Multi-fluid modelling of idealized convection

Atmospheric convection is hugely important for weather and climate prediction, but parametrizations of the process in weather and climate models often behave poorly. Traditional parametrization assumptions break down at resolutions comparable to the dominant energy-containing structures. Lack of understanding of this convective “grey zone” is one of the biggest barriers to improving our representation of convection. The grey zone is a concept that applies to any turbulent flow — dry or moist. Therefore this thesis focuses on the simplest convection problem: Rayleigh-B´enard convection (RBC). It is shown that RBC possesses remarkably similar grey zone behaviour to that observed in numerical weather prediction models. In convection, large portions of the turbulent fluxes are carried by coherent structures. This motivates the split into “convection” and “environment” underlying traditional mass flux schemes, which can be generalized via conditional filtering. Introducing explicit discontinuous fluid relabelling terms leads to a multi-fluid equation set that is more complete than those currently published. New expressions for resolved relabelling terms are derived, and an argument is presented linking pressure differences between fluids to an isotropic stress introduced by relabelling. To show the validity of the multi-fluid approach, a 1D, time-dependent model of RBC is developed. The model has one rising and one falling fluid, and assumes that this split captures all subfilter variability. A scaling argument for the pressure differences between fluids reduces the free parameters to two O(1) constants. After determining these constants, correct scalings of the domain-averaged heat and momentum fluxes are predicted over six decades of buoyancy forcing. Thus even a simple two-fluid model can capture the essentials of convection. In 2D, the same model formulation improves initiation of convection across the grey zone, and reduces sensitivity of heat and momentum fluxes to grid spacing, compared to a single-fluid model with constant viscosity. It is shown that the closures successful in a single column do not provide sufficient constraint to maintain the correct sign of vertical velocity in the grey zone. The need for better understanding of the relabelling terms and their resolution-dependence emerges as the key barrier to progress

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Taxonomic, phylogenetic, and environmental trade-offs between leaf productivity and persistence

Assessing the influence of climate, soil fertility, and species identity on leaf trait relationships is crucial for understanding the adaptations of plants to their environment and for interpreting leaf trait relationships across spatial scales. In a comparative field study of 171 plant species in 174 grassland sites across China, we examined the trade-offs, defined as negative covariance between two traits, between leaf persistence (leaf mass per area, LMA) and leaf productivity (mass-based photosynthetic rate, Amass, N and P content, and photosynthetic N use efficiency, PNUE). We asked to which extent these trade-offs were influenced by: (1) variation among sites within species, decomposed into variation due to climatic and soil variables; (2) variation among species within sites, decomposed into variation among taxonomic, functional, or phylogenetic groups; and (3) the joint contribution of variation among species and sites. We used mixed-model analysis of covariance to partition bivariate relationships between leaf traits into trade-off components. We found significant mass-based persistence–productivity trade-offs of LMA–Amass, LMA–N, LMA–P, and LMA– PNUE consistent with previous broadscale findings. Overall, (1) variation among sites within species explained 14–23%, (2) variation among species within sites explained 20–34%, and (3) the two together explained 42–63% of the total covariance between leaf traits. Interspecific trade-offs of LMA–Amass, LMA–N, and LMA–P were stronger than inter-site ones. A relatively low amount of covariance was explained by climatic and soil variables. However, we found the trade-offs were stronger for LMA–N and LMA–P at higher precipitation and for LMA–PNUE at greater soil fertility, if displayed by major axis regression, which combined both intra- and interspecific variation. Residual trade-offs within species and sites were weak, suggesting that intraspecific, intra-site variation in physiology was less important than variation imposed by species identity or environmental differences among sites. Our results from grassland biomes add evidence for the fundamental nature of productivity–persistence trade-offs in plants. No individual factor emerged as the single major cause for these tradeoffs. Rather, the total covariance between leaf traits was explained by a combination of factors, each contributing a range of explanatory power

Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome

We previously demonstrated that constitutional BUB1B mutations cause mosaic variegated aneuploidy, a condition characterized by constitutional aneuploidies and childhood cancer predisposition. To further investigate the role of BUB1B in cancer predisposition we performed comparative genomic hybridization analysis in an embryonal rhabdomyosarcoma from an MVA case with biallelic BUB1B mutations, revealing aneuploidies typical of sporadic E-RMS, with gain of chromosomes 3, 8, 13 and loss of chromosomes 9, 14, X. To investigate whether somatic BUB1B mutations occur in sporadic childhood cancers we screened 30 Wilms tumours, 10 acute lymphoblastic leukemias, nine rhabdomyosarcomas and 11 rhabdomyosarcoma cell lines for BUB1B mutations. We identified seven exonic and six intronic variants. Six of the exonic variants were synonymous and one resulted in a non-synonymous conservative missense alteration that was also present in a control. These data suggest that the genetic progression in rhabdomyosarcoma from MVA and non-MVA cases may be similar, but that somatic BUB1B mutations are unlikely to be common in sporadic childhood cancers known to be associated with MVA

Association between large-scale genomic homozygosity without chromosomal loss and nonseminomatous germ cell tumor development

The genotype of a tumor determines its biology and clinical behavior. The genetic alterations associated with the unique embryonal morphology of nonseminomatous subtypes of testicular germ cell tumors remain to be established. Using single nucleotide polymorphism microarray analysis, we found in all of the 15 nonseminomas analyzed, large-scale chromosomal homozygosities, most of which were not associated with relative chromosome loss. This unusual genotype, distinguishing nonseminoma from seminomas and other human tumors, may be associated with the special embryonal development morphologic transition of this malignancy. Based on these genetic data, we hypothesized a new potential origin of nonseminomas through sperm fusion. Nonrandom involvement of certain chromosomes also suggests that genes on these chromosome regions may play an important role in nonseminoma development

PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification.

PURPOSE: To improve the risk stratification of patients with rhabdomyosarcoma (RMS) through the use of clinical and molecular biologic data. PATIENTS AND METHODS: Two independent data sets of gene-expression profiling for 124 and 101 patients with RMS were used to derive prognostic gene signatures by using a meta-analysis. These and a previously published metagene signature were evaluated by using cross validation analyses. A combined clinical and molecular risk-stratification scheme that incorporated the PAX3/FOXO1 fusion gene status was derived from 287 patients with RMS and evaluated. RESULTS: We showed that our prognostic gene-expression signature and the one previously published performed well with reproducible and significant effects. However, their effect was reduced when cross validated or tested in independent data and did not add new prognostic information over the fusion gene status, which is simpler to assay. Among nonmetastatic patients, patients who were PAX3/FOXO1 positive had a significantly poorer outcome compared with both alveolar-negative and PAX7/FOXO1-positive patients. Furthermore, a new clinicomolecular risk score that incorporated fusion gene status (negative and PAX3/FOXO1 and PAX7/FOXO1 positive), Intergroup Rhabdomyosarcoma Study TNM stage, and age showed a significant increase in performance over the current risk-stratification scheme. CONCLUSION: Gene signatures can improve current stratification of patients with RMS but will require complex assays to be developed and extensive validation before clinical application. A significant majority of their prognostic value was encapsulated by the fusion gene status. A continuous risk score derived from the combination of clinical parameters with the presence or absence of PAX3/FOXO1 represents a robust approach to improving current risk-adapted therapy for RMS