Análisis bibliométrico de la producción científica española en Enfermedades Infecciosas y en Microbiología / Bibliometric analysis of the Spanish scientific production in Infectious Diseases and Microbiology

INTRODUCCIÓN: El análisis bibliométrico de la producción y repercusión de los documentos por áreas de conocimiento es un indicador cuantitativo y cualitativo de la actividad investigadora realizada en ese campo. El objetivo de este artículo es conocer la contribución de las instituciones españolas a la investigación en Enfermedades Infecciosas y en Microbiología en los últimos años. MATERIAL Y MÉTODOS: Se analizaron los documentos publicados en las revistas incluidas en las categorías «Infectious Diseases» y «Microbiology» de la Web of Science (Science Citation Index Expanded) de la ISI Web of Knowledge desde el año 2000 al 2013. RESULTADOS: En Enfermedades Infecciosas, España ocupó la cuarta posición a nivel mundial y contribuyó con el 5,7% de los 233.771 documentos publicados en esta especialidad. En Microbiología, España se situó en la sexta posición, con un porcentaje de producción del 5,8% de los 149.269 documentos de la categoría. La producción española aumentó a lo largo del período de estudio, tanto en Enfermedades Infecciosas como en Microbiología, pasando de 325 y 619 documentos en el año 2000 a 756 y 1.245 documentos en el año 2013, con una tasa de crecimiento del 131 y del 45,8%, respectivamente. La revista donde se publicó el mayor número de documentos fue Enfermedades Infecciosas y Microbiología Clínica. El 8,6 y el 8,2% de los documentos publicados en las categorías de Enfermedades Infecciosas y Microbiología, respectivamente, fueron el resultado de colaboraciones internacionales, especialmente con instituciones de Estados Unidos de América. El «índice h» fue de 116 en Enfermedades Infecciosas y de 139 en Microbiología, situando a España en la quinta posición en ambas categorías dentro de los países de la Unión Europea. CONCLUSIONES: En los últimos años la investigación española en Enfermedades Infecciosas y Microbiología ha alcanzado un buen nivel en producción y visibilidad internacional, alcanzando una posición de liderazgo mundial

INTRODUCTION: The bibliometric analysis of production and impact of documents by knowledge area is a quantitative and qualitative indicator of research activity in this field. The aim of this article is to determine the contribution of Spanish research institutions in Infectious Diseases and Microbiology in recent years. MATERIAL AND METHODS: Documents published in the journals included in the categories "Infectious Diseases" and "Microbiology" of the Web of Science (Science Citation Index Expanded) of the ISI Web of Knowledge from the year 2000-2013 were analysed. RESULTS: In Infectious Diseases, Spain ranked fourth worldwide, and contributed 5.7% of the 233,771 documents published in this specialty. In Microbiology, Spain was in sixth place with a production rate of 5.8% of the 149,269 documents of this category. The Spanish production increased over the study period, both in Infectious Diseases and Microbiology, from 325 and 619 documents in 2000 to 756 and 1245 documents in 2013, with a growth rate of 131% and 45.8%, respectively. The journal with the largest number of documents published was Enfermedades Infecciosas y Microbiología Clínica, with 8.6% and 8.2% of papers published in the categories of Infectious Diseases and Microbiology, respectively, and was the result of international collaborations, especially with institutions in the United States. The "index h" was 116 and 139 in Infectious Diseases and Microbiology, placing Spain in fifth place in both categories within countries of the European Union. CONCLUSIONS: In recent years, Spanish research in Infectious Diseases and Microbiology has reached a good level of production and international visibility, reaching a global leadership position

Evaluación de técnicas inmunológicas in vitro para el diagnóstico de alergias: metanálisis 2000-2012 / Evaluation of techniques in vitro immune to the diagnosis of allergy: Meta-analysis 2000-2012

