OMA orthology in 2024: improved prokaryote coverage, ancestral and extant GO enrichment, a revamped synteny viewer and more in the OMA Ecosystem.

In this update paper, we present the latest developments in the OMA browser knowledgebase, which aims to provide high-quality orthology inferences and facilitate the study of gene families, genomes and their evolution. First, we discuss the addition of new species in the database, particularly an expanded representation of prokaryotic species. The OMA browser now offers Ancestral Genome pages and an Ancestral Gene Order viewer, allowing users to explore the evolutionary history and gene content of ancestral genomes. We also introduce a revamped Local Synteny Viewer to compare genomic neighborhoods across both extant and ancestral genomes. Hierarchical Orthologous Groups (HOGs) are now annotated with Gene Ontology annotations, and users can easily perform extant or ancestral GO enrichments. Finally, we recap new tools in the OMA Ecosystem, including OMAmer for proteome mapping, OMArk for proteome quality assessment, OMAMO for model organism selection and Read2Tree for phylogenetic species tree construction from reads. These new features provide exciting opportunities for orthology analysis and comparative genomics. OMA is accessible at https://omabrowser.org.

Ultrasound-detected tibial artery calcification as a marker of cardiovascular and lower-limb risk in asymptomatic patients with type-2 diabetes.

BACKGROUND: Medial arterial calcification (MAC) is a vascular disease distinct from atherosclerosis. Recently, several studies have demonstrated that MAC is an important marker of cardiovascular events. We aim to assess the presence of MAC during ultrasound screening of lower-limb vasculature and its association with both cardiovascular (CV) and lower-limb events in patients with type-2 diabetes. METHODS: A retrospective cohort study was conducted on 1119 patients with type-2 diabetes free from CV disease. A CV work-up, including vascular ultrasound, was performed for each patient. The presence of MAC was assessed on posterior tibial arteries and ankle-brachial index (ABI) was measured. Major acute CV events (MACEs) and lower-limb events (MALEs) were recorded as a composite endpoint for a 5-year period. RESULTS: We identified MAC among 212 (18.9%) patients. The independent determinants of MAC were age and diabetic retinopathy. Over a period of 5 years, 125 MACEs and 22 MALEs occurred. MAC was significantly associated with the composite outcome MACE + MALE (HR = 1.94; 95% CI: 1.23, 3.08, p = 0.005) or with MACE (HR = 1.85; 95% CI: 1.16, 2.95, p = 0.010). Adjusted for ABI and diabetic foot wound, MAC remained a determinant of MALE (HR = 5.49; 95% CI: 2.19, 13.76, p < 0.001). Considering each ABI group, MAC was associated with both MACE and MALE in the normal ABI group. CONCLUSIONS: Ultrasound-detected MAC on tibial arteries seems to be a determinant of both CV and lower-limb events, independent from ABI. MAC helps to refine the CV risk in patients with normal ABI.

YB-1 unwinds mRNA secondary structures in vitro and negatively regulates stress granule assembly in HeLa cells.

In the absence of the scanning ribosomes that unwind mRNA coding sequences and 5'UTRs, mRNAs are likely to form secondary structures and intermolecular bridges. Intermolecular base pairing of non polysomal mRNAs is involved in stress granule (SG) assembly when the pool of mRNAs freed from ribosomes increases during cellular stress. Here, we unravel the structural mechanisms by which a major partner of dormant mRNAs, YB-1 (YBX1), unwinds mRNA secondary structures without ATP consumption by using its conserved cold-shock domain to destabilize RNA stem/loops and its unstructured C-terminal domain to secure RNA unwinding. At endogenous levels, YB-1 facilitates SG disassembly during arsenite stress recovery. In addition, overexpression of wild-type YB-1 and to a lesser extent unwinding-defective mutants inhibit SG assembly in HeLa cells. Through its mRNA-unwinding activity, YB-1 may thus inhibit SG assembly in cancer cells and package dormant mRNA in an unfolded state, thus preparing mRNAs for translation initiation.

