ALK rearrangement in a selected population of advanced non small cell lung cancer patients. FISH and inmunohistochemistry diagnostic methods, prevalence and clinical outcomes

Anaplastic lymphoma kinase (ALK) rearrangements represents a new driver oncogenic event in non-small cell lung cancer (NSCLC). ALK positive patients account for a 1-7% of NSCLC patients. The objective of this study is to know the prevalence and clinical characteristics of ALK positive patients in a cohort of NSCLC patients and to compare inmunohistochemistry with D5F3 monoclonal antibody with gold standard method fluorescence in situ hybridation

Clinical application of differential time to positivity of blood cultures as a diagnostic method for catheter-related bloodstream infection.

La sospita de bacterièmia relacionada a catèter (BRC) necessita la retirada d’aquest, confirmant-se a posteriori només en un 15-25%. La diferencia en el temps de positivització d´ hemocultius (DTP) ha demostrat ser un mètode fiable per el diagnòstic de BRC evitant la retirada del catèter. Amb la intenció de comprovar la utilitat clínica de la DTP, l’hem comparada amb un mètode diagnòstic estàndard. Hem inclòs 133 pacients ingressats a una unitat de cures intensives portadors de catèters venosos centrals. 56 pacients s’han aleatoritzats. No hem trobat diferències significatives en quant a morbi-mortalitat en els 2 grups havent evitat 70% de retirada innecessària de catèters en el grup de DTP.

Tendències temporals de la mortalitat per càncer de fetge a Catalunya: periode 1983-2002 i projeccions pel 2005

Estudi elaborat a partir d’una estada al Finnish Cancer Registry a Helsinki, Finlandia entre setembre i novembre del 2006. Davant l’increment dels tumors hepàtics en països industrialitzats, s’avaluen les tendències temporals de la malaltia hepàtica a Catalunya durant el període 1983-2002 i s’estima la tendència futura a partir de l’any 2005. L’estudi s’ha basat en dades del Registre de Mortalitat de Catalunya i de l’Institut d’Estadística de Catalunya. La malaltia hepàtica inclou diverses tipologies de tumors hepàtics i la cirrosi hepàtica. Els models edad-període-cohort s’han emprat per estimar els efectes període de mortalitat i cohort de naixement. Els resultats han mostrat que les taxes de mortalitat per cirrosi han disminuït en ambdós sexes, exceptuant els homes d’entre els 35-50 anys, pels quals la mortalitat es mantingué estable. S’han observat increments en la mortalitat per carcinoma hepatocel•lular i en els tumors de vies biliars intrahepàtiques, mentre que les projeccions mostren estabilitat en la tendència d’aquestes malalties durant el període 2005-2009. Les tendències de la mortalitat per malaltia hepàtica constatades poden ser degudes a la implementació de teràpies noves, nous mètodes de diagnòstic, infecció pel virus de l’hepatitis C d’altres factors desconeguts.

Structured RNAs in the ENCODE selected regions of the human genome

Functional RNA structures play an important role both in the context of noncoding RNA transcripts as well as regulatory elements in mRNAs. Here we present a computational study to detect functional RNA structures within the ENCODE regions of the human genome. Since structural RNAs in general lack characteristic signals in primary sequence, comparative approaches evaluating evolutionary conservation of structures are most promising. We have used three recently introduced programs based on either phylogenetic–stochastic context-free grammar (EvoFold) or energy directed folding (RNAz and AlifoldZ), yielding several thousand candidate structures (corresponding to ∼2.7% of the ENCODE regions). EvoFold has its highest sensitivity in highly conserved and relatively AU-rich regions, while RNAz favors slightly GC-rich regions, resulting in a relatively small overlap between methods. Comparison with the GENCODE annotation points to functional RNAs in all genomic contexts, with a slightly increased density in 3′-UTRs. While we estimate a significant false discovery rate of ∼50%–70% many of the predictions can be further substantiated by additional criteria: 248 loci are predicted by both RNAz and EvoFold, and an additional 239 RNAz or EvoFold predictions are supported by the (more stringent) AlifoldZ algorithm. Five hundred seventy RNAz structure predictions fall into regions that show signs of selection pressure also on the sequence level (i.e., conserved elements). More than 700 predictions overlap with noncoding transcripts detected by oligonucleotide tiling arrays. One hundred seventy-five selected candidates were tested by RT-PCR in six tissues, and expression could be verified in 43 cases (24.6%).

Genome sequence of Plesiomonas shigelloides strain 302-73 (serotype O1)

Plesiomonas shigelloides, the only species of the genus, is an emergent pathogenic bacterium associated with human diarrheal and extraintestinal disease. We present the whole-genome sequence analysis of the representative strain for the O1 serotype (strain 302-73), providing a tool for studying bacterial outbreaks, virulence factors, and accurate diagnostic methods.