Fundamentos: Las alergias presentan elevada prevalencia, afectan a todos los grupos etarios, generan impactos negativos sobre los sistemas de salud, educativo y económico. Se desconoce la utilidad diagnóstica de las pruebas de tamización. El objetivo del estudio fue evaluar la validez, el desempeño, la seguridad y la efectividad diagnóstica de las técnicas inmunológicas in vitro para alergias Métodos: Revisión sistemática con metaanálisis. Se aplicó una estrategia de búsqueda de estudios en Pubmed, Sciencedirect y Wiley con los términos de búsqueda activation basophil test, lymphocyte transformation test, especific IgE immunoassay. Período estudiado: 2000-2012. Se determinó la reproducibilidad de la selección, extracción y evaluación de la calidad de los artículos. Se calculó sensibilidad, especificidad, cocientes de probabilidad, valores predictivos, proporción de resultados falsos, exactitud, razón de odds, índice J de Youden y curva ROC con los software Meta-DiSc(es) y Epidat 3.0 Resultados: Se incluyeron 18 estudios con 3.520 individuos, 58% enfermos y 42% sanos. La activación de basófilos presentó sensibilidad del 78% (IC95%:74-81), especificidad 95% (IC95%:83-100), cociente de probabilidad positivo 9,9 (IC95%:6,8-14,4) y negativo de 0,20 (IC95%:0,13-0,30), OR diagnóstica de 70,8 (IC95:40,2-124,8) y un área bajo la curva de 0,97. En la inmunoglobulina E específica la sensibilidad fue 72% (IC95%:69-75), especificidad 90% (IC95%:88-92), cociente de probabilidad positivo 12,9 (IC95%:4,0-41,6) negativo 0,32 (IC95%:0,23-0,43), OR diagnóstica 41,6 (IC95%:11,6-148,9) y área bajo la curva 0,87 Conclusión: Se evidenció que la activación de basófilos y la IgE específica son pruebas útiles en el diagnóstico de alergias (AU)

Background: Allergies have high prevalence, affecting all age groups, generate negative impacts on health, educational and economic systems, and they are unknown the diagnostic utility of screening tests. The objective of the study was to evaluate the validity, performance, safety and diagnostic efficiency of in vitro immunological techniques for allergies, 2000-2012 Methods: Systematic review with meta-analysis. We applied a search strategy studies in PubMed, Sciencedirect and Wiley, with search terms activation basophil test, lymphocyte transformation test, especific IgE immunoassay. We determined the reproducibility of the selection, extraction and quality assessment of articles. We calculated sensitivity, specificity, likelihood ratios, predictive values, proportion of false, accuracy, odds ratio, Youden index J and ROC curve in Meta-DiSc(es) and Epidat 3.0. software Results: We included 18 studies with 3520 individuals, 58% patients and 42% healthy. Activation of basophils showed sensitivity of 78% (95% CI :74-81), specificity 95% (95% CI: 83-100), positive likelihood ratio 9.9 (95% CI: 6.8 to 14.4) and negative of 0.20 (95% CI = 0.13 to 0.30) a diagnostic OR 70.8 (IC95: 40.2 to 124.8) and area under the curve of 0.97. In specific immunoglobulin E sensitivity was 72% (95% CI: 69-75), specificity 90% (95% CI : 88-92), positive likelihood ratio 12.9 (95% CI = 4.0 to 41.6) negative 0.32 (95% CI:0.23-0.43), diagnostic OR 41.6 (95% CI :11.6 to 148.9) and area under the curve 0.87 Conclusion: We showed that activation of basophils and specific IgE are useful tests for diagnosing allergies (AU)

A computational framework for the analysis of peptide microarray antibody binding data with application to HIV vaccine profiling.

We present an integrated analytical method for analyzing peptide microarray antibody binding data, from normalization through subject-specific positivity calls and data integration and visualization. Current techniques for the normalization of such data sets do not account for non-specific binding activity. A novel normalization technique based on peptide sequence information quickly and effectively reduced systematic biases. We also employed a sliding mean window technique that borrows strength from peptides sharing similar sequences, resulting in reduced signal variability. A smoothed signal aided in the detection of weak antibody binding hotspots. A new principled FDR method of setting positivity thresholds struck a balance between sensitivity and specificity. In addition, we demonstrate the utility and importance of using baseline control measurements when making subject-specific positivity calls. Data sets from two human clinical trials of candidate HIV-1 vaccines were used to validate the effectiveness of our overall computational framework.

