Redefining the bacteriophage mv4 site-specific recombination system and the sequence specificity of its attB and core-attP sites.

Through their involvement in the integration and excision of a large number of mobile genetic elements, such as phages and integrative and conjugative elements (ICEs), site-specific recombination systems based on heterobivalent tyrosine recombinases play a major role in genome dynamics and evolution. However, despite hundreds of these systems having been identified in genome databases, very few have been described in detail, with none from phages that infect Bacillota (formerly Firmicutes). In this study, we reanalyzed the recombination module of Lactobacillus delbrueckii subsp. bulgaricus phage mv4, previously considered atypical compared with classical systems. Our results reveal that mv4 integrase is a 369 aa protein with all the structural hallmarks of recombinases from the Tn916 family and that it cooperatively interacts with its recombination sites. Using randomized DNA libraries, NGS sequencing, and other molecular approaches, we show that the 21-bp core-attP and attB sites have structural similarities to classical systems only if considering the nucleotide degeneracy, with two 7-bp inverted regions corresponding to mv4Int core-binding sites surrounding a 7-bp strand-exchange region. We also examined the different compositional constraints in the core-binding regions, which define the sequence space of permissible recombination sites.

Apparent simplicity and emergent robustness in the control of the Escherichia coli cell cycle.

To examine how bacteria achieve robust cell proliferation across diverse conditions, we developed a method that quantifies 77 cell morphological, cell cycle, and growth phenotypes of a fluorescently labeled Escherichia coli strain and >800 gene deletion derivatives under multiple nutrient conditions. This approach revealed extensive phenotypic plasticity and deviating mutant phenotypes were often nutrient dependent. From this broad phenotypic landscape emerged simple and robust unifying rules (laws) that connect DNA replication initiation, nucleoid segregation, FtsZ ring formation, and cell constriction to specific aspects of cell size (volume, length, or added length) at the population level. Furthermore, completion of cell division followed the initiation of cell constriction after a constant time delay across strains and nutrient conditions, identifying cell constriction as a key control point for cell size determination. Our work provides a population-level description of the governing principles by which E. coli integrates cell cycle processes and growth rate with cell size to achieve its robust proliferative capability. A record of this paper's transparent peer review process is included in the supplemental information.

Spatial-temporal simulation for hospital infection spread and outbreaks of Clostridioides difficile.

Validated and curated datasets are essential for studying the spread and control of infectious diseases in hospital settings, requiring clinical information on patients' evolution and their location. The literature shows that approaches based on Artificial Intelligence (AI) in the development of clinical-support systems have benefits that are increasingly recognized. However, there is a lack of available high-volume data, necessary for trusting such AI models. One effective method in this situation involves the simulation of realistic data. Existing simulators primarily focus on implementing compartmental epidemiological models and contact networks to validate epidemiological hypotheses. Nevertheless, other practical aspects such as the hospital building distribution, shifts or safety policies on infections has received minimal attention. In this paper, we propose a novel approach for a simulator of nosocomial infection spread, combining agent-based patient description, spatial-temporal constraints of the hospital settings, and microorganism behavior driven by epidemiological models. The predictive validity of the model was analyzed considering micro and macro-face validation, parameter calibration based on literature review, model alignment, and sensitive analysis with an expert. This simulation model is useful in monitoring infections and in the decision-making process in a hospital, by helping to detect spatial-temporal patterns and predict statistical data about the disease.

Microbially induced calcium carbonate precipitation in fossil consolidation treatments: Preliminary results inducing exogenous Myxococcus xanthus bacteria in a miocene Cheirogaster richardi specimen.

