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  • Bentham, James, et al. (author)
  • A century of trends in adult human height
  • 2016
  • In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Journal article (peer-reviewed)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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  • Thompson, B.A., et al. (author)
  • Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
  • 2014
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
  • Journal article (peer-reviewed)abstract
    • The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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5.
  • Anderson, J. P., et al. (author)
  • A nearby super-luminous supernova with a long pre-maximum plateau and strong C (II) features
  • 2018
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
  • Journal article (peer-reviewed)abstract
    • Context. Super-luminous supernovae (SLSNe) are rare events defined as being significantly more luminous than normal terminal stellar explosions. The source of the additional power needed to achieve such luminosities is still unclear. Discoveries in the local Universe (i.e. z < 0.1) are scarce, but afford dense multi-wavelength observations. Additional low-redshift objects are therefore extremely valuable.Aims. We present early-time observations of the type I SLSN ASASSN-18km/SN 2018bsz. These data are used to characterise the event and compare to literature SLSNe and spectral models. Host galaxy properties are also analysed.Methods. Optical and near-IR photometry and spectroscopy were analysed. Early-time ATLAS photometry was used to constrain the rising light curve. We identified a number of spectral features in optical-wavelength spectra and track their time evolution. Finally, we used archival host galaxy photometry together with H( II )region spectra to constrain the host environment.Results. ASASSN-18km/SN 2018bsz is found to be a type I SLSN in a galaxy at a redshift of 0.0267 (111 Mpc), making it the lowest-redshift event discovered to date. Strong C- II lines are identified in the spectra. Spectral models produced by exploding a Wolf-Rayet progenitor and injecting a magnetar power source are shown to be qualitatively similar to ASASSN-18km/SN 2018bsz, contrary to most SLSNe-I that display weak or non-existent C (II) lines. ASASSN-18km/SN 2018bsz displays along, slowly rising, red plateau of >26 days, before a steeper, faster rise to maximum. The host has an absolute magnitude of -19.8 mag (r), a mass of M-* = 1.5(-0.33)(+0.08) x 10(9) M-circle dot, and a star formation rate of =0.50(-0.19)(+2.22) M-circle dot yr(-1). A nearby H (II) region has an oxygen abundance (O3N2) of 8.31 +/- 0.01 dex.
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  • Lagrange, A. -M., et al. (author)
  • Post-conjunction detection of beta Pictoris b with VLT/SPHERE
  • 2019
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 621
  • Journal article (peer-reviewed)abstract
    • Context. With an orbital distance comparable to that of Saturn in the solar system, beta Pictoris b is the closest (semi-major axis similar or equal to 9 au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to beta Pictoris have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters.Aims. We aimed at further constraining beta Pictoris b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit.Methods. We used SPHERE at the VLT to precisely monitor the orbital motion of beta beta Pictoris b since first light of the instrument in 2014.Results. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6 au) and prevented further detection. We redetected beta Pictoris b on the northeast side of the disk at a separation of 139 mas and a PA of 30 degrees in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of a = 9.0 +/- 0.5 au (1 sigma), it definitely excludes previously reported possible long orbital periods, and excludes beta Pictoris b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.
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  • Iablonskyi, D., et al. (author)
  • Slow Interatomic Coulombic Decay of Multiply Excited Neon Clusters
  • 2016
  • In: Physical Review Letters. - 0031-9007. ; 117:27
  • Journal article (peer-reviewed)abstract
    • Ne clusters (∼5000 atoms) were resonantly excited (2p→3s) by intense free electron laser (FEL) radiation at FERMI. Such multiply excited clusters can decay nonradiatively via energy exchange between at least two neighboring excited atoms. Benefiting from the precise tunability and narrow bandwidth of seeded FEL radiation, specific sites of the Ne clusters were probed. We found that the relaxation of cluster surface atoms proceeds via a sequence of interatomic or intermolecular Coulombic decay (ICD) processes while ICD of bulk atoms is additionally affected by the surrounding excited medium via inelastic electron scattering. For both cases, cluster excitations relax to atomic states prior to ICD, showing that this kind of ICD is rather slow (picosecond range). Controlling the average number of excitations per cluster via the FEL intensity allows a coarse tuning of the ICD rate.
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  • Zhou, Bin, et al. (author)
  • Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
  • 2016
  • In: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
  • Journal article (peer-reviewed)abstract
    • Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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  • Boström, C., et al. (author)
  • Distribution, structure and function of Nordic eelgrass (Zostera marina) ecosystems: Implications for coastal management and conservation
  • 2014
  • In: Aquatic conservation. - : Wiley. - 1052-7613. ; 24:3, s. 410-434
  • Research review (peer-reviewed)abstract
    • This paper focuses on the marine foundation eelgrass species, Zostera marina, along a gradient from the northern Baltic Sea to the north-east Atlantic. This vast region supports a minimum of 1480km2 eelgrass (maximum >2100km2), which corresponds to more than four times the previously quantified area of eelgrass in Western Europe. Eelgrass meadows in the low salinity Baltic Sea support the highest diversity (4-6 spp.) of angiosperms overall, but eelgrass productivity is low (<2g dw m-2 d-1) and meadows are isolated and genetically impoverished. Higher salinity areas support monospecific meadows, with higher productivity (3-10g dw m-2 d-1) and greater genetic connectivity. The salinity gradient further imposes functional differences in biodiversity and food webs, in particular a decline in number, but increase in biomass of mesograzers in the Baltic. Significant declines in eelgrass depth limits and areal cover are documented, particularly in regions experiencing high human pressure. The failure of eelgrass to re-establish itself in affected areas, despite nutrient reductions and improved water quality, signals complex recovery trajectories and calls for much greater conservation effort to protect existing meadows. The knowledge base for Nordic eelgrass meadows is broad and sufficient to establish monitoring objectives across nine national borders. Nevertheless, ensuring awareness of their vulnerability remains challenging. Given the areal extent of Nordic eelgrass systems and the ecosystem services they provide, it is crucial to further develop incentives for protecting them. © 2014 The Authors.
