometrial cancers due to germline mutations in DNA mismatch repair genes, mainly MLH1, MSH2 and in families with excess endometrial cancer also MSH6. In this population-based study, we analysed the mutation spectrum of the MLH1, MSH2 and MSH6 genes in a cohort of patients with microsatellite unstable double primary tumours of the colorectum and the endometrium by PCR, DHPLC and sequencing. Fourteen of the 23 patients (61%) had sequence variants in MLH1, MSH2 or MSH6 that likely affect the protein function. A majority (10/14) of the mutations was found among probands diagnosed before age 50. Five of the mutations (36%) were located in MLH1, 3 (21%) in MSH2 and 6 (43%) in MSH6. MSH6 seem to have larger impact in our population than in other populations, due to a founder effect since all of the MSH6 families originate from the same geographical area. MSH6 mutation carriers have later age of onset of both colorectal cancer (62 vs. 51 years) and endometrial cancer (58 vs. 48 years) and a larger proportion of endometrial cancer than MLH1 or MSH2 mutation carriers. We can conclude that patients with microsatellite unstable double primary cancers of the colorectum and the endometrium have a very high risk of carrying a mutation not only in MLH1 or MSH2 but also in MSH6, especially if they get their first cancer diagnosis before the age of 50. Copyright 2004 Wiley-Liss, Inc.
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| 4. |
- Dasgupta, Indranil, et al.
(författare)
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Validating the use of bioimpedance spectroscopy for assessment of fluid status in children.
- 2018
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Ingår i: Pediatric nephrology. - : Springer Science and Business Media LLC. - 1432-198X .- 0931-041X. ; 33:9, s. 1601-1607
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Tidskriftsartikel (refereegranskat)abstract
- Bioimpedance spectroscopy (BIS) with a whole-body model to distinguish excess fluid from major body tissue hydration can provide objective assessment of fluid status. BIS is integrated into the Body Composition Monitor (BCM) and is validated in adults, but not children. This study aimed to (1) assess agreement between BCM-measured total body water (TBW) and a gold standard technique in healthy children, (2) compare TBW_BCM with TBW from Urea Kinetic Modelling (UKM) in haemodialysis children and (3) investigate systematic deviation from zero in measured excess fluid in healthy children across paediatric age range.TBW_BCM and excess fluid was determined from standard wrist-to-ankle BCM measurement. TBW_D2O was determined from deuterium concentration decline in serial urine samples over 5days in healthy children. UKM was used to measure body water in children receiving haemodialysis. Agreement between methods was analysed using paired t test and Bland-Altman method comparison.In 61 healthy children (6-14years, 32 male), mean TBW_BCM and TBW_D2O were 21.1±5.6and 20.5±5.8L respectively. There was good agreement between TBW_BCM and TBW_D2O (R2=0.97). In six haemodialysis children (4-13years, 4 male), 45 concomitant measurements over 8months showed good TBW_BCM and TBW_UKM agreement (mean difference -0.4L, 2SD=±3.0L). In 634 healthy children (2-17years, 300 male), BCM-measured overhydration was -0.1±0.7L (10-90th percentile -0.8 to+0.6L). There was no correlation between age and OH (p=0.28).These results suggest BCM can be used in children as young as 2years to measure normally hydrated weight and assess fluid status.
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| 5. |
- Gawlik, Darius, et al.
(författare)
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Molecular investigations on a chimeric strain of Staphylococcus aureus sequence type 80
- 2020
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- A PVL-positive, methicillin-susceptible Staphylococcus aureus was cultured from pus from cervical lymphadenitis of a patient of East-African origin. Microarray hybridisation assigned the isolate to clonal complex (CC) 80 but revealed unusual features, including the presence of the ORF-CM14 enterotoxin homologue and of an ACME-III element as well as the absence of etD and edinB. The isolate was subjected to both, Illumina and Nanopore sequencing allowing characterisation of deviating regions within the strain´s genome. Atypical features of this strain were attributable to the presence of two genomic regions that originated from other S. aureus lineages and that comprised, respectively, 3% and 1.4% of the genome. One deviating region extended from walJ to sirB. It comprised ORF-CM14 and the ACME-III element. A homologous but larger fragment was also found in an atypical S. aureus CC1/ST567 strain whose lineage might have served as donor of this genomic region. This region itself is a chimera comprising fragments from CC1 as well as fragments of unknown origin. The other deviating region comprised the region from htsB to ecfA2, i.e., another 3% of the genome. It was very similar to CC1 sequences. Either this suggests an incorporation of CC1 DNA into the study strain, or alternatively a recombination event affecting "canonical" CC80. Thus, the study strain bears witness of several recombination events affecting supposedly core genomic genes. Although the exact mechanism is not yet clear, such chimerism seems to be an additional pathway in the evolution of S. aureus. This could facilitate also a transmission of virulence and resistance factors and therefore offer an additional evolutionary advantage.
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| 6. |
- Hagger, Martin S., et al.