This research paper proposes Microbially Induced Calcium Carbonate Precipitation (MICP) as an innovative approach for palaeontological heritage conservation, specifically on deteriorated carbonate fossils. Due to its efficiency in bioconsolidation of carbonate ornamental rocks, Myxococcus xanthus inoculation on carbonate fossils was studied in this research. Treatment was tested on nine fossil samples from decontextualized fragments of Cheirogaster richardi specimens (Can Mata site, Hostalets de Pierola, Catalonia, Spain). The main objective was to evaluate whether treatment with Myxococcus xanthus improved fossil surface cohesion and hardness and mechanical strength without significant physicochemical and aesthetic changes to the surface. Chemical compatibility of the treatment, penetration capacity and absence of noticeable changes in substrate porosity were considered as important issues to be evaluated. Samples were analysed, before and after treatment, by scanning electron microscopy, weight control, spectrophotometry, X-ray diffraction analysis, water absorption analysis, pH and conductivity control, Vickers microindentation and tape test. Results show that hardness increases by a factor of almost two. Cohesion also increases and surface disaggregated particles are bonded together by a calcium carbonate micrometric layer with no noticeable changes in surface roughness. Colour and gloss variations are negligible, and pH, conductivity and weight hardly change. Slight changes in porosity were observed but without total pore clogging. To sum up, results indicate that Myxococcus xanthus biomineralisation is an effective consolidation treatment for carbonate fossils and highly compatible with carbonate substrates. Furthermore, bacterial precipitation of calcium carbonate is a safe and eco-friendly consolidation treatment.

Atypical low-copy number plasmid segregation systems, all in one?

Plasmid families harbor different maintenances functions, depending on their size and copy number. Low copy number plasmids rely on active partition systems, organizing a partition complex at specific centromere sites that is actively positioned using NTPase proteins. Some low copy number plasmids lack an active partition system, but carry atypical intracellular positioning systems using a single protein that binds to the centromere site but without an associated NTPase. These systems have been studied in the case of the Escherichia coli R388 and of the Staphylococcus aureus pSK1 plasmids. Here we review these two systems, which appear to be unrelated but share common features, such as their distribution on plasmids of medium size and copy number, certain activities of their centromere-binding proteins, StbA and Par, respectively, as well as their mode of action, which may involve dynamic interactions with the nucleoid-packed chromosome of their hosts.

The use of networks in spatial and temporal computational models for outbreak spread in epidemiology: A systematic review.

OBJECTIVES: To examine recent literature in order to present a comprehensive overview of the current trends as regards the computational models used to represent the propagation of an infectious outbreak in a population, paying particular attention to those that represent network-based transmission. METHODS: a systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Papers published in English between 2010 and September 2021 were sought in the ACM Digital Library, IEEE Xplore, PubMed and Scopus databases. RESULTS: Upon considering their titles and abstracts, 832 papers were obtained, of which 192 were selected for a full content-body check. Of these, 112 studies were eventually deemed suitable for quantitative and qualitative analysis. Emphasis was placed on the spatial and temporal scales studied, the use of networks or graphs, and the granularity of the data used to evaluate the models. The models principally used to represent the spreading of outbreaks have been stochastic (55.36%), while the type of networks most frequently used are relationship networks (32.14%). The most common spatial dimension used is a region (19.64%) and the most used unit of time is a day (28.57%). Synthetic data as opposed to an external source were used in 51.79% of the papers. With regard to the granularity of the data sources, aggregated data such as censuses or transportation surveys are the most common. CONCLUSION: We identified a growing interest in the use of networks to represent disease transmission. We detected that research is focused on only certain combinations of the computational model, type of network (in both the expressive and the structural sense) and spatial scale, while the search for other interesting combinations has been left for the future.

A Novel Introgression Line Library Derived from a Wild Melon Gives Insights into the Genetics of Melon Domestication, Uncovering New Genetic Variability Useful for Breeding.

