Toward a view-oriented approach for aligning RDF-based biomedical repositories.

INTRODUCTION: This article is part of the Focus Theme of METHODS of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". BACKGROUND: The need for complementary access to multiple RDF databases has fostered new lines of research, but also entailed new challenges due to data representation disparities. While several approaches for RDF-based database integration have been proposed, those focused on schema alignment have become the most widely adopted. All state-of-the-art solutions for aligning RDF-based sources resort to a simple technique inherited from legacy relational database integration methods. This technique - known as element-to-element (e2e) mappings - is based on establishing 1:1 mappings between single primitive elements - e.g. concepts, attributes, relationships, etc. - belonging to the source and target schemas. However, due to the intrinsic nature of RDF - a representation language based on defining tuples < subject, predicate, object > -, one may find RDF elements whose semantics vary dramatically when combined into a view involving other RDF elements - i.e. they depend on their context. The latter cannot be adequately represented in the target schema by resorting to the traditional e2e approach. These approaches fail to properly address this issue without explicitly modifying the target ontology, thus lacking the required expressiveness for properly reflecting the intended semantics in the alignment information. OBJECTIVES: To enhance existing RDF schema alignment techniques by providing a mechanism to properly represent elements with context-dependent semantics, thus enabling users to perform more expressive alignments, including scenarios that cannot be adequately addressed by the existing approaches. METHODS: Instead of establishing 1:1 correspondences between single primitive elements of the schemas, we propose adopting a view-based approach. The latter is targeted at establishing mapping relationships between RDF subgraphs - that can be regarded as the equivalent of views in traditional databases -, rather than between single schema elements. This approach enables users to represent scenarios defined by context-dependent RDF elements that cannot be properly represented when adopting the currently existing approaches. RESULTS: We developed a software tool implementing our view-based strategy. Our tool is currently being used in the context of the European Commission funded p-medicine project, targeted at creating a technological framework to integrate clinical and genomic data to facilitate the development of personalized drugs and therapies for cancer, based on the genetic profile of the patient. We used our tool to integrate different RDF-based databases - including different repositories of clinical trials and DICOM images - using the Health Data Ontology Trunk (HDOT) ontology as the target schema. CONCLUSIONS: The importance of database integration methods and tools in the context of biomedical research has been widely recognized. Modern research in this area - e.g. identification of disease biomarkers, or design of personalized therapies - heavily relies on the availability of a technical framework to enable researchers to uniformly access disparate repositories. We present a method and a tool that implement a novel alignment method specifically designed to support and enhance the integration of RDF-based data sources at schema (metadata) level. This approach provides an increased level of expressiveness compared to other existing solutions, and allows solving heterogeneity scenarios that cannot be properly represented using other state-of-the-art techniques.

p-medicine: A Medical Informatics Platform for Integrated Large Scale Heterogeneous Patient Data.

Secure access to patient data is becoming of increasing importance, as medical informatics grows in significance, to both assist with population health studies, and patient specific medicine in support of treatment. However, assembling the many different types of data emanating from the clinic is in itself a difficulty, and doing so across national borders compounds the problem. In this paper we present our solution: an easy to use distributed informatics platform embedding a state of the art data warehouse incorporating a secure pseudonymisation system protecting access to personal healthcare data. Using this system, a whole range of patient derived data, from genomics to imaging to clinical records, can be assembled and linked, and then connected with analytics tools that help us to understand the data. Research performed in this environment will have immediate clinical impact for personalised patient healthcare.

Relationship of dehydroepiandrosterone sulfate with overweight and insulin sensitivity in 12-16-year-old Spanish children.