Hospital doctors' views and concerns about pharmacovigilance

Purpose: The aim of the study was to evaluate the opinions and concerns of hospital doctors about adverse drug reactions (ADRs) and pharmacovigilance. Methods: A qualitative study was undertaken using focus groups in sessions on pharmacovigilance activities conducted in thirteen clinical services of a tertiary university hospital. A total of 296 physicians participated in these sessions by giving their opinions or expressing their doubts about ADR and pharmacovigilance activities which were recorded by different observers and subsequently analysed. Results: Doctors remarked on: a) the importance, concern, frequency and specific types of ADRs that were observed in clinical practice; b) problems of clinical decision making related to the suspected ADRs; c) methods for improving detection and reporting ADRs; d) monitoring of specific ADRs or ADRs caused by specific drugs; e) and measures to prevent and minimize the risk of ADRs. Physicians expressed doubts related to: a) the basic concepts of ADRs; b) the methods of ADR identification and evaluation; c) the objectives and procedures of pharmacovigilance programmes; d) and the impact of pharmacovigilance activities. Conclusions: Hospital doctors believe that ADRs are a matter for concern in their daily clinical practice, and monitoring ADRs as well as measures for preventing the risk of ADRs are needed. Nevertheless, doctors have doubts about what an ADR is, the accuracy of diagnostic methods, the development of pharmacovigilance activities and their impact on clinical practice. Pharmacovigilance should be better explained through a continuous feedback and close relationship with hospital doctors.

Portafolio selection with skewness: a comparison of methods and a generalized two fund separation result

This contribution compares existing and newly developed techniques for geometrically representing mean-variances-kewness portfolio frontiers based on the rather widely adapted methodology of polynomial goal programming (PGP) on the one hand and the more recent approach based on the shortage function on the other hand. Moreover, we explain the working of these different methodologies in detail and provide graphical illustrations. Inspired by these illustrations, we prove a generalization of the well-known two fund separation theorem from traditionalmean-variance portfolio theory.

Two complementary molecular energy decomposition schemes: the Mayer and Ziegler-Rauk methods in comparison

In the present paper we discuss and compare two different energy decomposition schemes: Mayer's Hartree-Fock energy decomposition into diatomic and monoatomic contributions [Chem. Phys. Lett. 382, 265 (2003)], and the Ziegler-Rauk dissociation energy decomposition [Inorg. Chem. 18, 1558 (1979)]. The Ziegler-Rauk scheme is based on a separation of a molecule into fragments, while Mayer's scheme can be used in the cases where a fragmentation of the system in clearly separable parts is not possible. In the Mayer scheme, the density of a free atom is deformed to give the one-atom Mulliken density that subsequently interacts to give rise to the diatomic interaction energy. We give a detailed analysis of the diatomic energy contributions in the Mayer scheme and a close look onto the one-atom Mulliken densities. The Mulliken density ρA has a single large maximum around the nuclear position of the atom A, but exhibits slightly negative values in the vicinity of neighboring atoms. The main connecting point between both analysis schemes is the electrostatic energy. Both decomposition schemes utilize the same electrostatic energy expression, but differ in how fragment densities are defined. In the Mayer scheme, the electrostatic component originates from the interaction of the Mulliken densities, while in the Ziegler-Rauk scheme, the undisturbed fragment densities interact. The values of the electrostatic energy resulting from the two schemes differ significantly but typically have the same order of magnitude. Both methods are useful and complementary since Mayer's decomposition focuses on the energy of the finally formed molecule, whereas the Ziegler-Rauk scheme describes the bond formation starting from undeformed fragment densities

Topological comparison of methods for predicting transcriptional cooperativity in yeast

Background: The cooperative interaction between transcription factors has a decisive role in the control of the fate of the eukaryotic cell. Computational approaches for characterizing cooperative transcription factors in yeast, however, are based on different rationales and provide a low overlap between their results. Because the wealth of information contained in protein interaction networks and regulatory networks has proven highly effective in elucidating functional relationships between proteins, we compared different sets of cooperative transcription factor pairs (predicted by four different computational methods) within the frame of those networks. Results: Our results show that the overlap between the sets of cooperative transcription factors predicted by the different methods is low yet significant. Cooperative transcription factors predicted by all methods are closer and more clustered in the protein interaction network than expected by chance. On the other hand, members of a cooperative transcription factor pair neither seemed to regulate each other nor shared similar regulatory inputs, although they do regulate similar groups of target genes. Conclusion: Despite the different definitions of transcriptional cooperativity and the different computational approaches used to characterize cooperativity between transcription factors, the analysis of their roles in the framework of the protein interaction network and the regulatory network indicates a common denominator for the predictions under study. The knowledge of the shared topological properties of cooperative transcription factor pairs in both networks can be useful not only for designing better prediction methods but also for better understanding the complexities of transcriptional control in eukaryotes.