A collection of 30 melon introgression lines (ILs) was developed from the wild accession Ames 24297 (TRI) into 'Piel de Sapo' (PS) genetic background. Each IL carried an average of 1.4 introgressions from TRI, and the introgressions represented 91.4% of the TRI genome. Twenty-two ILs, representing 75% of the TRI genome, were evaluated in greenhouse (Algarrobo and Meliana) and field (Alcàsser) trials, mainly to study traits related to domestication syndrome such as fruit weight (FW) and flesh content (FFP), as well as other fruit quality traits as fruit shape (FS), flesh firmness (FF), soluble solid concentration (SSC), rind color and abscission layer. The IL collection showed an impressive variation in size-related traits, with FW ranging from 800 to 4100 g, reflecting the strong effect of the wild genome on these traits. Most of the ILs produced smaller fruits compared with PS; however, unexpectedly, the IL TRI05-2 produced bigger fruits, likely due to new epistatic interacions with the PS genetic background. In contrast, the genotypic effect for FS was smaller, and few QTLs with notable effects were detected. Interestingly, variability was also observed for FFP, FF and SSC, rind color and abscission layer formation. Genes in these introgressions are candidates for having been involved in melon domestication and diversification as well. These results confirm that the TRI IL collection is a very powerful tool for mapping traits of agronomic interest in melon, allowing the confirmation of previously reported QTLs and the identification of new ones to better understand the domestication process of this crop.

Meaningful time-related aspects of alerts in Clinical Decision Support Systems. A unified framework.

Alerts are a common functionality of clinical decision support systems (CDSSs). Although they have proven to be useful in clinical practice, the alert burden can lead to alert fatigue and significantly reduce their usability and acceptance. Based on a literature review, we propose a unified framework consisting of a set of meaningful timestamps that allows the use of state-of-the-art measures for alert burden, such as alert dwell time, alert think time, and response time. In addition, it can be used to investigate other measures that could be relevant as regards dealing with this problem. Furthermore, we provide a case study concerning three different types of alerts to which the framework was successfully applied. We consider that our framework can easily be adapted to other CDSSs and that it could be useful for dealing with alert burden measurement thus contributing to its appropriate management.

DNA Segregation in Enterobacteria.

DNA segregation ensures that cell offspring receive at least one copy of each DNA molecule, or replicon, after their replication. This important cellular process includes different phases leading to the physical separation of the replicons and their movement toward the future daughter cells. Here, we review these phases and processes in enterobacteria with emphasis on the molecular mechanisms at play and their controls.

Spotlight on hTERT Complex Regulation in Cutaneous T-Cell Lymphomas.

As a major cancer hallmark, there is a sustained interest in understanding the telomerase contribution to carcinogenesis in order to therapeutically target this enzyme. This is particularly relevant in primary cutaneous T-cell lymphomas (CTCL), a malignancy showing telomerase dysregulation with few investigative data available. In CTCL, we examined the mechanisms involved in telomerase transcriptional activation and activity regulation. We analyzed 94 CTCL patients from a Franco-Portuguese cohort, as well as 8 cell lines, in comparison to 101 healthy controls. Our results showed that not only polymorphisms (SNPs) located at the promoter of human telomerase reverse transcriptase (hTERT) gene (rs2735940 and rs2853672) but also an SNP located within the coding region (rs2853676) could influence CTCL occurrence. Furthermore, our results sustained that the post-transcriptional regulation of hTERT contributes to CTCL lymphomagenesis. Indeed, CTCL cells present a different pattern of hTERT spliced transcripts distribution from the controls, mostly marked by an increase in the hTERT ß+ variants proportion. This increase seems to be associated with CTCL development and progression. Through hTERT splicing transcriptome modulation with shRNAs, we observed that the decrease in the α-ß+ transcript induced a decrease in the cell proliferation and tumorigenic capacities of T-MF cells in vitro. Taken together, our data highlight the major role of post-transcriptional mechanisms regulating telomerase non canonical functions in CTCL and suggest a new potential role for the α-ß+ hTERT transcript variant.

Comparison of the levels of selected specific antibodies in the immunoglobulin G of colostrum versus milk and serum in dairy cows (Bos taurus).