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  • Tyrrell, Jessica, et al. (author)
  • Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.
  • 2016
  • In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 315:11, s. 1129-40
  • Journal article (peer-reviewed)abstract
    • Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.Offspring birth weight from 18 studies.Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P=.008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P=7×10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P=1×10(-5)), respectively. A 1-SD (≈4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD (≈7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD (≈10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
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  • Beaumont, Robin N, et al. (author)
  • Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
  • 2018
  • In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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  • Clayton, Aled, et al. (author)
  • Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017
  • 2018
  • In: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 7
  • Journal article (other academic/artistic)abstract
    • © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.
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  • Enerbäck, Hanna, et al. (author)
  • Effects of orthodontic treatment and different fluoride regimens on numbers of cariogenic bacteria and caries risk: a randomized controlled trial
  • 2019
  • In: European journal of orthodontics. - : Oxford University Press (OUP). - 1460-2210 .- 0141-5387. ; 41:1, s. 59-66
  • Journal article (peer-reviewed)abstract
    • Background: Caries is an undesirable side-effect of treatment with fixed orthodontic appliances. Therefore, it is crucial to understand how orthodontic treatment and different fluoride regimens affect caries risk and individual risk factors. Objective: To evaluate the effects of orthodontic treatment and different fluoride regimens on caries risk and caries risk factors, including cariogenic bacteria. Trial design: Three-armed, parallel group, randomized, controlled trial. Methods: Patients referred to the Specialist Clinic of Orthodontics, Mölndal Hospital, Sweden, were distributed randomly into the following groups: group I (Control group), 1450 ppm fluoride (F) toothpaste; group II, 1450 ppm F toothpaste plus 0.2 per cent sodium fluoride (NaF) mouth rinse; and group III, 5000 ppm F toothpaste. The inclusion criteria were: age 12-20 years; and bimaxillary treatment with fixed appliances. The primary outcome variables were: caries risk; and the numbers of cariogenic bacteria. Radiographs were taken before treatment to determine the caries status. Data were collected before treatment and after 1 year with a fixed appliance. The variables were compiled into a Cariogram to assess the caries risk. Comparisons were made over time within and between the groups. The generation of randomization sequence was performed in blocks of 30. Blinding was employed during the data analysis and the caries registration. Recruitment: The clinical study duration was from October 2010 to December 2012. Results: Overall, 270 patients were randomized, of which 15 were excluded from the study. Therefore, 255 patients were included in the analyses. The caries risk increased significantly during orthodontic treatment in group I (P < 0.0001), whereas groups II and III had unchanged caries risks. All the groups showed statistically significant increases in the numbers of cariogenic bacteria. Harms: No harms were reported during the trial. Conclusions: To avoid an increased risk of caries during orthodontic treatment, everyday use of high-fluoride toothpaste (5000 ppm F) or mouth rinse (0.2% NaF) in combination with ordinary toothpaste is recommended. Registration: The trial was not registered.
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  • Holmberg, Lars, et al. (author)
  • A comparison of prostate cancer survival in England, Norway and Sweden : A population-based study
  • 2012
  • In: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 36:1, s. e7-e12
  • Journal article (peer-reviewed)abstract
    • Purpose The objective of the study was to compare patterns of survival 2001-2004 in prostate cancer patients from England, Norway and Sweden in relation to age and period of follow-up. Subjects and methods Excess mortality in men with prostate cancer was estimated using nation-wide cancer register data using a period approach for relative survival. 179,112 men in England, 23,192 in Norway and 59,697 in Sweden were included. Results In all age groups, England had the lowest survival, particularly so among men aged 80+. Overall age-standardised five-year survival was 76.4%, 80.3% and 83.0% for England, Norway and Sweden, respectively. The majority of the excess deaths in England were confined to the first year of follow-up. Conclusion The results indicate that a small but important group of older patients present at a late stage and succumb early to their cancers, possibly in combination with severe comorbidity, and this situation is more common in England than in Norway or Sweden.
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  • Moschner, K., et al. (author)
  • Relativistic Coulomb excitation of 88Kr
  • 2016
  • In: Physical Review C - Nuclear Physics. - 0556-2813. ; 94:5
  • Journal article (peer-reviewed)abstract
    • To investigate the systematics of mixed-symmetry states in N=52 isotones, a relativistic Coulomb excitation experiment was performed during the PreSPEC campaign at the GSI Helmholtzzentrum für Schwerionenforschung to determine E2 transition strengths to 2+ states of the radioactive nucleus 88Kr. Absolute transition rates could be measured towards the first and third 2+ states. For the latter a mixed-symmetry character is suggested on the basis of the indication for a strong M1 transition to the fully symmetric 2+1 state, extending the knowledge of the N=52 isotones below Z=40. A comparison with the proton-neutron interacting boson model and shell-model predictions is made and supports the assignment.