DHEA-S is the most abundant steroid hormone in human circulation. Although a relationship of DHEA-S with obesity-related diseases has been reported, the metabolic role of this hormone remains unclear, particularly in children. In our study, we have investigated the relationship of DHEA-S levels with anthropometric variables, insulin, HOMA, and free fatty acids in adolescents. The study sample included 812 healthy 12-16-year-old children (383 boys and 429 girls). Plasma DHEA-S was determined by RIA, insulin concentrations by IRMA, and free fatty acids by using a commercial kit. Insulin resistance was estimated using the HOMA index. No significant differences in plasma DHEA-S levels were found between sexes. DHEA-S levels in overweight children were significantly higher than in normal-weight children. DHEA-S levels were significantly correlated with weight and BMI after adjusting for age. Significant positive correlations between DHEA-S and free fatty acids levels were found after adjusting for age and BMI, particularly in boys, but not between DHEA-S levels and insulin or HOMA in either gender. DHEA-S levels in 12-16-year-old children are correlated with weight and BMI independently of age. We failed to find any association between DHEA-S and insulin levels, but we did find a -significant correlation between DHEA-S and free fatty acids levels, suggesting that its association with free fatty acids may be related to the onset of the association of DHEA-S with insulin resi-stance.

[Assessment of overweight from prepuberty to adolescence]. / Valoración de la evolución temporal del sobrepeso desde la edad prepuberal hasta la adolescencia.

OBJECTIVE: To examine whether prepubertal overweight continues into adolescence, and to evaluate if this progression over time differs by sex. METHODS: The sample population consisted of 179 healthy boys and 206 girls on whom anthropometric data were assessed at 6-8 years and 13-16 years of age. The assessment of overweight was performed according to the cut-offs points of the International Obesity Task Force. RESULTS: From baseline to follow-up, the percentage of participants who were overweight increased from 23% to 29.2% in males, and decreased from 32.6% to 21.4% in females. Baseline weight was significantly correlated (P<.01) with follow-up weight in both males (r=0.78) and females (r=0.68). Weight and BMI at 6-to-8 years- old explained percentages of variation of weight and BMI at 13-to-16 years-old, higher in boys than in girls (64.1% and 44.1%, respectively, for weight; 53.5% and 39.9%, respectively, for BMI). A total of 75% of the participants remained in the same weight category. CONCLUSION: The prevalence of overweight in adolescence decreased in girls. The weight and BMI at prepubertal age account for a significant percentage of the variation in weight and BMI in adolescence. This percentage is higher in males than in females.

Nanoinformatics: developing new computing applications for nanomedicine.

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended "nanotype" to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

Association of the Q223R polymorphism with age at menarche in the leptin receptor gene in humans.

Although genetics clearly influences the onset of menarche, the association of age at menarche (AAM) with variants in genes related to energy homeostasis remains unexplored. Our aim was to analyze the relationship of the Q223R polymorphism in the leptin receptor gene (LEPR(Q223R)) with AAM in a population-based sample of healthy pubertal girls. The study included 338 Spanish girls aged between 11 and 17 yr. Data were collected on AAM. The Q223R polymorphism in LEPR was detected by TaqMan allelic discrimination assays. Girls carrying the RR genotype had a significantly younger AAM (11.5 yr) than those carrying the QR (11.9 yr) or QQ (12.0 yr) genotype (P < 0.05). Furthermore, we found a significantly higher frequency of the RR genotype in girls with an AAM of 11 yr or younger than in girls with an AAM older than 12 yr (23.9% vs. 7.8%, χ(2) = 11.17, P = 0.0008). Also, the RR genotype frequency in girls with an AAM between 11 and 12 yr was significantly higher than in girls with an AAM older than 12 yr (16.8% vs. 7.8%, χ(2) = 3.97, P = 0.0046). The Q223R polymorphism in the LEPR gene is associated with variations in AAM among Spanish girls, with the RR genotype being related to earlier onset.

Sex-specific association between leptin receptor polymorphisms and leptin levels and BMI in healthy adolescents.

AIM: To examine the relationship of three common polymorphisms in the leptin receptor (LEPR) gene, implicated in the regulation of body weight, with leptin levels and obesity-related phenotypes in a population-based sample of healthy pubertal children in Spain. METHODS: The study included 806 boys and girls aged 12-16 whose anthropometrical data and body composition were recorded. Serum leptin levels were determined by ELISA. The LEPR Q223R, K109R and K656N polymorphisms were determined by TaqMan® allelic discrimination assays. RESULTS: When analysing the Q223R polymorphism, we observed that female carriers of the RR genotype had significantly higher plasma leptin levels (18.2 vs. 15.1 ng/mL p = 0.016) and significantly higher mean BMI values (22.5 vs. 21.3 Kg/m² p = 0.032) than QR carriers. Furthermore, the frequency of the RR genotype in overweight-obese girls was significantly higher than that found in normal-weight girls. No significant differences were observed in boys. Neither boys nor girls showed significant differences when comparing leptin levels, anthropometric variables or body composition by K109R or K656N genotype. CONCLUSION: The fact, that the Q223R polymorphism in the LEPR gene is significantly associated with leptin levels and BMI only in girls, suggests a sex-specific influence of this polymorphism on these variables.