Commercial products containing immunoglobulin G (IgG) sourced from colostrum, milk, and/or serum may be used to supplement or replace maternal colostrum in newborn dairy calves. To determine if antibody specificities in bovine milk and serum IgG differ from colostrum IgG, we sampled serum, colostrum (1 to 2 hours post-partum), and milk (day 5 post-partum) from 24 dairy heifers or cows. Specific antibodies [IgG class (H&L)] to 8 common pathogens were measured using enzyme-linked immunosorbent assays (ELISAs). Immunoglobin G1 and IgG2 subclass-specific ELISAs were performed for 3 of these pathogens. Colostrum-derived IgG contained more specific antibodies to rotavirus [IgG (H&L) and IgG1] and to IgG (H&L) of bovine respiratory syncytial virus (BRSV), bovine parainfluenza-3 virus (BPI3V), Staphylococcus aureus, Escherichia coli F5 (K99), and bovine coronavirus than milk IgG. Colostral IgG contained more antibodies to BRSV (IgG1), rotavirus (IgG1), and IgG (H&L) specific for BRSV, bovine herpesvirus-1 (BHV-1), BPI3V, E. coli F5 (K99), and Streptococcus uberis than serum IgG. Compared to serum, milk contained more IgG (H&L) antibody to BRSV, BHV-1, and BPI3V, IgG1-specific BRSV, and rotavirus. These data indicate that IgG derived from colostrum delivers more specific antibodies to these endemic pathogens of calves compared to IgG sourced from milk or serum. In addition, the IgG1 subclass predominates in milk and colostrum, and both deliver a similar spectrum of antibodies.

Les produits commerciaux contenant de l'immunoglobuline G (IgG) provenant du colostrum, du lait et/ou du sérum peuvent être utilisés pour compléter ou remplacer le colostrum maternel chez les veaux laitiers nouveau-nés. Pour déterminer si les spécificités des anticorps dans le lait de vache et les IgG sériques diffèrent des IgG du colostrum, nous avons prélevé du sérum, du colostrum (1 à 2 heures après le vêlage) et du lait (5 jours après le vêlage) de 24 génisses ou vaches laitières. Des anticorps spécifiques [classe IgG (H&L)] dirigés contre huit agents pathogènes courants ont été mesurés par dosages immuno-enzymatiques (ELISA). Des tests ELISA spécifiques aux sous-classes d'IG1 et d'IgG2 ont été effectués pour trois de ces agents pathogènes. Les IgG dérivées du colostrum contenaient plus d'anticorps spécifiques contre le rotavirus [IgG (H&L) et IgG1] et des IgG (H&L) contre le virus respiratoire syncytial bovin (BRSV), le virus parainfluenza bovin 3 (BPI3V), Staphylococcus aureus, Escherichia coli F5 (K99) et le coronavirus bovin que les IgG du lait. Les IgG du colostrum contenaient plus d'anticorps dirigés contre le BRSV (IgG1), le rotavirus (IgG1) et des IgG (H&L) spécifiques contre BRSV, l'herpèsvirus bovin-1 (BHV-1), le BPI3V, E. coli F5 (K99) et Streptococcus uberis que les IgG du sérum. Comparé au sérum, le lait contenait plus d'anticorps IgG (H&L) contre le BRSV, le BHV-1 et le BPI3V, des IgG1 spécifiques au BRSV et au rotavirus. Ces données indiquent que les IgG dérivées du colostrum fournissent des anticorps plus spécifiques contre ces agents pathogènes endémiques des veaux que les IgG provenant du lait ou du sérum. De plus, la sous-classe IgG1 prédomine dans le lait et le colostrum, et les deux fournissent un spectre similaire d'anticorps.(Traduit par Docteur Serge Messier).

Nanomedicine and nanobiotechnology applications of magnetoelectric nanoparticles.