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  • Vaugoyeau, Marie, et al. (author)
  • Interspecific variation in the relationship between clutch size, laying date and intensity of urbanization in four species of hole-nesting birds
  • 2016
  • In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 6:16, s. 5907-5920
  • Journal article (peer-reviewed)abstract
    • The increase in size of human populations in urban and agricultural areas has resulted in considerable habitat conversion globally. Such anthropogenic areas have specific environmental characteristics, which influence the physiology, life history, and population dynamics of plants and animals. For example, the date of bud burst is advanced in urban compared to nearby natural areas. In some birds, breeding success is determined by synchrony between timing of breeding and peak food abundance. Pertinently, caterpillars are an important food source for the nestlings of many bird species, and their abundance is influenced by environmental factors such as temperature and date of bud burst. Higher temperatures and advanced date of bud burst in urban areas could advance peak caterpillar abundance and thus affect breeding phenology of birds. In order to test whether laying date advance and clutch sizes decrease with the intensity of urbanization, we analyzed the timing of breeding and clutch size in relation to intensity of urbanization as a measure of human impact in 199 nest box plots across Europe, North Africa, and the Middle East (i.e., the Western Palearctic) for four species of hole-nesters: blue tits (Cyanistes caeruleus), great tits (Parus major), collared flycatchers (Ficedula albicollis), and pied flycatchers (Ficedula hypoleuca). Meanwhile, we estimated the intensity of urbanization as the density of buildings surrounding study plots measured on orthophotographs. For the four study species, the intensity of urbanization was not correlated with laying date. Clutch size in blue and great tits does not seem affected by the intensity of urbanization, while in collared and pied flycatchers it decreased with increasing intensity of urbanization. This is the first large-scale study showing a species-specific major correlation between intensity of urbanization and the ecology of breeding. The underlying mechanisms for the relationships between life history and urbanization remain to be determined. We propose that effects of food abundance or quality, temperature, noise, pollution, or disturbance by humans may on their own or in combination affect laying date and/or clutch size.
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  • Willerslev, E, et al. (author)
  • Fifty thousand years of arctic vegetation change and megafauna diet
  • 2014
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 506:7486, s. 47-47
  • Journal article (peer-reviewed)abstract
    • Although it is generally agreed that the Arctic flora is among the youngest and least diverse on Earth, the processes that shaped it are poorly understood. Here we present 50 thousand years (kyr) of Arctic vegetation history, derived from the first large-scale ancient DNA metabarcoding study of circumpolar plant diversity. For this interval we also explore nematode diversity as a proxy for modelling vegetation cover and soil quality, and diets of herbivorous megafaunal mammals, many of which became extinct around 10 kyr bp (before present). For much of the period investigated, Arctic vegetation consisted of dry steppe-tundra dominated by forbs (non-graminoid herbaceous vascular plants). During the Last Glacial Maximum (25–15 kyr bp), diversity declined markedly, although forbs remained dominant. Much changed after 10 kyr bp, with the appearance of moist tundra dominated by woody plants and graminoids. Our analyses indicate that both graminoids and forbs would have featured in megafaunal diets. As such, our findings question the predominance of a Late Quaternary graminoid-dominated Arctic mammoth steppe.
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  • Bréchignac, Francois, et al. (author)
  • Addressing ecological effects of radiation on populations and ecosystems to improve protection of the environment against radiation : Agreed statements from a Consensus Symposium
  • 2016
  • In: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X .- 1879-1700. ; 158, s. 21-29
  • Research review (peer-reviewed)abstract
    • This paper reports the output of a consensus symposium organized by the International Union of Radioecology in November 2015. The symposium gathered an academically diverse group of 30 scientists to consider the still debated ecological impact of radiation on populations and ecosystems. Stimulated by the Chernobyl and Fukushima disasters' accidental contamination of the environment, there is increasing interest in developing environmental radiation protection frameworks. Scientific research conducted in a variety of laboratory and field settings has improved our knowledge of the effects of ionizing radiation on the environment. However, the results from such studies sometimes appear contradictory and there is disagreement about the implications for risk assessment. The Symposium discussions therefore focused on issues that might lead to different interpretations of the results, such as laboratory versus field approaches, organism versus population and ecosystemic inference strategies, dose estimation approaches and their significance under chronic exposure conditions. The participating scientists, from across the spectrum of disciplines and research areas, extending also beyond the traditional radioecology community, successfully developed a constructive spirit directed at understanding discrepancies. From the discussions, the group has derived seven consensus statements related to environmental protection against radiation, which are supplemented with some recommendations. Each of these statements is contextualized and discussed in view of contributing to the orientation and integration of future research, the results of which should yield better consensus on the ecological impact of radiation and consolidate suitable approaches for efficient radiological protection of the environment.
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  • Claassen, Yvette H. M., et al. (author)
  • Treatment and survival of rectal cancer patients over the age of 80 years : a EURECCA international comparison
  • 2018
  • In: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 119:4, s. 517-522
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+.METHODS: Patients of >= 80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients.RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO.CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.
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  • Claussen, Anetta, et al. (author)
  • Impact of demographics and disease progression on the relationship between glucose and HbA1c
  • 2017
  • In: European Journal of Pharmaceutical Sciences. - : ELSEVIER SCIENCE BV. - 0928-0987 .- 1879-0720. ; 104, s. 417-423
  • Journal article (peer-reviewed)abstract
    • Context: Several studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012).Objective: To assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model.Data: Longitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c. The analysed covariates included age group, HMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component.Participants: Participants included 47% females and 20% above 65 years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races.Analysis: Estimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model.Results: The analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship.Conclusion: Our analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials.
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25.
