A pragmatic benchmarking study of an evidence-based personalised approach in 1938 adolescents with high-risk idiopathic scoliosis

Combining evidence-based medicine and shared decision making, current guidelines support an evidence-based personalised approach (EBPA) for idiopathic scoliosis in adolescents (AIS). EBPA is considered important for adolescents\u2019 compliance, which is particularly difficult in AIS. Benchmarking to existing Randomised Controlled Trials (RCTs) as paradigms of single treatments, we aimed to check the effectiveness and burden of care of an EBPA in high-risk AIS. This study\u2019s design features a retrospective observation of a prospective database including 25,361 spinal deformity patients < 18 years of age. Participants consisted of 1938 AIS, 11\u201345\u25e6 Cobb, Risser stage 0\u20132, who were studied until the end of growth. EBPA included therapies classified for burdensomeness according to current guidelines. Using the same inclusion criteria of the RCTs on exercises, plastic, and elastic bracing, out of the 1938 included, we benchmarked 590, 687, and 884 participants, respectively. We checked clinically significant results and burden of care, calculating Relative Risk of success (RR) and Number Needed to Treat (NNT) for efficacy (EA) and intent-to-treat analyses. At the end of growth, 19% of EBPA participants progressed, while 33% improved. EBPA showed 2.0 (1.7\u20132.5) and 2.9 (1.7\u20134.9) RR of success versus Weinstein and Coillard\u2019s studies control groups, respectively. Benchmarked to plastic or elastic bracing, EBPA had 1.4 (1.2\u20131.5) and 1.7 (1.2\u20132.5) RR of success, respectively. The EBPA treatment burden was greater than RCTs in 48% of patients, and reduced for 24% and 42% versus plastic and elastic bracing, respectively. EBPA showed to be from 40% to 70% more effective than benchmarked individual treatments, with low NNT. The burden of treatment was frequently reduced, but it had to be increased even more frequently

Global Analysis of Aerosol Properties Above Clouds

The seasonal and spatial varability of Aerosol Above Cloud (AAC) properties are derived from passive satellite data for the year 2008. A significant amount of aerosols are transported above liquid water clouds on the global scale. For particles in the fine mode (i.e., radius smaller than 0.3 m), including both clear sky and AAC retrievals increases the global mean aerosol optical thickness by 25(+/- 6%). The two main regions with man-made AAC are the tropical Southeast Atlantic, for biomass burning aerosols, and the North Pacific, mainly for pollutants. Man-made AAC are also detected over the Arctic during the spring. Mineral dust particles are detected above clouds within the so-called dust belt region (5-40 N). AAC may cause a warming effect and bias the retrieval of the cloud properties. This study will then help to better quantify the impacts of aerosols on clouds and climate

Observation of absorbing aerosols above clouds over the south-east Atlantic Ocean from the geostationary satellite SEVIRI – Part 1: Method description and sensitivity

This is the final version. Available on open access from EGU via the DOI in this recordData availability: The data used for this study are available from the corresponding author, FP, upon reasonable request.High-temporal-resolution observations from satellites have a great potential for studying the impact of biomass burning aerosols and clouds over the south-east Atlantic Ocean (SEAO). This paper presents a method developed to simultaneously retrieve aerosol and cloud properties in aerosol above-cloud conditions from the geostationary instrument Meteosat Second Generation/Spinning Enhanced Visible and Infrared Imager (MSG/SEVIRI). The above-cloud aerosol optical thickness (AOT), the cloud optical thickness (COT) and the cloud droplet effective radius (CER) are derived from the spectral contrast and the magnitude of the signal measured in three channels in the visible to shortwave infrared region. The impact of the absorption from atmospheric gases on the satellite signal is corrected by applying transmittances calculated using the water vapour profiles from a Met Office forecast model. The sensitivity analysis shows that a 10 % error on the humidity profile leads to an 18.5 % bias on the above-cloud AOT, which highlights the importance of an accurate atmospheric correction scheme. In situ measurements from the CLARIFY-2017 airborne field campaign are used to constrain the aerosol size distribution and refractive index that is assumed for the aforementioned retrieval algorithm. The sensitivities in the retrieved AOT, COT and CER to the aerosol model assumptions are assessed. Between 09:00 and 15:00 UTC, an uncertainty of 40 % is estimated on the above-cloud AOT, which is dominated by the sensitivity of the retrieval to the single-scattering albedo. The absorption AOT is less sensitive to the aerosol assumptions with an uncertainty generally lower than 17 % between 09:00 and 15:00 UTC. Outside of that time range, as the scattering angle decreases, the sensitivity of the AOT and the absorption AOT to the aerosol model increases. The retrieved cloud properties are only weakly sensitive to the aerosol model assumptions throughout the day, with biases lower than 6 % on the COT and 3 % on the CER. The stability of the retrieval over time is analysed. For observations outside of the backscattering glory region, the time series of the aerosol and cloud properties are physically consistent, which confirms the ability of the retrieval to monitor the temporal evolution of aerosol above-cloud events over the SEAO.Research Council of NorwayNetB

Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration

Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on β-cell growth, differentiation and regeneration. Finally, we describe a peculiar vascular phenotype in tcf7l2 mutant larvae, characterized by significant reduction in the average number and diameter of pancreatic islet capillaries. Overall, the zebrafish Tcf7l2 mutant, characterized by hyperglycemia, pancreatic and vascular defects, and reduced regeneration proves to be a suitable model to study the mechanism of action and the pleiotropic effects of Tcf7l2, the most relevant T2D GWAS hit in human populations. © 2017 The Author(s)