Unlike any other nanoparticles known to date, magnetoelectric nanoparticles (MENPs) can generate relatively strong electric fields locally via the application of magnetic fields and, vice versa, have their magnetization change in response to an electric field from the microenvironment. Hence, MENPs can serve as a wireless two-way interface between man-made devices and physiological systems at the molecular level. With the recent development of room-temperature biocompatible MENPs, a number of novel potential medical applications have emerged. These applications include wireless brain stimulation and mapping/recording of neural activity in real-time, targeted delivery across the blood-brain barrier (BBB), tissue regeneration, high-specificity cancer cures, molecular-level rapid diagnostics, and others. Several independent in vivo studies, using mice and nonhuman primates models, demonstrated the capability to deliver MENPs in the brain across the BBB via intravenous injection or, alternatively, bypassing the BBB via intranasal inhalation of the nanoparticles. Wireless deep brain stimulation with MENPs was demonstrated both in vitro and in vivo in different rodents models by several independent groups. High-specificity cancer treatment methods as well as tissue regeneration approaches with MENPs were proposed and demonstrated in in vitro models. A number of in vitro and in vivo studies were dedicated to understand the underlying mechanisms of MENPs-based high-specificity targeted drug delivery via application of d.c. and a.c. magnetic fields. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Correlation tests between relative light unit and colony forming unit for improving adenosine triphosphate bioluminescence analysis in bacterial consolidation treatments on palaeontological heritage.

In this article bacterial carbonate mineralization treatments are proposed as a novel strategy for decayed fossils and palaeontological heritage conservation; specifically, by means of inoculation of Myxococcus xanthus, a bacterium of proven effectiveness in ornamental stone bioconsolidation. Bioconsolidation treatments can be very effective, stable, nontoxic, environmentally friendly, and chemically compatible with fossil heritage. The method reproduces what nature has been doing for millennia with fossils that have been permineralized by bacterial calcium carbonate precipitation. There is, however, some concern that bacterial inoculation could lead to the growth of undesirable microbiota, which could subsequently damage the fossil substrate. Because of this, the use of bacteria on heritage items must be meticulously monitored and analysis strategies should be carried out to detect bacteria viability during and after treatments. For this purpose, adenosine triphosphate assay is proposed in this article as a fast, affordable, portable, and easy-to-use system for conservators. as ATP assay results are relative and difficult to relate to colony forming unit, this study aims to improve their applicability by examining the correlation between ATP analysis and total viable bacteria count in the specific case of M. xanthus. This research provides reference and correlatable data to obtain an approximate estimation of M. xanthus viable bacterial colonies based on relative light unit data.

Business Process Model and Notation and openEHR Task Planning for Clinical Pathway Standards in Infections: Critical Analysis.

BACKGROUND: Clinical pathways (CPs) are usually expressed by means of workflow formalisms, providing health care personnel with an easy-to-understand, high-level conceptual model of medical steps in specific patient conditions, thereby improving overall health care process quality in clinical practice. From a standardized perspective, the business process model and notation (BPMN), a widely spread general-purpose process formalism, has been used for conceptual modeling in clinical domains, mainly because of its easy-to-use graphical notation, facilitating the common understanding and communication of the parties involved in health care. However, BPMN is not particularly oriented toward the peculiarities of complex clinical processes such as infection diagnosis and treatment, in which time plays a critical role, which is why much of the BPMN clinical-oriented research has revolved around how to extend the standard to address these special needs. The shift from an agnostic, general-purpose BPMN notation to a natively clinical-oriented notation such as openEHR Task Planning (TP) could constitute a major step toward clinical process improvement, enhancing the representation of CPs for infection treatment and other complex scenarios. OBJECTIVE: Our work aimed to analyze the suitability of a clinical-oriented formalism (TP) to successfully represent typical process patterns in infection treatment, identifying domain-specific improvements to the standard that could help enhance its modeling capabilities, thereby promoting the widespread adoption of CPs to improve medical practice and overall health care quality. METHODS: Our methodology consisted of 4 major steps: identification of key features of infection CPs through literature review, clinical guideline analysis, and BPMN extensions; analysis of the presence of key features in TP; modeling of relevant process patterns of catheter-related bloodstream infection as a case study; and analysis and proposal of extensions in view of the results. RESULTS: We were able to easily represent the same logic applied in the extended BPMN-based process models in our case study using out-of-the-box standard TP primitives. However, we identified possible improvements to the current version of TP to allow for simpler conceptual models of infection CPs and possibly of other complex clinical scenarios. CONCLUSIONS: Our study showed that the clinical-oriented TP specification is able to successfully represent the most complex catheter-related bloodstream infection process patterns depicted in our case study and identified possible extensions that can help increase its adequacy for modeling infection CPs and possibly other complex clinical conditions.