  • Delerue, N., et al. (author)
  • A Massive Open Online Course on Particle Accelerators
  • 2018. - 9
  • In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1067
  • Conference paper (peer-reviewed)abstract
    • The TIARA (Test Infrastructure and Accelerator Research Area) project funded by the European Union 7th framework programme made a survey of provision of education and training in accelerator science in Europe. This survey highlighted the need for more training opportunities targeting undergraduate-level students. This need is now being addressed by the European Union H2020 project ARIES (Accelerator Research and Innovation for European Science and Society) via the preparation of a Massive Open Online Course (MOOC) on particle accelerator science and engineering. We present here the current status of this project, the main elements of the syllabus, how it will be delivered, and the schedule for providing the course.
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26.
  • Eliasson, Björn, 1959, et al. (author)
  • Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study.
  • 2012
  • In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55:4, s. 915-925
  • Journal article (peer-reviewed)abstract
    • AIMS/HYPOTHESIS: Pharmacological augmentation of glucagon-like peptide 1 receptor signalling by dipeptidyl peptidase 4 (DPP-4) inhibition reduced intestinal lipoprotein secretion in experimental studies, suggesting that DPP-4 inhibitors may ameliorate dyslipidaemia and thus reduce cardiovascular risk in patients with type 2 diabetes. We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal. METHODS: Seventy-one patients (age 18-70years), who did not reach HbA(1c) 6.5% (48mmol/mol) with lifestyle and/or metformin, sulfonylurea or glinide therapy, participated in this 16week, double-centre (university hospitals) Pbo-controlled parallel-group study. All participants, people doing measurements or examinations, and people assessing the outcomes were blinded to group assignment. Fasting TG 1.7-5.0mmol/l was among the entry criteria. Patients received a high-fat mixed meal before and 4 and 16weeks after randomisation (allocation by central office) to Alo (n=25), Alo/Pio (n=22) or Pbo (n=24). Blood was sampled at pre-specified intervals, starting at 15min before and ending 8h after meal ingestion. RESULTS: At week 16, Alo (n=25) and Alo/Pio (n=21) vs Pbo (n=24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p<0.001), as well as in chylomicron TG (p<0.001) and VLDL1 TG iAUCs (p<0.001 and p=0.012, respectively). Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p=0.028), and a non-significant trend towards a decrease with Alo/Pio (p=0.213). The incidence of adverse events was low and consistent with previous studies. CONCLUSIONS/INTERPRETATION: Treatment with Alo and Alo/Pio produced significant reductions in postprandial TG and TG-rich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. The data support the concept that incretins not only modulate glucose metabolism but also influence chylomicron metabolism in intestinal cells. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00655863. FUNDING: The study was funded by Takeda Global Research & Development.
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27.
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28.
  • Eriksson, K, et al. (author)
  • Physical activity in patients with systemic lupus erythematosus and matched controls.
  • 2012
  • In: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 41:4, s. 290-7
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: As physical activity reduces cardiovascular disease (CVD) in the general population, studies concerning the frequency of physical activity in patients with systemic lupus erythematosus (SLE) are needed. Earlier studies indicate that patients with SLE are physically inactive but there are few studies that compare physical activity in SLE to that in the general population. The aim of this study was to examine different aspects of physical activity in patients with SLE and population controls and to investigate how they relate to disease activity and organ damage.METHODS: Two hundred and seventy-two patients with SLE and 272 population controls, individually matched for age, gender, and living region, were investigated clinically. For patients, the investigation included assessment of disease activity using the SLE Disease Activity Index (SLEDAI) and organ damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC) Damage Index. All participants filled out an extensive questionnaire concerning physical activity, exercise capacity, and sedentary behaviour.RESULTS: The mean age of the patients was 47 (SD 15) years. Patients reported lower (p < 0.001) capacity for walking, jogging, and running and more limiting factors for these activities than controls (p < 0.001). Patients exercised less often than controls (p < 0.01) and patients with SLICC ≥ 2 points reported less physical activity on 'low to moderate' intensity compared to their controls (p < 0.05). Sedentary behaviour was reported by 18% of the patients and 26% of the controls (ns).CONCLUSION: Patients with SLE reported lower exercise capacity and less frequent exercise than controls. Additionally, patients with more organ damage reported less physical activity, and these, together with patients who have a sedentary behaviour, should be the focus of intervention programmes to support increased physical activity and exercise in SLE.
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29.
  • Gaedcke, Jochen, et al. (author)
  • The Rectal Cancer microRNAome - microRNA Expression in Rectal Cancer and Matched Normal Mucosa.
  • 2012
  • In: Clinical Cancer Research. - 1078-0432. ; 18:18, s. 4919-4930
  • Journal article (peer-reviewed)abstract
    • PURPOSE: miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We therefore, aimed to comprehensively map the miRNA expression patterns of this disease. EXPERIMENTAL DESIGN: Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa miRNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was validated using semi-quantitative real-time PCR. RESULTS: Forty-nine miRNAs were significantly differentially expressed (log(2)-fold difference >0.5 and P < 0.001) between rectal cancer and normal rectal mucosa. The predicted targets for these miRNAs were enriched for the following pathways: Wnt, TGF-beta, mTOR, insulin, mitogen-activated protein kinase, and ErbB signaling. Thirteen of these 49 miRNAs seem to be rectal cancer-specific, and have not been previously reported for colon cancers: miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p. Of clinical impact, miR-135b expression correlated significantly with disease-free and cancer-specific survival in an independent multicenter cohort of 116 patients. CONCLUSION: This comprehensive analysis of the rectal cancer miRNAome uncovered novel miRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of this disease. Moreover, the identification and validation of miR-135b may help to identify novel molecular targets and pathways for therapeutic exploitation. Clin Cancer Res; 1-12. ©2012 AACR.
