Prediction of multiple infections after severe burn trauma: a prospective cohort study.

OBJECTIVE: To develop predictive models for early triage of burn patients based on hypersusceptibility to repeated infections. BACKGROUND: Infection remains a major cause of mortality and morbidity after severe trauma, demanding new strategies to combat infections. Models for infection prediction are lacking. METHODS: Secondary analysis of 459 burn patients (≥16 years old) with 20% or more total body surface area burns recruited from 6 US burn centers. We compared blood transcriptomes with a 180-hour cutoff on the injury-to-transcriptome interval of 47 patients (≤1 infection episode) to those of 66 hypersusceptible patients [multiple (≥2) infection episodes (MIE)]. We used LASSO regression to select biomarkers and multivariate logistic regression to built models, accuracy of which were assessed by area under receiver operating characteristic curve (AUROC) and cross-validation. RESULTS: Three predictive models were developed using covariates of (1) clinical characteristics; (2) expression profiles of 14 genomic probes; (3) combining (1) and (2). The genomic and clinical models were highly predictive of MIE status [AUROCGenomic = 0.946 (95% CI: 0.906-0.986); AUROCClinical = 0.864 (CI: 0.794-0.933); AUROCGenomic/AUROCClinical P = 0.044]. Combined model has an increased AUROCCombined of 0.967 (CI: 0.940-0.993) compared with the individual models (AUROCCombined/AUROCClinical P = 0.0069). Hypersusceptible patients show early alterations in immune-related signaling pathways, epigenetic modulation, and chromatin remodeling. CONCLUSIONS: Early triage of burn patients more susceptible to infections can be made using clinical characteristics and/or genomic signatures. Genomic signature suggests new insights into the pathophysiology of hypersusceptibility to infection may lead to novel potential therapeutic or prophylactic targets.

Female stick insects mate multiply to find compatible mates

Why females of many species mate multiply in the absence of direct benefits remains an open question in evolutionary ecology. Interacting and mating with multiple males can be costly to females in terms of time, resources, predation risk, and disease transmission. A number of indirect genetic benefits have been proposed to explain such behaviors, but the relative importance of these mechanisms in natural systems remains unclear. We tested for several direct and indirect benefits of polyandry in the walking stick Timema cristinae. We found no evidence of direct benefits with respect to longevity or fecundity. However, male x female genotypic interactions affected egg-hatching success and offspring production independent of relatedness, suggesting that mating with certain males benefits females and that the best male may differ for each female. Furthermore, multiply mated females biased paternity toward one or few males, and the extent of this bias was positively correlated to egg-hatching success. Our data, therefore, provide evidence for indirect benefits through compatibility effects in this species. By mating multiply, females may improve their chances of mating with a compatible male if compatibility cannot be assessed before mating. Such compatibility effects can explain the evolution and maintenance of polyandry in Timema and many other species.

CBS: an open platform that integrates predictive methods and epigenetics information to characterize conserved regulatory features in multiple Drosophila genomes.

Background: Information about the composition of regulatory regions is of great value for designing experiments to functionally characterize gene expression. The multiplicity of available applications to predict transcription factor binding sites in a particular locus contrasts with the substantial computational expertise that is demanded to manipulate them, which may constitute a potential barrier for the experimental community. Results: CBS (Conserved regulatory Binding Sites, http://compfly.bio.ub.es/CBS) is a public platform of evolutionarily conserved binding sites and enhancers predicted in multiple Drosophila genomes that is furnished with published chromatin signatures associated to transcriptionally active regions and other experimental sources of information. The rapid access to this novel body of knowledge through a user-friendly web interface enables non-expert users to identify the binding sequences available for any particular gene, transcription factor, or genome region. Conclusions: The CBS platform is a powerful resource that provides tools for data mining individual sequences and groups of co-expressed genes with epigenomics information to conduct regulatory screenings in Drosophila.

Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations.

OBJECTIVES: The objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance. METHODS: Nine clinical isolates (P-1 to P-9) were susceptibility tested by EUCAST EDef 7.2 and Etest. P-4, P-5, P-7, P-8 and P-9 were available for further studies. Relatedness was evaluated by MLST. Additional genes were analysed by sequencing (including FKS1, ERG11, ERG2 and TAC1) and gene expression by quantitative PCR (CDR1, CDR2 and ERG11). UV-spectrophotometry and GC-MS were used for sterol analyses. In vivo virulence was determined in the insect model Galleria mellonella and evaluated by log-rank Mantel-Cox tests. RESULTS: P-1 + P-2 were susceptible, P-3 + P-4 fluconazole resistant, P-5 pan-azole resistant, P-6 + P-7 pan-azole and echinocandin resistant and P-8 + P-9 MDR. MLST supported genetic relatedness among clinical isolates. P-4 harboured four changes in Erg11 (E266D, G307S, G450E and V488I), increased expression of ERG11 and CDR2 and a change in Tac1 (R688Q). P-5, P-7, P-8 and P-9 had an additional change in Erg11 (A61E), increased expression of CDR1, CDR2 and ERG11 (except for P-7) and a different amino acid change in Tac1 (R673L). Echinocandin-resistant isolates harboured the Fks1 S645P alteration. Polyene-resistant P-8 + P-9 lacked ergosterol and harboured a frameshift mutation in ERG2 (F105SfsX23). Virulence was attenuated (but equivalent) in the clinical isolates, but higher than in the azole- and echinocandin-resistant unrelated control strain. CONCLUSIONS: C. albicans demonstrates a diverse capacity to adapt to antifungal exposure. Potentially novel resistance-inducing mutations in TAC1, ERG11 and ERG2 require independent validation.