(författare)
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A Multilab Preregistered Replication of the Ego-Depletion Effect
- 2016
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Ingår i: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 11:4, s. 546-573
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Tidskriftsartikel (refereegranskat)abstract
- Good self-control has been linked to adaptive outcomes such as better health, cohesive personal relationships, success in the workplace and at school, and less susceptibility to crime and addictions. In contrast, self-control failure is linked to maladaptive outcomes. Understanding the mechanisms by which self-control predicts behavior may assist in promoting better regulation and outcomes. A popular approach to understanding self-control is the strength or resource depletion model. Self-control is conceptualized as a limited resource that becomes depleted after a period of exertion resulting in self-control failure. The model has typically been tested using a sequential-task experimental paradigm, in which people completing an initial self-control task have reduced self-control capacity and poorer performance on a subsequent task, a state known as ego depletion. Although a meta-analysis of ego-depletion experiments found a medium-sized effect, subsequent meta-analyses have questioned the size and existence of the effect and identified instances of possible bias. The analyses served as a catalyst for the current Registered Replication Report of the ego-depletion effect. Multiple laboratories (k = 23, total N = 2,141) conducted replications of a standardized ego-depletion protocol based on a sequential-task paradigm by Sripada et al. Meta-analysis of the studies revealed that the size of the ego-depletion effect was small with 95% confidence intervals (CIs) that encompassed zero (d = 0.04, 95% CI [-0.07, 0.15]. We discuss implications of the findings for the ego-depletion effect and the resource depletion model of self-control.
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| 7. |
- Horneck, Gerda, et al.
(författare)
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AstRoMap European Astrobiology Roadmap
- 2016
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Ingår i: Astrobiology. - : Mary Ann Liebert. - 1531-1074 .- 1557-8070. ; 16:3, s. 201-243
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Forskningsöversikt (refereegranskat)abstract
- The European AstRoMap project (supported by the European Commission Seventh Framework Programme) surveyed the state of the art of astrobiology in Europe and beyond and produced the first European roadmap for astrobiology research. In the context of this roadmap, astrobiology is understood as the study of the origin, evolution, and distribution of life in the context of cosmic evolution; this includes habitability in the Solar System and beyond. The AstRoMap Roadmap identifies five research topics, specifies several key scientific objectives for each topic, and suggests ways to achieve all the objectives. The five AstRoMap Research Topics are• Research Topic 1: Origin and Evolution of Planetary Systems• Research Topic 2: Origins of Organic Compounds in Space• Research Topic 3: Rock-Water-Carbon Interactions, Organic Synthesis on Earth, and Steps to Life• Research Topic 4: Life and Habitability• Research Topic 5: Biosignatures as Facilitating Life DetectionIt is strongly recommended that steps be taken towards the definition and implementation of a European Astrobiology Platform (or Institute) to streamline and optimize the scientific return by using a coordinated infrastructure and funding system.
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| 8. |
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| 9. |
- Krause, Andreas, et al.
(författare)
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Large uncertainty in carbon uptake potential of land-based climate-change mitigation efforts
- 2018
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013. ; 24:7, s. 3025-3038
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Tidskriftsartikel (refereegranskat)abstract
- Most climate mitigation scenarios involve negative emissions, especially those that aim to limit global temperature increase to 2°C or less. However, the carbon uptake potential in land-based climate change mitigation efforts is highly uncertain. Here, we address this uncertainty by using two land-based mitigation scenarios from two land-use models (IMAGE and MAgPIE) as input to four dynamic global vegetation models (DGVMs; LPJ-GUESS, ORCHIDEE, JULES, LPJmL). Each of the four combinations of land-use models and mitigation scenarios aimed for a cumulative carbon uptake of ~130 GtC by the end of the century, achieved either via the cultivation of bioenergy crops combined with carbon capture and storage (BECCS) or avoided deforestation and afforestation (ADAFF). Results suggest large uncertainty in simulated future land demand and carbon uptake rates, depending on the assumptions related to land use and land management in the models. Total cumulative carbon uptake in the DGVMs is highly variable across mitigation scenarios, ranging between 19 and 130 GtC by year 2099. Only one out of the 16 combinations of mitigation scenarios and DGVMs achieves an equivalent or higher carbon uptake than achieved in the land-use models. The large differences in carbon uptake between the DGVMs and their discrepancy against the carbon uptake in IMAGE and MAgPIE are mainly due to different model assumptions regarding bioenergy crop yields and due to the simulation of soil carbon response to land-use change. Differences between land-use models and DGVMs regarding forest biomass and the rate of forest regrowth also have an impact, albeit smaller, on the results. Given the low confidence in simulated carbon uptake for a given land-based mitigation scenario, and that negative emissions simulated by the DGVMs are typically lower than assumed in scenarios consistent with the 2°C target, relying on negative emissions to mitigate climate change is a highly uncertain strategy.
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| 10. |
- Lozano, Rafael, et al.
(författare)
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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
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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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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