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30.
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31.
  • Gorkhover, Tais, et al. (author)
  • Femtosecond X-ray Fourier holography imaging of free-flying nanoparticles
  • 2018
  • In: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 12:3, s. 150-153
  • Journal article (peer-reviewed)abstract
    • Ultrafast X-ray imaging on individual fragile specimens such as aerosols 1 , metastable particles 2 , superfluid quantum systems 3 and live biospecimens 4 provides high-resolution information that is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imaging, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely defined 4,5 . Here, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highest lateral resolution so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond timescale.
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32.
  • Grauers, A, et al. (author)
  • Prevalence of Back Problems in 1069 Adults With Idiopathic Scoliosis and 158 Adults Without Scoliosis.
  • 2014
  • In: Spine. - 1528-1159 .- 0362-2436. ; 39:11, s. 886-892
  • Journal article (peer-reviewed)abstract
    • Study Design. Multi-center case-control studyObjective. To investigate the prevalence of back problems in adults with idiopathic scoliosis.Summary of Background Data. Information on the prevalence of back problems in adults with idiopathic scoliosis is scarce, especially in untreated individuals, males and individuals with an age at onset of the scoliosis of less than 10 years.Methods. 1069 individuals with idiopathic scoliosis and 158 individuals without scoliosis, all aged 20-65 years, answered a questionnaire on back problems. Individuals with scoliosis were diagnosed between ages 4 and 20 years and any treatment was terminated before age 20. Logistic regression or ANCOVA was used for group comparisons.Results. Mean (SD) age at the time of investigation in individuals with scoliosis (123 men and 946 women) was 41 (9) years, and in individuals without scoliosis (75 men and 83 women) 45 (13) years. 374 individuals with scoliosis were untreated, 451 had been brace treated and 244 surgically treated. The mean prevalence of back problems was 64% in the individuals with scoliosis and 29% in the individuals without scoliosis (p<0.001). Among the untreated individuals with scoliosis, 69% reported back problems, among the brace treated 61%, and among the surgically treated 64% (p = 0.06). When comparing females and males with scoliosis, and individuals with juvenile and adolescent scoliosis, there were no statistically significant differences in the prevalence of back problems (p = 0.10 and p = 0.23, respectively).Conclusion. Adults with idiopathic scoliosis have a higher prevalence of back problems than individuals without scoliosis. Treatment, gender and juvenile or adolescent onset of diagnosis was not related to the prevalence of back problems in adulthood.
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33.
  • Gülen, T, et al. (author)
  • Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis.
  • 2017
  • In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 47:7, s. 909-917
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Patients with systemic mastocytosis (SM) have clinical signs of mast cell (MC) activation and increased levels of MC mediators. It is unclear whether the increased mediator levels are caused by increased numbers of tissue MCs, or whether these cells in affected individuals have a hyperactive phenotype.OBJECTIVE: To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with SM.METHODS: were measured, as well as ex vivo basophil histamine release.RESULTS: Mast cell mediators in the blood and urine were significantly higher in patients with SM than in HC and A controls. Responsiveness to local activation of skin MCs (by morphine) and airway MCs (by mannitol) was similar in SM and HC groups. Likewise, end-organ responsiveness in the skin to histamine, and in the airways to methacholine, was similar in all three subject groups. There was no evidence of increased basophil reactivity in SM patients.CONCLUSIONS AND CLINICAL RELEVANCE: Mast cells in the skin and airways of subjects with SM do not exhibit hyper-reactivity towards the MC-activating stimuli morphine and mannitol, respectively. Therefore, the highly elevated baseline levels of MC mediators in SM are most likely due to increased MC numbers, rather than altered MC responsiveness. The underlying mechanisms could involve leakage of MC mediators, or dysfunctions in mediator synthesis, storage and release. One clinical implication of our study is that there is no contraindication to perform skin tests using morphine in subjects with mastocytosis.
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34.
  • Hartoog, O. E., et al. (author)
  • VLT/X-Shooter spectroscopy of the afterglow of the Swift GRB 130606A Chemical abundances and reionisation at z similar to 6
  • 2015
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
  • Journal article (peer-reviewed)abstract
    • Context: The reionisation of the Universe is a process that is thought to have ended around z similar to 6, as inferred from spectroscopy of distant bright background sources, such as quasars (QSO) and gamma-ray burst (GRB) afterglows. Furthermore, spectroscopy of a GRB afterglow provides insight in its host galaxy, which is often too dim and distant to study otherwise.Aims: For the Swift GRB 130606A at z = 5.913 we have obtained a high S/N spectrum covering the full optical and near-IR wavelength region at intermediate spectral resolution with VLT/X-Shooter. We aim to measure the degree of ionisation of the intergalactic medium (IGM) between z = 5.02-5.84 and to study the chemical abundance pattern and dust content of its host galaxy.Methods: We estimated the UV continuum of the GRB afterglow using a power-law extrapolation, then measured the flux decrement due to absorption at Ly alpha,beta, and gamma wavelength regions. Furthermore, we fitted the shape of the red damping wing of Lya. The hydrogen and metal absorption lines formed in the host galaxy were fitted with Voigt profiles to obtain column densities. We investigated whether ionisation corrections needed to be applied.Results: Our measurements of the Ly alpha-forest optical depth are consistent with previous measurements of QSOs, but have a much smaller uncertainty. The analysis of the red damping wing yields a neutral fraction x(HI) < 0.05 (3 sigma). We obtain column density measurements of H, Al, Si, and Fe; for C, O, S and Ni we obtain limits. The ionisation due to the GRB is estimated to be negligible (corrections < 0.03 dex), but larger corrections may apply due to the pre-existing radiation field (up to 0.4 dex based on sub-DLA studies). Assuming that [Si/Fe] = +0.79 +/- 0.13 is due to dust depletion, the dust-to-metal ratio is similar to the Galactic value.Conclusions: Our measurements confirm that the Universe is already predominantly ionised over the redshift range probed in this work, but was slightly more neutral at z > 5.6. GRBs are useful probes of the ionisation state of the IGM in the early Universe, but because of internal scatter we need a larger statistical sample to draw robust conclusions. The high [Si/Fe] in the host can be due to dust depletion, a-element enhancement, or a combination of both. The very high value of [Al/Fe] = 2.40 +/- 0.78 might be due to a proton capture process and is probably connected to the stellar population history. We estimate the host metallicity to be -1.7 < [M/H] < -0.9 (2%-13% of solar).