Modeling and manufacturability assessment of bistable quantum-dot cells

We have investigated the behavior of bistable cells made up of four quantum dots and occupied by two electrons, in the presence of realistic confinement potentials produced by depletion gates on top of a GaAs/AlGaAs heterostructure. Such a cell represents the basic building block for logic architectures based on the concept of quantum cellular automata (QCA) and of ground state computation, which have been proposed as an alternative to traditional transistor-based logic circuits. We have focused on the robustness of the operation of such cells with respect to asymmetries derived from fabrication tolerances. We have developed a two-dimensional model for the calculation of the electron density in a driven cell in response to the polarization state of a driver cell. Our method is based on the one-shot configuration-interaction technique, adapted from molecular chemistry. From the results of our simulations, we conclude that an implementation of QCA logic based on simple ¿hole arrays¿ is not feasible, because of the extreme sensitivity to fabrication tolerances. As an alternative, we propose cells defined by multiple gates, where geometrical asymmetries can be compensated for by adjusting the bias voltages. Even though not immediately applicable to the implementation of logic gates and not suitable for large scale integration, the proposed cell layout should allow an experimental demonstration of a chain of QCA cells.

What are the success factors for Spanish textile firms? An exploratory multiple-case study

The objective of this article is to identify differential traits of successful SMEs in comparison to average SME firms in the textile and clothing sector. The method used is the multiple case-study of 12 firms based on qualitative and quantitative data obtained by means of in-depth interviews. Building on recent academic literature, we use four main dimensions that may explain success: i) knowledge generation (R&D) and acquisition; ii) innovation activity; iii) product and market characteristics and iv) strategic characteristics. Our results indicate that a higher R&D intensity and knowledge acquisition do not explain success. The main differential characteristic is that successful firms have a higher level of innovation activity, since innovation is their strategic priority, being a result of perceiving the key success factors of their markets differently. From the analysis it also follows that the prevalent strategy of successful firms is the niche strategy, with a demand pull focus, and a high proximity to the customer

Fatal Outcome of Multiple Clinical Presentations of Human Herpesvirus 8-related Disease After Solid Organ Transplantation.

Kaposi sarcoma is the most common human herpesvirus 8 (HHV-8)-related disease described after solid organ transplantation. Multicentric Castleman disease and hemophagocytic syndrome are other potential HHV-8-induced entities but are less frequently reported. We describe the case of a liver transplant recipient who presented with an acute febrile illness 1 year after transplantation with a rapidly fatal outcome. Autopsy revealed 3 distinct HHV-8-related entities: Kaposi sarcoma, HHV-8-associated multicentric Castleman disease with microlymphomas and a severe hemophagocytic syndrome. Retrospective serologic tests suggested that HHV-8 was likely transmitted by the seropositive donor at the time of transplantation. To our knowledge, this is the first case of copresentation of 3 clinical presentations of HHV-8-mediated human disease in the post-transplant setting. Considering the absence of systematic screening of organ donors/recipients for HHV-8 infection, HHV-8-related illness should be suspected in transplant recipients who present with acute febrile illness, systemic symptoms, lymphadenopathies, and/or multiorgan failure to rapidly document the diagnosis and provide timely an adequate treatment.

Migration and horizontal gene transfer divide microbial genomes into multiple niches.

Horizontal gene transfer is central to microbial evolution, because it enables genetic regions to spread horizontally through diverse communities. However, how gene transfer exerts such a strong effect is not understood. Here we develop an eco-evolutionary model and show how genetic transfer, even when rare, can transform the evolution and ecology of microbes. We recapitulate existing models, which suggest that asexual reproduction will overpower horizontal transfer and greatly limit its effects. We then show that allowing immigration completely changes these predictions. With migration, the rates and impacts of horizontal transfer are greatly increased, and transfer is most frequent for loci under positive natural selection. Our analysis explains how ecologically important loci can sweep through competing strains and species. In this way, microbial genomes can evolve to become ecologically diverse where different genomic regions encode for partially overlapping, but distinct, ecologies. Under these conditions ecological species do not exist, because genes, not species, inhabit niches.

Is response to fire influenced by dietary specialization and mobility? A comparative study with multiple animal assemblages

Fire is a major agent involved in landscape transformation and an indirect cause of changes in species composition. Responses to fire may vary greatly depending on life histories and functional traits of species. We have examined the taxonomic and functional responses to fire of eight taxonomic animal groups displaying a gradient of dietary and mobility patterns: Gastropoda, Heteroptera, Formicidae, Coleoptera, Araneae, Orthoptera, Reptilia and Aves. The fieldwork was conducted in a Mediterranean protected area on 3 sites (one unburnt and two burnt with different postfire management practices) with five replicates per site. We collected information from 4606 specimens from 274 animal species. Similarity in species composition and abundance between areas was measured by the Bray-Curtis index and ANOSIM, and comparisons between animal and plant responses by Mantel tests. We analyze whether groups with the highest percentage of omnivorous species, these species being more generalist in their dietary habits, show weak responses to fire (i.e. more similarity between burnt and unburnt areas), and independent responses to changes in vegetation. We also explore how mobility, i.e. dispersal ability, influences responses to fire. Our results demonstrate that differences in species composition and abundance between burnt and unburnt areas differed among groups. We found a tendency towards presenting lower differences between areas for groups with higher percentages of omnivorous species. Moreover, taxa with a higher percentage of omnivorous species had significantly more independent responses of changes in vegetation. High- (e.g. Aves) and low-mobility (e.g. Gastropoda) groups had the strongest responses to fire (higher R scores of the ANOSIM); however, we failed to find a significant general pattern with all the groups according to their mobility. Our results partially support the idea that functional traits underlie the response of organisms to environmental changes caused by fire.