OMA orthology in 2021: website overhaul, conserved isoforms, ancestral gene order and more.

OMA is an established resource to elucidate evolutionary relationships among genes from currently 2326 genomes covering all domains of life. OMA provides pairwise and groupwise orthologs, functional annotations, local and global gene order conservation (synteny) information, among many other functions. This update paper describes the reorganisation of the database into gene-, group- and genome-centric pages. Other new and improved features are detailed, such as reporting of the evolutionarily best conserved isoforms of alternatively spliced genes, the inferred local order of ancestral genes, phylogenetic profiling, better cross-references, fast genome mapping, semantic data sharing via RDF, as well as a special coronavirus OMA with 119 viruses from the Nidovirales order, including SARS-CoV-2, the agent of the COVID-19 pandemic. We conclude with improvements to the documentation of the resource through primers, tutorials and short videos. OMA is accessible at https://omabrowser.org.

Leveraging PEPFAR-Supported Health Information Systems for COVID-19 Pandemic Response.

Since 2003, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported implementation and maintenance of health information systems for HIV/AIDS and related diseases, such as tuberculosis, in numerous countries. As the COVID-19 pandemic emerged, several countries conducted rapid assessments and enhanced existing PEPFAR-funded HIV and national health information systems to support COVID-19 surveillance data collection, analysis, visualization, and reporting needs. We describe efforts at the US Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia, USA, and CDC country offices that enhanced existing health information systems in support COVID-19 pandemic response. We describe CDC activities in Haiti as an illustration of efforts in PEPFAR countries. We also describe how investments used to establish and maintain standards-based health information systems in resource-constrained settings can have positive effects on health systems beyond their original scope.

[Responding to children's emotional and cognitive needs: Applying the cumulative model to the general population]. / La réponse aux besoins affectifs et cognitifs de l'enfant : Application du modèle cumulatif à la population générale.

OBJECTIVES: Several risk factors are associated with neglectful behaviors. Yet their cumulative effect, which refers to the accumulation of risk regardless of the presence or absence of specific factors, remains unknown. This study aims to determine whether risk accumulation predicts caregivers' responses to children's emotional and cognitive needs in the general population and to examine the presence of clinical thresholds. METHOD: A total of 1102 maternal figures of children aged 5 to 9 years old living in Quebec were questioned through a telephone survey. The response to children's emotional and cognitive needs was measured using a validated version of the Parent-Report Multidimensional Neglectful Behavior Scale. Ten individual, family and socioeconomic risk factors were combined to compute a cumulative risk index. RESULTS: Results indicate that the cumulative index predicts the response to children's emotional and cognitive needs in the general population. This effect is observed for families exposed to at least two risk factors and it increases considerably when risk exposure reaches 5 factors. CONCLUSIONS: This study supports the cumulative risk hypothesis, which until now had mainly been examined in vulnerable or clinical samples. It fosters a better statistical understanding of contexts compromising an optimal response to school age children's emotional and cognitive needs in the general population. This breakthrough is particularity important considering the challenges of identifying children at risk of having their needs neglected.