Living at the Wrong Time: Effects of Unmatching Official Time in Portugal and Western Spain.

Human circadian rhythmicity is subjected to the internal circadian clock, the sun and social clocks (official time, social/work schedules). The discrepancy among these clocks, as occurs when official time does not match its geographical time zone, may produce circadian disruption. Western Spain (GMT+1/+2) and Portugal (GMT0/+1) share similar longitudes (sun time) but have different official times. This provides a unique opportunity to evaluate the effects of official time on circadian rhythmicity and sleep in elderly and retired populations (with no remunerated duties presumed, although other social commitments may be present) at both locations. Although both populations slept enough for their age (7-8 h), circadian robustness (e.g., interdaily stability, relative amplitude) was greater in Portugal, especially during weekdays, while greater desynchronization (both body temperature vs. motor activity and body temperature vs. light exposure) tended to occur in the Spaniards. Once corrected by GMT0, meals took place later in Spain than in Portugal, especially as the day progresses, and a possible interplay between bed/meal timings and internal desynchronization was found. Our results point to the possible deleterious effect on circadian system robustness when official time is misaligned with its geographical time zone.

An Artificial Intelligence-Based Tool for Data Analysis and Prognosis in Cancer Patients: Results from the Clarify Study.

BACKGROUND: Artificial intelligence (AI) has contributed substantially in recent years to the resolution of different biomedical problems, including cancer. However, AI tools with significant and widespread impact in oncology remain scarce. The goal of this study is to present an AI-based solution tool for cancer patients data analysis that assists clinicians in identifying the clinical factors associated with poor prognosis, relapse and survival, and to develop a prognostic model that stratifies patients by risk. MATERIALS AND METHODS: We used clinical data from 5275 patients diagnosed with non-small cell lung cancer, breast cancer, and non-Hodgkin lymphoma at Hospital Universitario Puerta de Hierro-Majadahonda. Accessible clinical parameters measured with a wearable device and quality of life questionnaires data were also collected. RESULTS: Using an AI-tool, data from 5275 cancer patients were analyzed, integrating clinical data, questionnaires data, and data collected from wearable devices. Descriptive analyses were performed in order to explore the patients' characteristics, survival probabilities were calculated, and a prognostic model identified low and high-risk profile patients. CONCLUSION: Overall, the reconstruction of the population's risk profile for the cancer-specific predictive model was achieved and proved useful in clinical practice using artificial intelligence. It has potential application in clinical settings to improve risk stratification, early detection, and surveillance management of cancer patients.

Using the Diagnostic Odds Ratio to Select Patterns to Build an Interpretable Pattern-Based Classifier in a Clinical Domain: Multivariate Sequential Pattern Mining Study.