Trombosis mesentérica y accidente cereborvascular hemorrágico en pacientes con síndrome urémico hemolítico enteropático / Mesenteric thrombosis and hemorrhagic cerebrovascular accidente in patients with enteropatic hemolytic uremic syndrome

Se presentan 2 niños con síndrome urémico hemolítico asociado a diarrea,el primero con accidente cerebral vascular,con extenso sangrado occipital y el segundo debutó con trombosis de arteria mesentérica que requirió una urgente resección de íleon terminal hasta la unión rectosigmoidea.Ambos pacientes padecieron insuficiencia renal grave y tuvieron buena evolución clínica posterior

[Temporal evolution of tuberculosis and human immunodeficiency virus infection in a population cared for in a hospital in Málaga]. / Evolución temporal de la tuberculosis e infección por el virus de la inmunodeficiencia humana en la población atendida por un hospital de Málaga.

BACKGROUND: We have studied the incidence of tuberculosis++ disease, HIV infection and their association during a period of 6 years using samples analysed in a third level hospital laboratory. MATERIAL AND METHOD: 21,242 samples for mycobacteria and 63,425 for HIV antibodies were analysed between 1993 and 1998. The protocol used for mycobacteria consisted of Lowenstein-Jensen, hemoculture, biochemical tests for identification and DNA probe. The diagnosis of HIV was performed using screening with mix EIA HIV 1 + 2, confirmed with Western-blot. Spearman coefficient correlation was used for study of tendency. RESULTS: 1,613 samples (7.5%) positive for mycobacteria from 566 patients (98 females and 428 males) aging between 31 and 40 years (46.9%) were detected. The highest incidence for tuberculosis was observed in 1995 (49.2 x 10(5) and was followed by a decreasing linear tendency. Mycobacterium tuberculosis (96%) and M. bovis (2.7%) were most frequent agents. 2,295 samples (3.6%) showed anti-HIV (406 females and 1,889 males). 54.1% of the infected patients belonged to the age interval 21 to 40 years. The highest incidence was observed in 1994 and was followed by a significant decrease (p < 0.05). The percentage of patients co-infected with tuberculosis-HIV was 39.7% with a maximum in 1995 followed by a linear decrease. CONCLUSIONS: The incidence of both infections and co-infection was very high in the first triennium and was followed by a progressive decrease. The decrease of HIV preceded tuberculosis. The result suggest a possible epidemiological correlation between both infections.

Metabolic acidosis and coma due to an overdose of nalidixic acid.

A case of severe metabolic acidosis and coma after taking 28 g of nalidixic acid is described. After administration of 600 mEq of sodium bicarbonate the patient developed a respiratory alkalosis with secondary tetany. She recovered her state of consciousness nine hours later and the acid-base disturbance resolved after sixty hours.

[Acute abdomen due to hemoperitoneum as the first manifestation of a liver tumor. Report of four cases (author's transl)]. / Abdomen agudo por hemoperitoneo como primera manifestación de un tumor hepático. A propósito de cuatro casos.

Four cases of spontaneous acute hemoperitoneum due to rupture of a liver tumor are presented. The resulting acute abdomen was the first manifestation of the neoplasia. The four tumors corresponded histopathologically to a cavernous hemangioma, a bening adenoma related to anabolizing androgens, and two hepatocarcinomas in cirrhotic livers. All of the patients presented abdominal pain and shock, the characteristics of which are described in this report. One of the patients died due to cardiac arrest before surgical treatment. Emergency surgery was performed on the other three, consisting of left hepatic lobectomy and ligature of the hepatic artery for the hemengioma, and segmented hepatectomy for the adenoma and the hepatocarcinoma. Only the patient with benign tumor survived. Lastly, the authors review the literature, commenting on the clinical, physiopathologic, therapeutic, and prognostic aspects.