OBJECTIFS: Plusieurs facteurs de risque sont associés à des conduites à caractère négligent. Leur effet cumulatif, soit l'accumulation du risque indépendamment de la présence ou de l'absence de facteurs spécifiques, est toutefois méconnu. La présente étude a pour objectif de déterminer si le cumul prédit la réponse aux besoins affectifs et cognitifs de l'enfant dans la population générale et d'examiner la présence d'un seuil critique. MÉTHODE: Un total de 1 102 figures maternelles ayant des enfants âgés de 5 à 9 ans vivant au Québec ont été questionnées par le biais d'un sondage téléphonique. La réponse aux besoins affectifs et cognitifs de l'enfant a été mesurée à l'aide d'une adaptation validée de l'échelle multidimensionnelle des conduites de négligence. Dix facteurs de risque individuels, familiaux et socioéconomiques ont été combinés afin de calculer un indice de risque cumulatif. RÉSULTATS: Les résultats montrent que l'indice cumulatif prédit la réponse aux besoins affectifs et cognitifs de l'enfant dans la population générale. Cet effet est observé pour les familles présentant au minimum deux facteurs de risque et augmente de manière importante lors d'une exposition à cinq facteurs. CONCLUSIONS: La présente étude appuie l'hypothèse du cumul, qui avait jusqu'à présent, principalement été examinée au sein d'échantillons vulnérables ou cliniques. Elle favorise une meilleure compréhension statistique des contextes qui rendent difficiles la réponse de l'environnement de l'enfant d'âge scolaire à ses besoins affectifs et cognitifs dans la population générale. Cette avancée est d'autant plus importante considérant les défis liés à l'identification des enfants à risque de voir leurs besoins négligés.

Transcompp: understanding phenotypic plasticity by estimating Markov transition rates for cell state transitions.

MOTIVATION: Gradual population-level changes in tissues can be driven by stochastic plasticity, meaning rare stochastic transitions of single-cell phenotype. Quantifying the rates of these stochastic transitions requires time-intensive experiments, and analysis is generally confounded by simultaneous bidirectional transitions and asymmetric proliferation kinetics. To quantify cellular plasticity, we developed Transcompp (Transition Rate ANalysis of Single Cells to Observe and Measure Phenotypic Plasticity), a Markov modeling algorithm that uses optimization and resampling to compute best-fit rates and statistical intervals for stochastic cell-state transitions. RESULTS: We applied Transcompp to time-series datasets in which purified subpopulations of stem-like or non-stem cancer cells were exposed to various cell culture environments, and allowed to re-equilibrate spontaneously over time. Results revealed that commonly used cell culture reagents hydrocortisone and cholera toxin shifted the cell population equilibrium toward stem-like or non-stem states, respectively, in the basal-like breast cancer cell line MCF10CA1a. In addition, applying Transcompp to patient-derived cells showed that transition rates computed from short-term experiments could predict long-term trajectories and equilibrium convergence of the cultured cell population. AVAILABILITY AND IMPLEMENTATION: Freely available for download at http://github.com/nsuhasj/Transcompp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Thermal adaptation rather than demographic history drives genetic structure inferred by copy number variants in a marine fish.

Increasing evidence shows that structural variants represent an overlooked aspect of genetic variation with consequential evolutionary roles. Among those, copy number variants (CNVs), including duplicated genomic regions and transposable elements (TEs), may contribute to local adaptation and/or reproductive isolation among divergent populations. Those mechanisms suppose that CNVs could be used to infer neutral and/or adaptive population genetic structure, whose study has been restricted to microsatellites, mitochondrial DNA and Amplified fragment length polymorphism markers in the past and more recently the use of single nucleotide polymorphisms (SNPs). Taking advantage of recent developments allowing CNV analysis from RAD-seq data, we investigated how variation in fitness-related traits, local environmental conditions and demographic history are associated with CNVs, and how subsequent copy number variation drives population genetic structure in a marine fish, the capelin (Mallotus villosus). We collected 1538 DNA samples from 35 sampling sites in the north Atlantic Ocean and identified 6620 putative CNVs. We found associations between CNVs and the gonadosomatic index, suggesting that six duplicated regions could affect female fitness by modulating oocyte production. We also detected 105 CNV candidates associated with water temperature, among which 20% corresponded to genomic regions located within the sequence of protein-coding genes, suggesting local adaptation to cold water by means of gene sequence amplification. We also identified 175 CNVs associated with the divergence of three previously defined parapatric glacial lineages, of which 24% were located within protein-coding genes, making those loci potential candidates for reproductive isolation. Lastly, our analyses unveiled a hierarchical, complex CNV population structure determined by temperature and local geography, which was in stark contrast to that inferred based on SNPs in a previous study. Our findings underline the complementarity of those two types of genomic variation in population genomics studies.