BACKGROUND: It is important to exploit all available data on patients in settings such as intensive care burn units (ICBUs), where several variables are recorded over time. It is possible to take advantage of the multivariate patterns that model the evolution of patients to predict their survival. However, pattern discovery algorithms generate a large number of patterns, of which only some are relevant for classification. OBJECTIVE: We propose to use the diagnostic odds ratio (DOR) to select multivariate sequential patterns used in the classification in a clinical domain, rather than employing frequency properties. METHODS: We used data obtained from the ICBU at the University Hospital of Getafe, where 6 temporal variables for 465 patients were registered every day during 5 days, and to model the evolution of these clinical variables, we used multivariate sequential patterns by applying 2 different discretization methods for the continuous attributes. We compared 4 ways in which to employ the DOR for pattern selection: (1) we used it as a threshold to select patterns with a minimum DOR; (2) we selected patterns whose differential DORs are higher than a threshold with regard to their extensions; (3) we selected patterns whose DOR CIs do not overlap; and (4) we proposed the combination of threshold and nonoverlapping CIs to select the most discriminative patterns. As a baseline, we compared our proposals with Jumping Emerging Patterns, one of the most frequently used techniques for pattern selection that utilizes frequency properties. RESULTS: We have compared the number and length of the patterns eventually selected, classification performance, and pattern and model interpretability. We show that discretization has a great impact on the accuracy of the classification model, but that a trade-off must be found between classification accuracy and the physicians' capacity to interpret the patterns obtained. We have also identified that the experiments combining threshold and nonoverlapping CIs (Option 4) obtained the fewest number of patterns but also with the smallest size, thus implying the loss of an acceptable accuracy with regard to clinician interpretation. The best classification model according to the trade-off is a JRIP classifier with only 5 patterns (20 items) that was built using unsupervised correlation preserving discretization and differential DOR in a beam search for the best pattern. It achieves a specificity of 56.32% and an area under the receiver operating characteristic curve of 0.767. CONCLUSIONS: A method for the classification of patients' survival can benefit from the use of sequential patterns, as these patterns consider knowledge about the temporal evolution of the variables in the case of ICBU. We have proved that the DOR can be used in several ways, and that it is a suitable measure to select discriminative and interpretable quality patterns.

Handling Time Constraints in Infection Clinical Pathways Using openEHR TP.

Clinical Pathways (CP) provide healthcare personnel with an easy-to-understand high level model of medical steps in specific patient conditions, thereby improving overall process quality in clinical practice. The emergence of new clinical-oriented standards such as openEHR Task Planning (TP) could pose a major step towards clinical process improvement, particularly in complex domains such as infection diagnosis and treatment, where time plays a critical role. In this work, we analyze the suitability of TP to successfully represent time constraints of common process patterns in infections, modelling some of the Catheter-Related Blood Stream Infection (CR-BSI) process patterns as a case study. Our research shows that TP is useful to represent time constraints of infection CPs, although minor improvements could increase its suitability not only for infection processes but for other time-related complex clinical scenarios.

Association of rhinitis with asthma prevalence and severity.

Asthma and rhinitis often co-exist in the same patient. Although some authors observed a higher prevalence and/or greater severity of asthma in patients with rhinitis, this view is not homogeneous and the debate continues. The aim of our study is to describe the prevalence of rhinitis in children and adolescents and to analyse their relationship with the prevalence of asthma. A multicentre study was conducted using the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC). The target population of the study was all those school children aged 6-7 and 13-14 years from 6 of the main health catchment areas of Galicia (1.9 million inhabitants). The schools required were randomly selected, and all children in the targeted age ranges were included. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) between asthma symptoms of the schoolchildren and rhinitis prevalence. The results were adjusted for parental smoking habits, maternal education level, cat and dog exposure, and obesity. A total of 21,420 valid questionnaires were finally obtained. Rhinitis was associated with a significant increase in the prevalence of asthma in both age groups. The highest OR were 11.375 for exercise induced asthma (EIA) for children with recent rhinoconjunctivitis and 9.807 for children with recent rhinitis in 6-7 years old group. The prevalence OR's are higher in EIA and severe asthmatics. Rhinitis in children and adolescents is associated with a higher prevalence and severity of asthma.