A limited area model intercomparison on the "Montserrat-2000" flash-flood event using statistical and deterministic methods

In the scope of the European project Hydroptimet, INTERREG IIIB-MEDOCC programme, limited area model (LAM) intercomparison of intense events that produced many damages to people and territory is performed. As the comparison is limited to single case studies, the work is not meant to provide a measure of the different models' skill, but to identify the key model factors useful to give a good forecast on such a kind of meteorological phenomena. This work focuses on the Spanish flash-flood event, also known as "Montserrat-2000" event. The study is performed using forecast data from seven operational LAMs, placed at partners' disposal via the Hydroptimet ftp site, and observed data from Catalonia rain gauge network. To improve the event analysis, satellite rainfall estimates have been also considered. For statistical evaluation of quantitative precipitation forecasts (QPFs), several non-parametric skill scores based on contingency tables have been used. Furthermore, for each model run it has been possible to identify Catalonia regions affected by misses and false alarms using contingency table elements. Moreover, the standard "eyeball" analysis of forecast and observed precipitation fields has been supported by the use of a state-of-the-art diagnostic method, the contiguous rain area (CRA) analysis. This method allows to quantify the spatial shift forecast error and to identify the error sources that affected each model forecasts. High-resolution modelling and domain size seem to have a key role for providing a skillful forecast. Further work is needed to support this statement, including verification using a wider observational data set.

A comparison of three established age estimation methods on an adult Spanish sample.

Most current methods for adult skeletal age-at-death estimation are based on American samples comprising individuals of European and African ancestry. Our limited understanding of population variability hampers our efforts to apply these techniques to various skeletal populations around the world, especially in global forensic contexts. Further, documented skeletal samples are rare, limiting our ability to test our techniques. The objective of this paper is to test three pelvic macroscopic methods (1-Suchey-Brooks; 2- Lovejoy; 3- Buckberry and Chamberlain) on a documented modern Spanish sample. These methods were selected because they are popular among Spanish anthropologists and because they never have been tested in a Spanish sample. The study sample consists of 80 individuals (55 ♂ and 25 ♀) of known sex and age from the Valladolid collection. Results indicate that in all three methods, levels of bias and inaccuracy increase with age. The Lovejoy method performs poorly (27%) compared with Suchey-Brooks (71%) and Buckberry and Chamberlain (86%). However, the levels of correlation between phases and chronological ages are low and comparable in the three methods (< 0.395). The apparent accuracy of the Suchey-Brooks and Buckberry and Chamberlain methods is largely based on the broad width of the methods" estimated intervals. This study suggests that before systematic application of these three methodologies in Spanish populations, further statistical modeling and research into the co-variance of chronological age with morphological change is necessary. Future methods should be developed specific to various world populations, and should allow for both precision and flexibility in age estimation.

Determining shoal membership: A comparison between momentary and trajectory-based methods

Miller and Gerlai proposed two methods for determining shoal membership in Danio rerio, one based on momentary mean inter-individual distances and the other on post hoc analysis of the trajectories of nearest-neighbor distances. We propose a method based on momentary nearest-neighbor distances and compare the three methods using simulation. In general, our method yielded results that were more similar to their second method than their first one, and is computationally simpler.

Comparison of three analytical methods for the determination of quinolones in pig muscle samples

This work presents a comparison between three analytical methods developed for the simultaneous determination of eight quinolones regulated by the European Union (marbofloxacin, ciprofloxacin, danofloxacin, enrofloxacin, difloxacin, sarafloxacin, oxolinic acid and flumequine) in pig muscle, using liquid chromatography with fluorescence detection (LC-FD), liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The procedures involve an extraction of the quinolones from the tissues, a step for clean-up and preconcentration of the analytes by solid-phase extraction and a subsequent liquid chromatographic analysis. The limits of detection of the methods ranged from 0.1 to 2.1 ng g−1 using LC-FD, from 0.3 to 1.8 using LC-MS and from 0.2 to 0.3 using LC-MS/MS, while inter- and intra-day variability was under 15 % in all cases. Most of those data are notably lower than the maximum residue limits established by the European Union for quinolones in pig tissues. The methods have been applied for the determination of quinolones in six different commercial pig muscle samples purchased in different supermarkets located in the city of Granada (south-east Spain).

Catalase in fluvial biofilms: a comparison between different extraction methods and example of application in a metal-polluted river

Antioxidant enzymes are involved in important processes of cell detoxification during oxidative stress and have, therefore, been used as biomarkers in algae. Nevertheless, their limited use in fluvial biofilms may be due to the complexity of such communities. Here, a comparison between different extraction methods was performed to obtain a reliable method for catalase extraction from fluvial biofilms. Homogenization followed by glass bead disruption appeared to be the best compromise for catalase extraction. This method was then applied to a field study in a metal-polluted stream (Riou Mort, France). The most polluted sites were characterized by a catalase activity 4–6 times lower than in the low-polluted site. Results of the comparison process and its application are promising for the use of catalase activity as an early warning biomarker of toxicity using biofilms in the laboratory and in the field