Estimation of the Width of Uncertainty in Care Consumption and Costs When Using Common Data Collection Tools in Economic Evaluations: A Benchmark for Sensitivity Analyses.

OBJECTIVES: This study aimed to evaluate the uncertainty related to the use of common collection tools to assess costs in economic evaluations compared with an exhaustive administrative database. METHODS: A pragmatic study was performed using preexisting cost-effectiveness studies. Patients were probabilistically matched with themselves in the French National Health Data System (Système National des Données de Santé [SNDS]), and all their reimbursed hospital and ambulatory care data during the study were extracted. Outcomes included the ratio of the number of each type of resources consumed using trial data (case report forms for ambulatory care and local hospital data for hospital care) versus the SNDS and the ratio of corresponding costs. Mean ratios and 95% confidence intervals (CIs) were calculated using bootstrapping. The impact of the collection tool on the result of the economic evaluation was calculated with the difference in costs between the 2 treatment arms with both collection methods. RESULTS: Five cost-effectiveness studies were included in the analysis. A total of 397 patients had the SNDS hospital data, and 321 had ambulatory care data. Common collection tools underestimated hospital admissions by 13% (95% CI 8-20), corresponding costs by 5% (95% CI 2-14), and ambulatory acts by 41% (95% CI 33-51), with large variations in costs depending on the study. There was no change in the economic conclusion in any study. CONCLUSIONS: The use of common collection tools underestimates healthcare resource consumption and its associated costs, particularly for ambulatory care. Our results could provide useful evidence-based estimates to inform sensitivity analyses' parameters in future cost-effectiveness analyses.

YB-1, an abundant core mRNA-binding protein, has the capacity to form an RNA nucleoprotein filament: a structural analysis.

The structural rearrangements accompanying mRNA during translation in mammalian cells remain poorly understood. Here, we discovered that YB-1 (YBX1), a major partner of mRNAs in the cytoplasm, forms a linear nucleoprotein filament with mRNA, when part of the YB-1 unstructured C-terminus has been truncated. YB-1 possesses a cold-shock domain (CSD), a remnant of bacterial cold shock proteins that have the ability to stimulate translation under the low temperatures through an RNA chaperone activity. The structure of the nucleoprotein filament indicates that the CSD of YB-1 preserved its chaperone activity also in eukaryotes and shows that mRNA is channeled between consecutive CSDs. The energy benefit needed for the formation of stable nucleoprotein filament relies on an electrostatic zipper mediated by positively charged amino acid residues in the YB-1 C-terminus. Thus, YB-1 displays a structural plasticity to unfold structured mRNAs into extended linear filaments. We anticipate that our findings will shed the light on the scanning of mRNAs by ribosomes during the initiation and elongation steps of mRNA translation.

Making sense of the French public hospital system: a network-based approach to hospital clustering using unsupervised learning methods.

BACKGROUND: Hospitals in the public and private sectors tend to join larger organizations to form hospital groups. This increasingly frequent mode of functioning raises the question of how countries should organize their health system, according to the interactions already present between their hospitals. The objective of this study was to identify distinctive profiles of French hospitals according to their characteristics and their role in the French hospital network. METHODS: Data were extracted from the national hospital database for year 2016. The database was restricted to public hospitals that practiced medicine, surgery or obstetrics. Hospitals profiles were determined using the k-means method. The variables entered in the clustering algorithm were: the number of stays, the effective diversity of hospital activity, and a network-based mobility indicator (proportion of stays followed by another stay in a different hospital of the same Regional Hospital Group within 90 days). RESULTS: Three hospital groups were identified by the clustering algorithm. The first group was constituted of 34 large hospitals (median 82,100 annual stays, interquartile range 69,004 - 117,774) with a very diverse activity. The second group contained medium-sized hospitals (with a median of 258 beds, interquartile range 164 - 377). The third group featured less diversity regarding the type of stay (with a mean of 8 effective activity domains, standard deviation 2.73), a smaller size and a higher proportion of patients that subsequently visited other hospitals (11%). The most frequent type of patient mobility occurred from the hospitals in group 2 to the hospitals in group 1 (29%). The reverse direction was less frequent (19%). CONCLUSIONS: The French hospital network is organized around three categories of public hospitals, with an unbalanced and disassortative patient flow. This type of organization has implications for hospital planning and infectious diseases control.