Monthly variation of Dermatophagoides allergens and its influence on respiratory allergy in a high altitude environment (Quito, 2800ma.s.l. in Andean Ecuador)

Background: Seasonal variation of Dermatophagoides allergens and its influence in allergic respiratory airway diseases has not been investigated in Andean cities. The objective of this study was to evaluate those parameters in a city located in the Andean mountains. Methods: Der p1 and Der f1 were measured in dust samples from mattresses in 13 houses in Quito (2800m above sea level). Samples were collected monthly from August 2004 to July 2005. Patients presenting to a local outpatient allergy clinic with asthma and rhinitis and isolated allergy to Dermatophagoides were analysed to determine if a correlation existed between seasonal Der allergen levels and the number of patients presenting with allergies. Results: High levels of dust mites and humidity were observed throughout the year. The highest geometrical mean values of allergens were detected in April (Der p1, 10.15ìg/g) and May (Der f1, 13.03ìg/g), whilst the lowest levels were detected in August (Der p1, 4.26ìg/g), and September (Der f1, 1.4ìg/g). Of the 361 patients examined, 182 were allergic to Dermatophagoides, (45.6% asthmatics, 97.8% rhinitics, and 43.4% with both diseases). Patient presentation spiked in August, and from February to May. However, there was not a significant correlation between mite allergen concentrations and humidity or the number of patients presenting with allergies. Conclusions: Dust samples from mattresses in Quito revealed high concentrations of Der p1 and Der f1. We observed a trend towards increased presentation of asthmatic and rhinitic patients in the months with highest levels of allergens (AU)

Simultaneous detection of many T-cell specificities using combinatorial tetramer staining.

The direct detection of antigen-specific T cells using tetramers of soluble peptide-major histocompatibilty complex (pMHC) molecules is widely used in both basic and clinical immunology. However, the number of specificities that can be assessed simultaneously has been a major limitation. Here we describe and validate a method using combinations of fluorescent pMHC tetramers to simultaneously detect and enrich for many (>or=15) T-cell specificities in a single human blood sample.

A new era for innate immunity

In recent years our concept of the non-specific nature of innate immunity has changed following the identification of a network of germline-encoded receptors that recognise with substantial specificity molecular motifs of microorganisms and many other cues produced during tissue injury. Stimulation of these innate sensors by their specific ligands triggers signalling pathways that result in the activation of innate effector mechanisms as well as the priming of naive lymphocytes for the type of response that must be induced. These events culminate in the generation of an immune response appropriately adapted to the damage that has occurred. These new insights into innate immunity herald an entirely new era in the understanding of the molecular events that initiate and drive a host-protective response, changing many concepts about susceptibility to infections and providing greater insight into the underlying inflammatory pathology of other diseases. Targeted manipulation of innate immunity has enormous potential for the development of new vaccines and innovative therapies for the treatment of diseases such as infections, cancer, allergy, autoimmunity and autoinflammatory diseases. This article provides an overview of current trends in the field of innate immunity and its role in the control of infection and disease

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A guide to modern statistical analysis of immunological data.

BACKGROUND: The number of subjects that can be recruited in immunological studies and the number of immunological parameters that can be measured has increased rapidly over the past decade and is likely to continue to expand. Large and complex immunological datasets can now be used to investigate complex scientific questions, but to make the most of the potential in such data and to get the right answers sophisticated statistical approaches are necessary. Such approaches are used in many other scientific disciplines, but immunological studies on the whole still use simple statistical techniques for data analysis. RESULTS: The paper provides an overview of the range of statistical methods that can be used to answer different immunological study questions. We discuss specific aspects of immunological studies and give examples of typical scientific questions related to immunological data. We review classical bivariate and multivariate statistical techniques (factor analysis, cluster analysis, discriminant analysis) and more advanced methods aimed to explore causal relationships (path analysis/structural equation modelling) and illustrate their application to immunological data. We show the main features of each method, the type of study question they can answer, the type of data they can be applied to, the assumptions required for each method and the software that can be used. CONCLUSION: This paper will help the immunologist to choose the correct statistical approach for a particular research question.

Statistical analysis of CDR3 length distributions for the assessment of T and B cell repertoire biases.

