Epidemiological and clinical data of hospitalizations associated with respiratory syncytial virus infection in children under 5 years of age in Spain: FIVE multicenter study.

BACKGROUND Respiratory syncytial virus (RSV) is an important pathogen in lower respiratory tract infections (LRTI) in infants, but there are limited data concerning patients with underlying conditions and children older than 2 years of age. METHODS We have designed a prospective observational multicenter national study performed in 26 Spanish hospitals (December 2011-March 2012). Investigational cases were defined as children with underlying chronic diseases and were compared with a group of previously healthy children (proportion 1:2). Clinical data were compared between the groups. RESULTS A total of 1763 children hospitalized due to RSV infection during the inclusion period were analyzed. Of them, 225 cases and 460 healthy children were enrolled in the study. Underlying diseases observed were respiratory (64%), cardiovascular (25%), and neurologic (12%), as well as chromosomal abnormalities (7·5%), immunodeficiencies (6·7%), and inborn errors of metabolism (3·5%). Cases were statistically older than previously healthy children (average age: 16·3 versus 5·5 months). Cases experienced hypoxemia more frequently (P < 0·001), but patients with respiratory diseases required oxygen therapy more often (OR: 2·99; 95% CI: 1·03-8·65). Mechanical ventilation was used more in patients with cardiac diseases (OR: 3·0; 95% CI: 1·07-8·44) and in those with inborn errors of metabolism (OR: 12·27; 95% CI: 2·11-71·47). This subgroup showed a higher risk of admission to the PICU (OR: 6·7, 95% CI: 1·18-38·04). Diagnosis of pneumonia was more frequently found in cases (18·2% versus 9·3%; P < 0·01). CONCLUSIONS A significant percentage of children with RSV infection have underlying diseases and the illness severity is higher than in healthy children.

Truncated robust distance for clinical laboratory safety data monitoring and assessment.

Laboratory safety data are routinely collected in clinical studies for safety monitoring and assessment. We have developed a truncated robust multivariate outlier detection method for identifying subjects with clinically relevant abnormal laboratory measurements. The proposed method can be applied to historical clinical data to establish a multivariate decision boundary that can then be used for future clinical trial laboratory safety data monitoring and assessment. Simulations demonstrate that the proposed method has the ability to detect relevant outliers while automatically excluding irrelevant outliers. Two examples from actual clinical studies are used to illustrate the use of this method for identifying clinically relevant outliers.

Comparative analysis of human and mouse expression data illuminates tissue-specific evolutionary patterns of miRNAs.

MicroRNAs (miRNAs) constitute an important class of gene regulators. While models have been proposed to explain their appearance and expansion, the validation of these models has been difficult due to the lack of comparative studies. Here, we analyze miRNA evolutionary patterns in two mammals, human and mouse, in relation to the age of miRNA families. In this comparative framework, we confirm some predictions of previously advanced models of miRNA evolution, e.g. that miRNAs arise more frequently de novo than by duplication, or that the number of protein-coding gene targeted by miRNAs decreases with evolutionary time. We also corroborate that miRNAs display an increase in expression level with evolutionary time, however we show that this relation is largely tissue-dependent, and especially low in embryonic or nervous tissues. We identify a bias of tag-sequencing techniques regarding the assessment of breadth of expression, leading us, contrary to predictions, to find more tissue-specific expression of older miRNAs. Together, our results refine the models used so far to depict the evolution of miRNA genes. They underline the role of tissue-specific selective forces on the evolution of miRNAs, as well as the potential co-evolution patterns between miRNAs and the protein-coding genes they target.

Hyperhidrosis: a new and often early symptom in Fabry disease. International experience and data from the Fabry Outcome Survey.