Organismal Aging and Oxidants beyond Macromolecules Damage.

The relationship between oxidants and organismal aging was first articulated through the free radical theory of aging. One of the major predictions of the free radical theory of aging is that oxidative stress shortens organisms' lifespan because of an increased level of oxidants, which are damaging to macromolecules. However, challenging the role of oxidants in age-related diseases, there is now sufficient evidence that antioxidant supplements do not provide significant health benefits. Interestingly, in addition to an increase in oxidant-mediated macromolecules damage, there is convincing experimental data to support the role of senescent cells in the process of aging. Here, the current knowledge regarding the role of oxidants and cellular senescence in organismal aging is reviewed and it is proposed that, in addition to the role of oxidants as inducers of macromolecular damage, oxidants may also function as regulators of signaling pathways involved in the establishment of cellular senescence. If this role for oxidants is established, it may be necessary to modify the free radical theory of aging from "Organisms age because cells accumulate reactive oxygen species-dependent damage over time" to: "Organisms age because cells accumulate oxidants'-dependent damage and oxidants'-dependent senescent characteristics over time."

Phylogenetic approaches to identifying fragments of the same gene, with application to the wheat genome.

MOTIVATION: As the time and cost of sequencing decrease, the number of available genomes and transcriptomes rapidly increases. Yet the quality of the assemblies and the gene annotations varies considerably and often remains poor, affecting downstream analyses. This is particularly true when fragments of the same gene are annotated as distinct genes, which may cause them to be mistaken as paralogs. RESULTS: In this study, we introduce two novel phylogenetic tests to infer non-overlapping or partially overlapping genes that are in fact parts of the same gene. One approach collapses branches with low bootstrap support and the other computes a likelihood ratio test. We extensively validated these methods by (i) introducing and recovering fragmentation on the bread wheat, Triticum aestivum cv. Chinese Spring, chromosome 3B; (ii) by applying the methods to the low-quality 3B assembly and validating predictions against the high-quality 3B assembly; and (iii) by comparing the performance of the proposed methods to the performance of existing methods, namely Ensembl Compara and ESPRIT. Application of this combination to a draft shotgun assembly of the entire bread wheat genome revealed 1221 pairs of genes that are highly likely to be fragments of the same gene. Our approach demonstrates the power of fine-grained evolutionary inferences across multiple species to improving genome assemblies and annotations. AVAILABILITY AND IMPLEMENTATION: An open source software tool is available at https://github.com/DessimozLab/esprit2. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

iHam and pyHam: visualizing and processing hierarchical orthologous groups.

SUMMARY: The evolutionary history of gene families can be complex due to duplications and losses. This complexity is compounded by the large number of genomes simultaneously considered in contemporary comparative genomic analyses. As provided by several orthology databases, hierarchical orthologous groups (HOGs) are sets of genes that are inferred to have descended from a common ancestral gene within a species clade. This implies that the set of HOGs defined for a particular clade correspond to the ancestral genes found in its last common ancestor. Furthermore, by keeping track of HOG composition along the species tree, it is possible to infer the emergence, duplications and losses of genes within a gene family of interest. However, the lack of tools to manipulate and analyse HOGs has made it difficult to extract, display and interpret this type of information. To address this, we introduce interactive HOG analysis method, an interactive JavaScript widget to visualize and explore gene family history encoded in HOGs and python HOG analysis method, a python library for programmatic processing of genes families. These complementary open source tools greatly ease adoption of HOGs as a scalable and interpretable concept to relate genes across multiple species. AVAILABILITY AND IMPLEMENTATION: iHam's code is available at https://github.com/DessimozLab/iHam or can be loaded dynamically. pyHam's code is available at https://github.com/DessimozLab/pyHam and or via the pip package 'pyham'.