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35.
  • Hasan, A, et al. (author)
  • World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia : Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.
  • 2012
  • In: The World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 13:5, s. 318-378
  • Journal article (peer-reviewed)abstract
    • These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A–F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.
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36.
  • Heinrich, Benjamin C., et al. (author)
  • Local Stability of High Order Power Control in Cellular Networks
  • 2011
  • In: 2011 50th IEEE Conference on Decision and Control and European Control Conference. - 9781612848013 ; , s. 4528-4534
  • Conference paper (peer-reviewed)abstract
    • We address three major control challenges present in power control of wireless cellular networks: time-delays, interference and the binary control feedback. The power control is distributed and based on measurements of the Signal-to-Interference Ratio (SIR). This implies that the users are coupled through the mutual interference.In this paper we show that the interference feedback plays a fundamental role for system stability and behavior. The interference is captured by the so-called feasibility matrix, which contains the interference couplings weighted with SIR-requirements. First, we consider a simplified system and derive a Nyquist stability criterion which separates the system dynamics from the eigenvalues of the feasibility matrix. This criterion is also used to derive bounds on the rate of convergence. Second, we investigate oscillations caused by the binary feedback using harmonic balance techniques. Here, we obtain a similar separation result. Using the structure of the feasibility matrix we derive bounds on the eigenvalue location, which can be seen as a robustness result to disturbances. In an example we illustrate the stability results and predict and observe oscillation modes that are caused by the interference feedback.
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37.
  • Hjort, Line, et al. (author)
  • FOETAL for NCD-FOetal Exposure and Epidemiological Transitions : the role of Anaemia in early Life for Non-Communicable Diseases in later life: a prospective preconception study in rural Tanzania
  • 2019
  • In: BMJ Open. - : BMJ. - 2044-6055. ; 9:5
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Low-income and middle-income countries such as Tanzania experience a high prevalence of non-communicable diseases (NCDs), including anaemia. Studying if and how anaemia affects growth, placenta development, epigenetic patterns and newborns' risk of NCDs may provide approaches to prevent NCDs.PARTICIPANTS: The FOETALforNCD (FOetal Exposure and Epidemiological Transitions: the role of Anaemia in early Life for Non-Communicable Diseases in later life) Study is a population-based preconception, pregnancy and birth cohort study (n=1415, n=538, n=427, respectively), conducted in a rural region of North-East Tanzania. All participants were recruited prior to conception or early in pregnancy and followed throughout pregnancy as well as at birth. Data collection included: maternal blood, screening for NCDs and malaria, ultrasound in each trimester, neonatal anthropometry at birth and at 1 month of age, cord blood, placental and cord biopsies for stereology and epigenetic analyses.FINDINGS TO DATE: At preconception, the average age, body mass index and blood pressure of the women were 28 years, 23 kg/m2 and 117/75 mm Hg, respectively. In total, 458 (36.7%) women had anaemia (haemoglobin Hb <12 g/dL) and 34 (3.6%) women were HIV-positive at preconception. During pregnancy 359 (66.7%) women had anaemia of which 85 (15.8%) women had moderate-to-severe anaemia (Hb ≤9 g/dL) and 33 (6.1%) women had severe anaemia (Hb ≤8 g/dL). In total, 185 (34.4%) women were diagnosed with malaria during pregnancy.FUTURE PLANS: The project will provide new knowledge on how health, even before conception, might modify the risk of developing NCDs and how to promote better health during pregnancy. The present project ended data collection 1 month after giving birth, but follow-up is continuing through regular monitoring of growth and development and health events according to the National Road Map Strategic Plan in Tanzania. This data will link fetal adverse event to childhood development, and depending on further grant allocation, through a life course follow-up.
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38.
  • Horikoshi, Momoko, et al. (author)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
  • Journal article (peer-reviewed)abstract
    • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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39.