Complementarity-determining region 3 (CDR3) length distribution analysis explores the diversity of the T cell receptor (TCR) and immunoglobulin (Ig) repertoire at the transcriptome level. Studies of the CDR3, the most hypervariable part of these molecules, have been frequently used to identify recruitment of T and B cell clones involved in immunological responses. CDR3 length distribution analysis gives a clear perception of repertoire variations between individuals and over time. However, the complexity of CDR3 length distribution patterns and the high number of possible repertoire alterations per individual called for the development of robust data analysis methods. The goal of these methods is to identify, quantify and statistically assess differences between repertoires so as to offer a better diagnostic or predictive tool for pathologies involving the immune system. In this review we will explain the benefit of analyzing CDR3 length distribution for the study of immune cell diversity. We will start by describing this technology and its associated data processing, and will subsequently focus on the statistical methods used to compare CDR3 length distribution patterns. Finally, we will address the various methods for assessing CDR3 length distribution gene signatures in pathological states.

An automated multi well cell track system to study leukocyte migration.

Design of automated image processing systems to determine migration characteristics of individual cells is not trivial. Every test sample requires separate recording and the analysis of individual cell tracks in two- or three-dimensional migration systems by time-lapse microscopy is extremely laborious. Here, we describe a new Automated Cell Track System (ACTS). In addition to contrast differences, which are used by existing analysis systems, the ACTS algorithms recognize cells on the basis of morphological similarities in successive images and adapt to the continuous shape changes of individual cells during migration. The system facilitates simultaneous analysis of multiple cells and the measurement of multiple wells in one single experiment. We validated the system studying HSB-2 T cell migration in standard 96-well microtiter plates coated with ICAM-1-Fc protein or control CD14-Fc protein. Migration of HSB-2 T cells on ICAM-1-Fc is Leukocyte Function-associated Antigen-1 (LFA-1)-mediated and both the number and the speed of migrating cells depend on the ICAM-1-Fc concentration. We show that automated analysis of the migration data yields similar results as manual analysis, but in a fraction of the time. We conclude that this system is extremely well suited to precisely monitor the migratory behavior of individual cells. The analysis of multiple wells in parallel makes this set-up appropriate in high throughput screening in which multiple components are simultaneously tested for their effect on cell migration.

A systematic comparison of methods to measure HIV-1 specific CD8 T cells.

Several methods are now available to evaluate the frequencies of virus-specific CD8 T cells but require a systematic comparison to help at choosing the best strategy for evaluation. First, we compared the ELISpot-IFNgamma assay, intracellular IFNgamma staining and HLA class I tetramer-binding assay to quantify the HIV-specific CD8 T cells. Second, we determined the frequency of recognition of HIV antigens and evaluated whether the mode of antigen presentation might influence the results: We compared HIV antigen presentation in the same ELISpot-IFNgamma assays by using recombinant vaccinia viruses (rVVs) encoding for HIV-LAI Gag, Pol, Env, Nef, Tat and Vif proteins, or a panel of 49 synthetic 8-11 amino acid length peptides tested either individually or pooled. Third, we compared the antigens recognized by memory CTL analysis using chromium release assay (CRA) on CTL lines and by effector CD8 cell analysis using ELISpot assay. Our results show that: (1) Flow cytometry and ELISpot assay measuring IFNgamma production give the same frequency of HIV-specific CD8 T cells; (2) tetramer-binding assay detects more HIV-specific CD8 T cells than other methods; (3) pools of optimal peptides and sum frequencies of individual optimal peptides give similar results in ELISpot assay; (4) ELISpot assays using peptides are more sensitive than those using rVV; and (5) CRA and ELISpot assay when using rVV provide a comparable profile of HIV antigen recognition by memory CTLs (CRA) and effector CTLs (ELISpot) in two thirds cases. These results have important implications for the choice of immunological methods to evaluate CD8 T cells responses to vaccines.

A cost-effective analysis of the optimum number of stool specimens collected for immunochemical occult blood screening for colorectal cancer.