Divergent and linked selection shape patterns of genomic differentiation between European and North American Atlantic salmon (Salmo salar).

As populations diverge many processes can shape genomic patterns of differentiation. Regions of high differentiation can arise due to divergent selection acting on selected loci, genetic hitchhiking of nearby loci, or through repeated selection against deleterious alleles (linked background selection); this divergence may then be further elevated in regions of reduced recombination. Atlantic salmon (Salmo salar) from Europe and North America diverged >600,000 years ago and despite some evidence of secondary contact, the majority of genetic data indicate substantial divergence between lineages. This deep divergence with potential gene flow provides an opportunity to investigate the role of different mechanisms that shape the genomic landscape during early speciation. Here, using 184,295 single nucleotide polymorphisms (SNPs) and 80 populations, we investigate the genomic landscape of differentiation across the Atlantic Ocean with a focus on highly differentiated regions and the processes shaping them. We found evidence of high (mean FST  = 0.26) and heterogeneous genomic differentiation between continents. Genomic regions associated with high trans-Atlantic differentiation ranged in size from single loci (SNPs) within important genes to large regions (1-3 Mbp) on four chromosomes (Ssa06, Ssa13, Ssa16 and Ssa19). These regions showed signatures consistent with selection, including high linkage disequilibrium, despite no significant reduction in recombination. Genes and functional enrichment of processes associated with differentiated regions may highlight continental differences in ocean navigation and parasite resistance. Our results provide insight into potential mechanisms underlying differences between continents, and evidence of near-fixed and potentially adaptive trans-Atlantic differences concurrent with a background of high genome-wide differentiation supports subspecies designation in Atlantic salmon.

Shared ancestral polymorphisms and chromosomal rearrangements as potential drivers of local adaptation in a marine fish.

Gene flow has tremendous importance for local adaptation, by influencing the fate of de novo mutations, maintaining standing genetic variation and driving adaptive introgression. Furthermore, structural variation as chromosomal rearrangements may facilitate adaptation despite high gene flow. However, our understanding of the evolutionary mechanisms impending or favouring local adaptation in the presence of gene flow is still limited to a restricted number of study systems. In this study, we examined how demographic history, shared ancestral polymorphism, and gene flow among glacial lineages contribute to local adaptation to sea conditions in a marine fish, the capelin (Mallotus villosus). We first assembled a 490-Mbp draft genome of M. villosus to map our RAD sequence reads. Then, we used a large data set of genome-wide single nucleotide polymorphisms (25,904 filtered SNPs) genotyped in 1,310 individuals collected from 31 spawning sites in the northwest Atlantic. We reconstructed the history of divergence among three glacial lineages and showed that they probably diverged from 3.8 to 1.8 million years ago and experienced secondary contacts. Within each lineage, our analyses provided evidence for large Ne and high gene flow among spawning sites. Within the Northwest Atlantic lineage, we detected a polymorphic chromosomal rearrangement leading to the occurrence of three haplogroups. Genotype-environment associations revealed molecular signatures of local adaptation to environmental conditions prevailing at spawning sites. Our study also suggests that both shared polymorphisms among lineages, resulting from standing genetic variation or introgression, and chromosomal rearrangements may contribute to local adaptation in the presence of high gene flow.

The OMA orthology database in 2018: retrieving evolutionary relationships among all domains of life through richer web and programmatic interfaces.