Comparison of aerosol optical properties above clouds between POLDER and AeroCom models over the South East Atlantic Ocean during the fire season

Aerosol properties above clouds have been retrieved over the South East Atlantic Ocean during the fire season 2006 using satellite observations from POLDER (Polarization and Directionality of Earth Reflectances). From June to October, POLDER has observed a mean Above-Cloud Aerosol Optical Thickness (ACAOT) of 0.28 and a mean Above-Clouds Single Scattering Albedo (ACSSA) of 0.87 at 550 nm. These results have been used to evaluate the simulation of aerosols above clouds in 5 AeroCom (Aerosol Comparisons between Observations and Models) models (GOCART, HadGEM3, ECHAM5-HAM2, OsloCTM2 and SPRINTARS). Most models do not reproduce the observed large aerosol load episodes. The comparison highlights the importance of the injection height and the vertical transport parameterizations to simulate the large ACAOT observed by POLDER. Furthermore, POLDER ACSSA is best reproduced by models with a high imaginary part of black carbon refractive index, in accordance with recent recommendations

VennPlex--a novel Venn diagram program for comparing and visualizing datasets with differentially regulated datapoints.

With the development of increasingly large and complex genomic and proteomic data sets, an enhancement in the complexity of available Venn diagram analytical programs is becoming increasingly important. Current freely available Venn diagram programs often fail to represent extra complexity among datasets, such as regulation pattern differences between different groups. Here we describe the development of VennPlex, a program that illustrates the often diverse numerical interactions among multiple, high-complexity datasets, using up to four data sets. VennPlex includes versatile output features, where grouped data points in specific regions can be easily exported into a spreadsheet. This program is able to facilitate the analysis of two to four gene sets and their corresponding expression values in a user-friendly manner. To demonstrate its unique experimental utility we applied VennPlex to a complex paradigm, i.e. a comparison of the effect of multiple oxygen tension environments (1–20% ambient oxygen) upon gene transcription of primary rat astrocytes. VennPlex accurately dissects complex data sets reliably into easily identifiable groups for straightforward analysis and data output. This program, which is an improvement over currently available Venn diagram programs, is able to rapidly extract important datasets that represent the variety of expression patterns available within the data sets, showing potential applications in fields like genomics, proteomics, and bioinformatics

Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing

Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5'-TOP or TCT). By addressing the developmental regulation of TSS selection in zebrafish we uncovered a class of dual-initiation promoters in thousands of genes, including snoRNA host genes. 5'-TOP/TCT initiation is intertwined with canonical initiation and used divergently in hundreds of dual-initiation promoters during maternal to zygotic transition. Dual-initiation in snoRNA host genes selectively generates host and snoRNA with often different spatio-temporal expression. Dual-initiation promoters are pervasive in human and fruit fly, reflecting evolutionary conservation. We propose that dual-initiation on shared promoters represents a composite promoter architecture, which can function both coordinately and divergently to diversify RNAs

Researching digital inequalities in children’s play with technology in South Africa

This paper reports on the South African findings from an international mixed methods study between the LEGO Foundation, Dubit and the Universities of Sheffield (England) and Cape Town (South Africa) on young children’s learning with digital technology. The findings of the study, the first of its kind in South Africa, show the consistency of qualities and experience of play, but also reveal socio-economic, linguistic, ethnic, gender and racial inequalities in the play environments of both groups of 3–11-year-olds. Yet, despite these structural inequalities, the play ecologies of children in resource-constrained environments show their creativity within the digital/non-digital environment. The paper discusses some of the analytical tools used and the geo-political issues raised, and considers these in conjunction with selected data. We conclude that the different socio-cultural conditions and geo-political realities offer new insights about the role global education research can play in helping combat structural inequalities in resource-constrained environments

Regressive evolution of an effector following a host jump in the Irish potato famine pathogen lineage

In order to infect a new host species, the pathogen must evolve to enhance infection and transmission in the novel environment. Although we often think of evolution as a process of accumulation, it is also a process of loss. Here, we document an example of regressive evolution of an effector activity in the Irish potato famine pathogen (Phytophthora infestans) lineage, providing evidence that a key sequence motif in the effector PexRD54 has degenerated following a host jump. We began by looking at PexRD54 and PexRD54-like sequences from across Phytophthora species. We found that PexRD54 emerged in the common ancestor of Phytophthora clade 1b and 1c species, and further sequence analysis showed that a key functional motif, the C-terminal ATG8-interacting motif (AIM), was also acquired at this point in the lineage. A closer analysis showed that the P. mirabilis PexRD54 (PmPexRD54) AIM is atypical, the otherwise-conserved central residue mutated from a glutamate to a lysine. We aimed to determine whether this PmPexRD54 AIM polymorphism represented an adaptation to the Mirabilis jalapa host environment. We began by characterizing the M. jalapa ATG8 family, finding that they have a unique evolutionary history compared to previously characterized ATG8s. Then, using co-immunoprecipitation and isothermal titration calorimetry assays, we showed that both full-length PmPexRD54 and the PmPexRD54 AIM peptide bind weakly to the M. jalapa ATG8s. Through a combination of binding assays and structural modelling, we showed that the identity of the residue at the position of the PmPexRD54 AIM polymorphism can underpin high-affinity binding to plant ATG8s. Finally, we conclude that the functionality of the PexRD54 AIM was lost in the P. mirabilis lineage, perhaps owing to as-yet-unknown selection pressure on this effector in the new host environment