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To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). 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(2). In an expanded genome-wide association metaanalysis 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.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
Exploring, exploiting and evolving diversity of aquatic ecosystem models: a community perspective
(2015)
Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly available through open-source policies, to standardize documentation and technical implementation of models, and to compare models through ensemble modelling and interdisciplinary approaches. We end with our perspective on how the field of aquatic ecosystem modelling might develop in the next 5-10 years. To strive for clarity and to improve readability for non-modellers, we include a glossary.
During the Ring Grazing orbits near the end of Cassini mission, the spacecraft crossed the equatorial plane near the orbit of Janus/Epimetheus (similar to 2.5 Rs). This region is populated with dust particles that can be detected by the Radio and Plasma Wave Science (RPWS) instrument via an electric field antenna signal. Analysis of the voltage waveforms recorded on the RPWS antennas provides estimations of the density and size distribution of the dust particles. Measured RPWS profiles, fitted with Lorentzian functions, are shown to be mostly consistent with the Cosmic Dust Analyzer, the dedicated dust instrument on board Cassini. The thickness of the dusty ring varies between 600 and 1,000 km. The peak location shifts north and south within 100 km of the ring plane, likely a function of the precession phase of Janus orbit.
Plain Language Summary Cassini flew through the gap between Saturn and its rings for 22 times before plunging into the atmosphere of Saturn, ending its 20-year mission. The radio and plasma waves instrument on board Cassini helped quantify the dust hazard in this previously unexplored region. The measured density of large dust particles was much lower than expected, allowing high-value science observations during the subsequent Grand Finale orbits.
A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and traitbased models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem models.
A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and traitbased models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem models.
Recent global warming is acting across marine, freshwater, and terrestrial ecosystems to favor species adapted to warmer conditions and/or reduce the abundance of cold-adapted organisms (i.e., "thermophilization" of communities). Lack of community responses to increased temperature, however, has also been reported for several taxa and regions, suggesting that "climatic lags" may be frequent. Here we show that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag. Using data from 1,409 vegetation plots in European and North American temperate forests, each surveyed at least twice over an interval of 12-67 y, we document significant thermophilization of ground-layer plant communities. These changes reflect concurrent declines in species adapted to cooler conditions and increases in species adapted to warmer conditions. However, thermophilization, particularly the increase of warm-adapted species, is attenuated in forests whose canopies have become denser, probably reflecting cooler growing-season ground temperatures via increased shading. As standing stocks of trees have increased in many temperate forests in recent decades, local microclimatic effects may commonly be moderating the impacts of macroclimate warming on forest understories. Conversely, increases in harvesting woody biomass-e.g., for bioenergy-may open forest canopies and accelerate thermophilization of temperate forest biodiversity.
Steuern und Abgaben auf Produkte oder Verbrauch mit gesellschaftlichen Folgekosten (externe Kosten) – sogenannte Pigou- oder Lenkungssteuern – sind ein gesellschaftliches „Win-Win-Instrument“. Sie verbessern die Wohlfahrt und schützen gleichzeitig die Umwelt und das Klima. Dies wird erreicht, indem umweltschädigende Aktivitäten einen Preis bekommen, der möglichst exakt der Höhe des Schadens entspricht. Eine konsequente Bepreisung der externen Kosten nach diesem Prinzip könnte in Deutschland erhebliche zusätzliche Einnahmen erbringen: Basierend auf bisherigen Studien zu externen Kosten wären zusätzliche Einnahmen in der Größenordnung von 348 bis 564 Milliarden Euro pro Jahr (44 bis 71 Prozent der gesamten Steuereinnahmen) möglich. Die Autoren warnen allerdings, dass die Bezifferung der externen Kosten mit erheblichen Unsicherheiten verbunden ist. Damit Lenkungssteuern und -abgaben ihre positiven Lenkungs- und Wohlstandseffekte voll entfalten können, seien zudem institutionelle Reformen notwendig.