This study was carried out to assess, from the viewpoint of cost-effectiveness, the optimum number of faecal specimens to collect for use in immunochemical occult blood testing as a means of screening for colorectal cancer. 3300 asymptomatic individuals were subjects of this study. They gave samples for an immunochemical faecal occult blood test, monohaem and colonoscopy was carried out during a medical check-up. For evaluation of the optimum number of sampling specimens, the results of the first day of sampling, those of the first and second days, and those of samples taken for 3 consecutive days were considered as the single-day method, the 2-day method and the 3-day method respectively. The average cost to detect 1 patient with colorectal cancer, the detection rate and the false-positive rate of these three faecal sample collection methods were evaluated. The average costs for one cancer case detected were calculated as $3,630.68 for the single-day method, $3,350.65 for the 2-day method and $4,136.36 for the 3-day method, respectively. The detection rate and the false-positive rate were calculated as 47 and 3.5% for the single-day method, 82 and 4.7% for the 2-day method and 88 and 5.3% for the 3-day method, respectively. This detection rate was significantly different between the single- and the 2-day methods, as well as between the single- and the 3-day methods (P<0. 05). No significant differences in the false-positive rate amongst the three testing methods were observed. This analysis suggests that a 2-day faecal collection method is recommended for immunochemical occult blood screening by Monohaem from the aspects of cost-effectiveness and diagnostic accuracy.

Detection of Mycobacterium avium subsp. paratuberculosis in infected tissues by new species-specific immunohistological procedures.

We have previously described the cloning and sequencing of a gene portion coding for the terminal part of a 34-kDa protein of Mycobacterium avium subsp. paratuberculosis, the etiological agent of Johne's disease (P. Gilot, M. De Kesel, L. Machtelinckx, M. Coene, and C. Cocito, J. Bacteriol. 175:4930-4935, 1993). The recombinant polypeptide (a362) carries species-specific B-cell epitopes which do not cross-react with other mycobacterial pathogens (M. De Kesel, P. Gilot, M.-C. Misonne, M. Coene, and C. Cocito, J. Clin. Microbiol. 31:947-954, 1993). The present work describes the preparation of polyclonal and monoclonal antibodies directed against a362 and the use of these immunoglobulins for histopathological diagnosis of Johne's disease. The new immunohistological procedures herewith detailed proved to be able to identify M. avium subsp. paratuberculosis antigens in the intestinal tissues and lymph nodes of cattle affected by either the paucibacillary or pluribacillary form of the disease. They yielded negative responses not only with healthy animals but also with those affected by tuberculosis (Mycobacterium bovis). Both immunohistological procedures proved to be as sensitive as or more sensitive than Ziehl-Neelsen staining and, in addition, to be endowed with species specificity.

[National study of screening practices for hepatitis C among hemodialysis patients. Hepatitis Group]. / Etude nationale des pratiques de dépistage de l'hépatite C chez les patients hémodialysés. Hepatitis Group.

French and American consensus conferences on hepatitis C confirmed the burden of that disease, especially in high risk populations. In France, the seroprevalence of HCV is about 20% among haemodialysed patients. This study aimed at describing the French screening practices in haemodialysed patients. In 1995, 1213 self-administered questionnaires were sent to nephrologists working in 715 dialysis units. The response rate was 48% (585/1213) and 485 questionnaires were analysed. In 98% of questionnaires nephrologists answered that they prescribed screening test. Routine screening with alanine amino-transferase (ALT) was reported in 98% of questionnaires, usually once a month (57%) or four times a year (23%). Routine anti-HCV serology was reported by 96%, usually once (28%) or twice (46%) a year. The two main annual strategies combining ALT and anti-HCV serology were 12 ALT and 2 serologies (21%), or 12 ALT and 1 serology (14%) per year. HCV RNA detection was reported mainly in the case of positive anti-HCV serology (70%). The study suggested heterogeneity in screening practices and revealed the need to determine the cost-effectiveness ratios of the various strategies.

Regression analysis of simulated radio-ligand equilibrium experiments using seven different mathematical models.