  • Jaspers, C., et al. (author)
  • Reproduction rates under variable food conditions and starvation in Mnemiopsis leidyi: significance for the invasion success of a ctenophore
  • 2015
  • In: Journal of Plankton Research. - : Oxford University Press (OUP). - 0142-7873 .- 1464-3774. ; 37:5, s. 1011-1018
  • Journal article (peer-reviewed)abstract
    • The ctenophore Mnemiopsis leidyi is characterized by high growth rates and a large reproductive capacity. However, reproductive dynamics are not yet well understood. Here, we present laboratory data on food-dependent egg production in M. leidyi and egg hatching time and success. Further, we report on the reproduction of laboratory-reared and field-caught animals during starvation. Our results show that the half-saturation zooplankton prey concentration for egg production is reached at food levels of 12-23 mu gC L-1, which is below the average summer food concentration encountered in invaded areas of northern Europe. Furthermore, starved animals continue to produce eggs for up to 12 days after cessation of feeding with high overall hatching success of 65-90%. These life history traits allow M. leidyi to thrive and reproduce in environments with varying food conditions and give it a competitive advantage under unfavourable conditions. This may explain why recurrent population blooms are observed and sustained in localized areas in invaded northern Europe, where water exchange is limited and zooplankton food resources are quickly depleted by M. leidyi. We suggest that these reproductive life history traits are key to its invasion success.
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40.
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41.
  • Jørgensen, Tine, et al. (author)
  • A comparative study of ancient sedimentary DNA, pollen and macrofossils from permafrost sediments of Northern Siberia reveals long-term vegetational stability
  • 2012
  • In: Molecular Ecology. - 0962-1083. ; 21:8, s. 1989-2003
  • Journal article (peer-reviewed)abstract
    • Abstract in Undetermined Although ancient DNA from sediments (sedaDNA) has been used to investigate past ecosystems, the approach has never been directly compared with the traditional methods of pollen and macrofossil analysis. We conducted a comparative survey of 18 ancient permafrost samples spanning the Late Pleistocene (4612.5 thousand years ago), from the Taymyr Peninsula in northern Siberia. The results show that pollen, macrofossils and sedaDNA are complementary rather than overlapping and, in combination, reveal more detailed information on plant palaeocommunities than can be achieved by each individual approach. SedaDNA and macrofossils share greater overlap in plant identifications than with pollen, suggesting that sedaDNA is local in origin. These two proxies also permit identification to lower taxonomic levels than pollen, enabling investigation into temporal changes in species composition and the determination of indicator species to describe environmental changes. Combining data from all three proxies reveals an area continually dominated by a mosaic vegetation of tundra-steppe, pioneer and wet-indicator plants. Such vegetational stability is unexpected, given the severe climate changes taking place in the Northern Hemisphere during this time, with changes in average annual temperatures of >22 degrees C. This may explain the abundance of ice-age mammals such as horse and bison in Taymyr Peninsula during the Pleistocene and why it acted as a refugium for the last mainland woolly mammoth. Our finding reveals the benefits of combining sedaDNA, pollen and macrofossil for palaeovegetational reconstruction and adds to the increasing evidence suggesting large areas of the Northern Hemisphere remained ecologically stable during the Late Pleistocene.
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42.
  • Kirsebom, O. S., et al. (author)
  • Discovery of an Exceptionally Strong β -Decay Transition of F 20 and Implications for the Fate of Intermediate-Mass Stars
  • 2019
  • In: Physical Review Letters. - 0031-9007. ; 123:26
  • Journal article (peer-reviewed)abstract
    • A significant fraction of stars between 7 and 11 solar masses are thought to become supernovae, but the explosion mechanism is unclear. The answer depends critically on the rate of electron capture on Ne20 in the degenerate oxygen-neon stellar core. However, because of the unknown strength of the transition between the ground states of Ne20 and F20, it has not previously been possible to fully constrain the rate. By measuring the transition, we establish that its strength is exceptionally large and that it enhances the capture rate by several orders of magnitude. This has a decisive impact on the evolution of the core, increasing the likelihood that the star is (partially) disrupted by a thermonuclear explosion rather than collapsing to form a neutron star. Importantly, our measurement resolves the last remaining nuclear physics uncertainty in the final evolution of degenerate oxygen-neon stellar cores, allowing future studies to address the critical role of convection, which at present is poorly understood
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43.
  • Kjær, Kasper S., et al. (author)
  • Finding intersections between electronic excited state potential energy surfaces with simultaneous ultrafast X-ray scattering and spectroscopy
  • 2019
  • In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 10:22, s. 5749-5760
  • Journal article (peer-reviewed)abstract
    • Light-driven molecular reactions are dictated by the excited state potential energy landscape, depending critically on the location of conical intersections and intersystem crossing points between potential surfaces where non-adiabatic effects govern transition probabilities between distinct electronic states. While ultrafast studies have provided significant insight into electronic excited state reaction dynamics, experimental approaches for identifying and characterizing intersections and seams between electronic states remain highly system dependent. Here we show that for 3d transition metal systems simultaneously recorded X-ray diffuse scattering and X-ray emission spectroscopy at sub-70 femtosecond time-resolution provide a solid experimental foundation for determining the mechanistic details of excited state reactions. In modeling the mechanistic information retrieved from such experiments, it becomes possible to identify the dominant trajectory followed during the excited state cascade and to determine the relevant loci of intersections between states. We illustrate our approach by explicitly mapping parts of the potential energy landscape dictating the light driven low-to-high spin-state transition (spin crossover) of [Fe(2,2′-bipyridine)3]2+, where the strongly coupled nuclear and electronic dynamics have been a source of interest and controversy. We anticipate that simultaneous X-ray diffuse scattering and X-ray emission spectroscopy will provide a valuable approach for mapping the reactive trajectories of light-triggered molecular systems involving 3d transition metals.
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44.