This paper introduces the project on 'Assessing the impact of land use change on hydrology by ensemble modeling (LUCHEM)' that aims at investigating the envelope of predictions on changes in hydrological fluxes due to land use change. As part of a series of four papers, this paper outlines the motivation and setup of LUCHEM, and presents a model intercomparison for the present-day simulation results. Such an intercomparison provides a valuable basis to investigate the effects of different model structures on model predictions and paves the ground for the analysis of the performance of multi-model ensembles and the reliability of the scenario predictions in companion papers. in this study, we applied a set of 10 lumped, semi-lumped and fully distributed hydrological models that have been previously used in land use change studies to the low mountainous Dill catchment. Germany. Substantial differences in model performance were observed with Nash-Sutcliffe efficiencies ranging from 0.53 to 0.92. Differences in model performance were attributed to (1) model input data, (2) model calibration and (3) the physical basis of the models. The models were applied with two sets of input data: an original and a homogenized data set. This homogenization of precipitation, temperature and leaf area index was performed to reduce the variation between the models. Homogenization improved the comparability of model simulations and resulted in a reduced average bias, although some variation in model data input remained. The effect of the physical differences between models on the long-term water balance was mainly attributed to differences in how models represent evapotranspiration. Semi-lumped and lumped conceptual models slightly outperformed the fully distributed and physically based models. This was attributed to the automatic model calibration typically used for this type of models. Overall, however, we conclude that there was no superior model if several measures of model performance are considered and that all models are suitable to participate in further multi-model ensemble set-ups and land use change scenario investigations.
An ensemble of 10 hydrological models was applied to the same set of land use change scenarios. There was general agreement about the direction of changes in the mean annual discharge and 90% discharge percentile predicted by the ensemble members, although a considerable range in the magnitude of predictions for the scenarios and catchments under consideration was obvious. Differences in the magnitude of the increase were attributed to the different mean annual actual evapotranspiration rates for each land use type. The ensemble of model runs was further analyzed with deterministic and probabilistic ensemble methods. The deterministic ensemble method based on a trimmed mean resulted in a single somewhat more reliable scenario prediction. The probabilistic reliability ensemble averaging (REA) method allowed a quantification of the model structure uncertainty in the scenario predictions. It was concluded that the use of a model ensemble has greatly increased our confidence in the reliability of the model predictions.
This paper reports on a project to compare predictions from a range of catchment models applied to a mesoscale river basin in central Germany and to assess various ensemble predictions of catchment streamflow. The models encompass a large range in inherent complexity and input requirements. In approximate order of decreasing complexity, they are DHSVM, MIKE-SHE, TOPLATS, WASIM-ETH, SWAT, PRMS, SLURP, HBV, LASCAM and IHACRES. The models are calibrated twice using different sets of input data. The two predictions from each model are then combined by simple averaging to produce a single-model ensemble. The 10 resulting single-model ensembles are combined in various ways to produce multi-model ensemble predictions. Both the single-model ensembles and the multi-model ensembles are shown to give predictions that are generally superior to those of their respective constituent models, both during a 7-year calibration period and a 9- year validation period. This occurs despite a considerable disparity in performance of the individual models. Even the weakest of models is shown to contribute useful information to the ensembles they are part of. The best model combination methods are a trimmed mean (constructed using the central four or six predictions each day) and a weighted mean ensemble (with weights calculated from calibration performance) that places relatively large weights on the better performing models. Conditional ensembles. in which separate model weights are used in different system states (e.g. summer and winter, high and low flows) generally yield little improvement over the weighted mean ensemble. However a conditional ensemble that discriminates between rising and receding flows shows moderate improvement. An analysis of ensemble predictions shows that the best ensembles are not necessarily those containing the best individual models. Conversely, it appears that some models that predict well individually do not necessarily combine well with other models in multi-model ensembles. The reasons behind these observations may relate to the effects of the weighting schemes, non- stationarity of the climate series and possible cross-correlations between models.
Recent technological developments have increased the number of variables being monitored in lakes and reservoirs using automatic high frequency monitoring (AHFM). However, design of AHFM systems and posterior data handling and interpretation are currently being developed on a site-by-site and issue-by-issue basis with minimal standardization of protocols or knowledge sharing. As a result, many deployments become short-lived or underutilized, and many new scientific developments that are potentially useful for water management and environmental legislation remain underexplored. This Critical Review bridges scientific uses of AHFM with their applications by providing an overview of the current AHFM capabilities, together with examples of successful applications. We review the use of AHFM for maximizing the provision of ecosystem services supplied, by lakes and reservoirs (consumptive and non consumptive uses, food production, and recreation), and for reporting lake status in the EU Water Framework Directive. We also highlight critical issues to enhance the application of AHFM, and suggest the establishment of appropriate networks to facilitate knowledge sharing and technological transfer between potential users. Finally, we give advice on how modern sensor technology can successfully be applied on a larger scale to the management of lakes and reservoirs and maximize the ecosystem services they provide.