The objective of this study was to investigate the conditions for regression analysis of data from equilibrium experiments. One important issue was to recognize that Kd and the binding site concentration (A) are not of equal nature, although both are parameters in the regression analysis. Whereas Kd approximates to a true constant, A is subject to experimental variation due to pipetting errors and in solid-phase experiments also to uneven coating properties. While recognizing that the ideal assumptions for ordinary regression analysis are poorly satisfied, different regression models were evaluated by extensive simulations. It was first established by a 'worst case' investigation that a limited error (8%) in the dependent variable is not critical for the results obtained at curve-fitting to Langmuir's equation. Seven different equations were compared for the calculation of data representing a solid-phase equilibrium experiment with statistical but no systematic errors. All the equations are rearrangements of the law of mass action. In this setting the Scatchrd plot gave the best result, but also the double reciprocal and the Woolf plots worked well in weighted analysis. Langmuir's equation gave the best result of the 4 nonlinear regression models tested. The influence of one type of systematic error was also investigated. This assumed that 10% of the label was positioned on particles other than the functional ligand molecules. This systematic error was amplified, which resulted in a substantial bias. The calculated Kd-values varied slightly with the regression method used and were almost 24% too high in the best methods.

Encuesta inmunológica en la población infantil / Immunologic survey in children in Mexico city

Se presentan los resultados de la evaluación de la reacción de fijación en superficie aplicada al diagnóstico de infecciones por Salmonella Typhosa. Esta reacción a la luz de nuestros datos, demostró ser útil (con alto grado de especificidad) en la detección de anticuerpos contra S. thyphosa, existiendo sin embargo, reacciones cruzadas con salmonelas que poseen antígenos somáticos otras salmonelosis, shigelosis, o infecciones por Escherichia coli, tampoco se les encontró en 104 pacientes con diversos padecimientos infecciosos distintos de fiebre tifoidea. El 100 por ciento de 12 conejos inmunizados con S. typhosa presentó reacción de fijación en superficie positiva, así como el 99 por ciento de 102 niños con tifoidea comprobada bacteriológicamente. En este último grupo, la reacción se hizo positiva, en el 95 por ciento de los casos, desde la primera semana de evolución aparente del padecimiento y empezó a negativizarse a partir del segundo mes. Con la misma reacción se practicó investigación de anticuerpos contra S. typhosa en 2,698 niños aparentemente sanos residentes en el distrito Federal, provenientes de 3 estratos socioeconómicos. El 19.2 por ciento reveló tener anticuerpos, pero dicho porcentaje varió de acuerdo con las condiciones de saneamiento, del 7.5 por ciento en las zonas donde era satisfactorio, al 35.5 por ciento en donde era pésimo. La proporción de positivos aumentó con la edad, obteniéndose el mayor incremento a partir de los 6 años, edad en que entran a la escuela. Se fijan los límites de intensidad de la reacción de fijación en superficie, a partir de los cuales se le pueden dar valor diagnóstico en fiebre tifoidea. Esto se hizo con base a los resultados de la encuesta, tomando en cuenta el número de reactores positivos no tifoídicos, según la edad y el estrato socioeconómico

Screening panels of monoclonal antibodies using phage-displayed antigen.

A procedure is described to screen panels of hybridomas or purified monoclonal antibodies using antigen displayed on the surface of filamentous bacteriophage. In this system, samples containing murine monoclonal antibodies are incubated with phage-displayed antigen in microtiter plates coated with rabbit anti-mouse IgG, and bound antibody-phage complex is detected with horseradish peroxidase-sheep anti-phage M13 conjugate. The assay has been validated with a panel of 16 monoclonal antibodies directed against human plasminogen, using phage-displayed miniplasmin-(ogen) (amino acids Ala444 through Asn791 comprising kringle 5 and the proteinase domain of plasminogen) or microplasminogen (amino acids Ala543 through Asn791 comprising the proteinase domain). Six monoclonal antibodies were identified directed against miniplasminogen and miniplasmin; this was confirmed using a microtiter plate coated with antigens. One of these monoclonal antibodies (MA-42B12) did not react with microplasminogen, suggesting that its epitope is comprised within the kringle 5 domain. This test is rapid and sensitive (detecting 10-20 ng/ml of monoclonal antibody), and screening can be performed using phage-displayed zymogens or active enzymes or selected domains thereof. The procedure eliminates the need for large amounts of purified antigen for screening. Furthermore, immunization can be performed with partially purified antigen because only antibodies raised against the antigen of interest will be identified with the use of phage-displayed antigen. Therefore, this test may offer distinct advantages over the classical one-site enzyme-linked immunosorbent assay using antigen-coated microtiter plates.