  • Lambert, Paul C, et al. (author)
  • Quantifying differences in breast cancer survival between England and Norway
  • 2011
  • In: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 35:6, s. 526-533
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Survival from breast cancer is lower in the UK than in some other European countries. We compared survival in England and Norway by age and time from diagnosis. METHODS: We included 303,648 English and 24,919 Norwegian cases of breast cancer diagnosed 1996-2004 using flexible parametric relative survival models, enabling improved quantification of differences in survival. Crude probabilities were estimated to partition the probability of death due to all causes into that due to cancer and other causes and to estimate the number of "avoidable" deaths. RESULTS: England had lower relative survival for all ages with the difference increasing with age. Much of the difference was due to higher excess mortality in England in the first few months after diagnosis. Older patients had a higher proportion of deaths due to other causes. At 5 years post diagnosis, a woman aged 85 in England had probabilities of 0.35 of dying of cancer and 0.32 of dying of other causes, whilst in Norway they were 0.26 and 0.35. By eight years the number of "avoidable" all-cause deaths in England was 1020 with the number of "avoidable" breast cancer related deaths 1488. CONCLUSION: Lower breast cancer survival in England is mainly due to higher mortality in the first year after diagnosis. Crude probabilities aid our understanding of the impact of disease on individual patients and help assess different treatment options.
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45.
  •  
46.
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47.
  • Mattsson, Malin, et al. (author)
  • Uncertainty and opportunities in patients with established eystemic Lupus Erythematosus : A qualitative study
  • 2012
  • In: Musculoskeletal Care. - : Wiley. - 1478-2189 .- 1557-0681. ; 10:1, s. 1-12
  • Journal article (peer-reviewed)abstract
    • Systemic lupus erythematosus (SLE) is a chronic disease which can affect any organ, and the impact of the condition will affect each person differently. There are few qualitative studies including the experiences of both women and men with a diagnosis of SLE corresponding to the American College of Rheumatology (ACR) criteria where both negative and positive impacts of the disease have been presented. Purpose: The aim was to describe how patients with established SLE experience their illness in everyday life, including both negative and positive aspects. Method: Four focus group interviews were conducted with 16 women and three men with SLE according to ACR criteria, with varied disease activity and no or little organ damage. The interviews were tape recorded, transcribed verbatim and analysed using qualitative content analysis. Results: Two themes emerged: multifaceted uncertainty contained the categories 'an unreliable body', 'obtrusive pain and incomprehensible fatigue', 'mood changes and worries', 'reliance on medication and health care'; Focus on health and opportunities included 'learning process implying personal strength', 'limitations and possibilities in activities and work', 'a challenge to explain and receive support' and 'living an ordinary life incorporating meaningful occupations'. Conclusions: While we expected to find a mainly negative impact, positive aspects were also described. Our findings were complex and showed that patients with established SLE can experience both uncertainty and opportunities. This highlights the importance for healthcare professionals of gaining a better understanding of patients' uncertainty, to enable them to support patients, allowing them to focus on health and opportunities. Measurement instruments that capture different aspects of uncertainty and opportunities needs to be developed.
  •  
48.
  • Møller, Henrik, et al. (author)
  • Colorectal cancer survival in socioeconomic groups in England : Variation is mainly in the short term after diagnosis
  • 2012
  • In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:1, s. 46-53
  • Journal article (peer-reviewed)abstract
    • The objective of this study was to examine differences in cancer survival between socioeconomic groups in England, with particular attention to survival in the short term of follow-up. PATIENTS AND METHODS: Individuals diagnosed with colorectal cancer between 1996 and 2004 in England were identified from cancer registry records. Five-year cumulative relative survival and excess death rates were computed. RESULTS: For colon cancer there was a very high excess death rate in the first month of follow-up, and the excess death rate was highest in the socioeconomically deprived groups. In subsequent periods, excess mortality rates were much lower and there was less socioeconomic variation. The pattern of variation in excess death rates was generally similar in rectal cancer but the socioeconomic difference in death rates persisted several years longer. If the excess death rates in the entire colorectal cancer patient population were the same as those observed in the most affluent socioeconomic quintile, the annual reduction would be 360 deaths in colon cancer and 336 deaths in rectal cancer patients. These deaths occurred almost entirely in the first month and the first year after diagnosis. CONCLUSION: Recent developments in the national cancer control agenda have included an increasing emphasis on outcome measures, with short-term cancer survival an operational measure of variation and progress in cancer control. In providing clues to the nature of the survival differences between socioeconomic groups, the results presented here give strong support for this strategy.
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49.
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50.
  • Møller, J B, et al. (author)
  • Longitudinal Modeling of the Relationship Between Mean Plasma Glucose and HbA1c Following Antidiabetic Treatments
  • 2013
  • In: CPT. - : Wiley. - 2163-8306. ; 2, s. e82-
  • Journal article (peer-reviewed)abstract
    • Late-phase clinical trials within diabetes generally have a duration of 12-24 weeks, where 12 weeks may be too short to reach steady-state glycated hemoglobin (HbA1c). The main determinant for HbA1c is blood glucose, which reaches steady state much sooner. In spite of this, few publications have used individual data to assess the time course of both glucose and HbA1c, for predicting HbA1c. In this paper, we present an approach for predicting HbA1c at end-of-trial (24-28 weeks) using glucose and HbA1c measurements up to 12 weeks. The approach was evaluated using data from 4 trials covering 12 treatment arms (oral antidiabetic drug, glucagon-like peptide-1, and insulin treatment) with measurements at 24-28 weeks to evaluate predictions vs. observations. HbA1c percentage was predicted for each arm at end-of-trial with a mean prediction error of 0.14% [0.01;0.24]. Furthermore, end points in terms of HbA1c reductions relative to comparator were accurately predicted. The proposed model provides a good basis to optimize late-stage clinical development within diabetes.
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