Hypohidrosis is a classic feature of Fabry disease; in contrast, hyperhidrosis has only been rarely described. The aim of the study is to characterise the baseline descriptive data on hyperhidrosis (frequency, age at onset, sex ratio and outcome with and without enzyme replacement therapy) in hemizygous male and heterozygous female patients with Fabry disease. We describe case histories of five patients with Fabry disease and hyperhidrosis seen at three different centres. We have also analysed a cohort of 21 paediatric patients in the UK and a large European cohort of patients enrolled in the Fabry Outcome Survey (FOS). Five patients (three female, two male) with hyperhidrosis were originally identified, although each had additional symptoms related to Fabry disease. The age at onset of hyperhidrosis was less than 18 years in four cases. In the cohort of 21 paediatric patients (12 female, nine male), one female had hyperhidrosis; the age at onset of this symptom was 11 years. In the FOS cohort, 66 of 714 patients with Fabry disease had hyperhidrosis (44 of 369 females, 11.9%; 22 of 345 males, 6.4%). The female predominance was observed in seven of nine countries from which data were analysed. Hyperhidrosis is an increasingly recognised feature of the Fabry disease phenotype. It is more prevalent in females than in males and often appears in childhood or adolescence. The efficacy of enzyme replacement therapy on this recently recognised symptom should be assessed.

Waterborne toxoplasmosis investigated and analysed under hydrogeological assessment: new data and perspectives for further research

We present a set of data on human and chicken Toxoplasma gondiiseroprevalence that was investigated and analysed in light of groundwater vulnerability information in an area endemic for waterborne toxoplasmosis in Brazil. Hydrogeological assessment was undertaken to select sites for water collection from wells for T. gondii oocyst testing and for collecting blood from free-range chickens and humans for anti-T. gondiiserologic testing. Serologic testing of human specimens was done using conventional commercial tests and a sporozoite-specific embryogenesis-related protein (TgERP), which is able to differentiate whether infection resulted from tissue cysts or oocysts. Water specimens were negative for the presence of viable T. gondii oocysts. However, seroprevalence in free-range chickens was significantly associated with vulnerability of groundwater to surface contamination (p < 0.0001; odds ratio: 4.73, 95% confidence interval: 2.18-10.2). Surprisingly, a high prevalence of antibodies against TgERP was detected in human specimens, suggesting the possibility of a continuous contamination of drinking water with T. gondiioocysts in this endemic setting. These findings and the new proposed approach to investigate and analyse endemic toxoplasmosis in light of groundwater vulnerability information associated with prevalence in humans estimated by oocyst antigens recognition have implications for the potential role of hydrogeological assessment in researching waterborne toxoplasmosis at a global scale.

Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: preliminary data from year 9 of the follow-up.

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01-1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort.

CAC controlled services sharing a link with connectionless data services in an ATM network: a performance evaluation study

In the B-ISDN there is a provision for four classes of services, all of them supported by a single transport network (the ATM network). Three of these services, the connected oriented (CO) ones, permit connection access control (CAC) but the fourth, the connectionless oriented (CLO) one, does not. Therefore, when CLO service and CO services have to share the same ATM link, a conflict may arise. This is because a bandwidth allocation to obtain maximum statistical gain can damage the contracted ATM quality of service (QOS); and vice versa, in order to guarantee the contracted QOS, the statistical gain have to be sacrificed. The paper presents a performance evaluation study of the influence of the CLO service on a CO service (a circuit emulation service or a variable bit-rate service) when sharing the same link

Studies in stoichiometry with compositional data

Geochemical data that is derived from the whole or partial analysis of various geologic materialsrepresent a composition of mineralogies or solute species. Minerals are composed of structuredrelationships between cations and anions which, through atomic and molecular forces, keep the elementsbound in specific configurations. The chemical compositions of minerals have specific relationships thatare governed by these molecular controls. In the case of olivine, there is a well-defined relationshipbetween Mn-Fe-Mg with Si. Balances between the principal elements defining olivine composition andother significant constituents in the composition (Al, Ti) have been defined, resulting in a near-linearrelationship between the logarithmic relative proportion of Si versus (MgMnFe) and Mg versus (MnFe),which is typically described but poorly illustrated in the simplex.The present contribution corresponds to ongoing research, which attempts to relate stoichiometry andgeochemical data using compositional geometry. We describe here the approach by which stoichiometricrelationships based on mineralogical constraints can be accounted for in the space of simplicialcoordinates using olivines as an example. Further examples for other mineral types (plagioclases andmore complex minerals such as clays) are needed. Issues that remain to be dealt with include thereduction of a bulk chemical composition of a rock comprised of several minerals from which appropriatebalances can be used to describe the composition in a realistic mineralogical framework. The overallobjective of our research is to answer the question: In the cases where the mineralogy is unknown, arethere suitable proxies that can be substituted?Kew words: Aitchison geometry, balances, mineral composition, oxides