The Orthologous Matrix (OMA) is a leading resource to relate genes across many species from all of life. In this update paper, we review the recent algorithmic improvements in the OMA pipeline, describe increases in species coverage (particularly in plants and early-branching eukaryotes) and introduce several new features in the OMA web browser. Notable improvements include: (i) a scalable, interactive viewer for hierarchical orthologous groups; (ii) protein domain annotations and domain-based links between orthologous groups; (iii) functionality to retrieve phylogenetic marker genes for a subset of species of interest; (iv) a new synteny dot plot viewer; and (v) an overhaul of the programmatic access (REST API and semantic web), which will facilitate incorporation of OMA analyses in computational pipelines and integration with other bioinformatic resources. OMA can be freely accessed at https://omabrowser.org.

Developmental and sequenced one-to-one educational intervention (DS1-EI) for autism spectrum disorder and intellectual disability: a two-year interim report of a randomized single-blind multicenter controlled trial.

BACKGROUND: Children with autism spectrum disorder (ASD) and moderate to severe intellectual disability (ID) face many challenges. There is little evidence-based research into educational settings for children with ID and ASD and in France. Little is known about how this unserved population could benefit from intervention and education. This study assessed the feasibility and efficacy of a new intervention model using an individualized educational approach. METHODS: We conducted a randomized, single-blind controlled trial to assess a novel intervention: the "Developmental and Sequenced One-to-One Intervention (DS1-EI)". In DS1-EI, trained teachers worked one-to-one with each child in a small classroom setting, offering 10 h per week of the intervention. The focus was on encouraging spontaneous communication, promoting skills through play with peers, supporting positive interactions, and developmental and sequenced learning. We enrolled 5- to 9-year-old children with ASD and ID across 11 French child care institutions for children with co-occurring ASD and ID. Participants were matched in dyads by developmental quotient and randomized to the treatment-as-usual (TAU) group or the DS1-EI group. Independent raters blindly assessed the primary variables: The Childhood Autism Rating scale (CARS) and the Psychoeducational Profile, third edition (PEP-3). The secondary variables included the Vineland Adaptive Behavior Scale II (VABS-II) and the Clinical Global Assessment Scale (CGAS). Here we perform interim analyses at 24 months. RESULTS: At baseline, 72 participants were randomized. Nine patients (5 in the DS1-EI group and 4 in the TAU group) dropped out of the study. Using linear mixed models, both intent-to-treat (ITT) and per-protocol (PP) analyses at the 12-, 18- and 24-month outcomes showed no significant group nor group-by-time interaction effects. However, we found significant improvements in most primary and secondary variables over time in both groups. CONCLUSIONS: The study did not show that DS1-EI was superior to TAU in treating children with ASD and ID over 24 months. However, the low dropout rate shows that DS1-EI is feasible, and well accepted. As the study is still ongoing, we need to wait for data at 36 months to ensure whether DS1-EI could be recommended. TRIAL REGISTRATION: ANSM130282B-31 (April 16, 2013) and ACTRN12616000592448. Registered 6 May 2016, retrospectively registered, http://www.anzctr.org.au/.

Community Readiness for Child Maltreatment Prevention: The Challenge of a Brief Assessment.

In this paper, we address the assessment of community readiness (CR) for the prevention of child maltreatment in the context of a community survey. A mail survey was administered to 222 service providers and 54 supervisors and managers from 35 different organizations serving children and their families in four Canadian communities. Eleven items from the short version of the Readiness Assessment for the Prevention of Child Maltreatment (RAP-CM) were used, in combination with questions assessing knowledge of family support programs offered in the community and a measure of inter-agency collaboration. Findings show that a consistent and valid indicator of "Lack of knowledge of the environment" can be derived from the RAP-CM items and used for screening key informants. Overall, CR appears mixed in the communities studied, the weakest dimensions of which are the will to address the problem and the dynamism of informal social resources. Leadership emerges as a major gap that needs to be addressed.

Standardized benchmarking in the quest for orthologs.

Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision-recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods.