Finite mixture clustering of human tissues with different levels of IGF-1 splice variants mRNA transcripts

BACKGROUND: This study addresses a recurrent biological problem, that is to define a formal clustering structure for a set of tissues on the basis of the relative abundance of multiple alternatively spliced isoforms mRNAs generated by the same gene. To this aim, we have used a model-based clustering approach, based on a finite mixture of multivariate Gaussian densities. However, given we had more technical replicates from the same tissue for each quantitative measurement, we also employed a finite mixture of linear mixed models, with tissue-specific random effects. RESULTS: A panel of human tissues was analysed through quantitative real-time PCR methods, to quantify the relative amount of mRNA encoding different IGF-1 alternative splicing variants. After an appropriate, preliminary, equalization of the quantitative data, we provided an estimate of the distribution of the observed concentrations for the different IGF-1 mRNA splice variants in the cohort of tissues by employing suitable kernel density estimators. We observed that the analysed IGF-1 mRNA splice variants were characterized by multimodal distributions, which could be interpreted as describing the presence of several sub-population, i.e. potential tissue clusters. In this context, a formal clustering approach based on a finite mixture model (FMM) with Gaussian components is proposed. Due to the presence of potential dependence between the technical replicates (originated by repeated quantitative measurements of the same mRNA splice isoform in the same tissue) we have also employed the finite mixture of linear mixed models (FMLMM), which allowed to take into account this kind of within-tissue dependence. CONCLUSIONS: The FMM and the FMLMM provided a convenient yet formal setting for a model-based clustering of the human tissues in sub-populations, characterized by homogeneous values of concentrations of the mRNAs for one or multiple IGF-1 alternative splicing isoforms. The proposed approaches can be applied to any cohort of tissues expressing several alternatively spliced mRNAs generated by the same gene, and can overcome the limitations of clustering methods based on simple comparisons between splice isoform expression levels

An integrated approach to prevent and treat respiratory failure in brain-injured patients

PURPOSE OF REVIEW: Brain-injured patients are at increased risk of extracerebral organ dysfunction, in particular ventilator-associated pneumonia. The purpose of this review is to discuss functional abnormalities, clinical treatment, and possible prevention of respiratory function abnormalities in brain-injured patients. RECENT FINDINGS: Ventilator-associated pneumonia worsens the neurologic outcome and increases the intensive care unit and hospital stay, costs, and risk of death. The respiratory dysfunction can be due to several causes, but atelectasis and/or consolidation of the lower lobes predominates in the most severe cases. Strategies should be implemented to prevent lung infections and accelerate weaning from mechanical ventilation to reduce the incidence of respiratory dysfunction and ventilator-associated pneumonia. SUMMARY: An integrated approach including appropriate ventilatory, antibiotic, and fluid management could be extremely useful, not only to prevent and more rapidly treat respiratory failure but also to improve neurologic outcome and reduce hospital stay. Further studies are warranted to better elucidate the pathophysiology and clinical treatment of respiratory dysfunction in brain-injured patients

Isogeometric Analysis in advection-diffusion problems: tension splines approximation

We present a novel approach, within the new paradigm of isogeometric analysis introduced by Hughes et al., to deal with advection dominated advection-diffusion problems. The key ingredient is the use of Galerkin approximating spaces of functions with high smoothness, as in IgA based on classical B-splines, but particularly well suited to describe sharp layers involving very strong gradients

Effects of organic pesticides on enchytraeids (Oligochaeta) in agroecosystems: laboratory and higher-tier tests

Enchytraeidae (Oligochaeta, Annelida) are often considered to be typical forestliving organisms, but they are regularly found in agroecosystems of the temperate regions of the world. Although less known than their larger relatives, the earthworms, these saprophagous organisms play similar roles in agricultural soils (but at a smaller scale), e.g., influencing soil structure and organic matter dynamics via microbial communities, and having a central place in soil food webs. Their diversity is rarely studied or often underestimated due to difficulties in distinguishing the species. New genetic techniques reveal that even in anthropogenically highly influenced soils, more than 10 species per site can be found. Because of their close contact with the soil pore water, a high ingestion rate and a thin cuticle, they often react very sensitively to a broad range of pesticides. Firstly we provide a short overview of the diversity and abundance of enchytraeid communities in agroecosystems. Afterwards, we explore the available data on enchytraeid sensitivity toward pesticides at different levels of biological organization, focusing on pesticides used in (mainly) European agroecosystems. Starting with non-standardized studies on the effects of pesticides on the sub-individual level, we compile the results of standard laboratory tests performed following OECD and ISO guidelines as well as those of higher-tier studies (i.e., semi-field and field tests). The number of comparable test data is still limited, because tests with enchytraeids are not a regulatory requirement in the European Union. While focusing on the effects of pesticides, attention is also given to their interactions with environmental stressors (e.g., climate change). In conclusion, we recommend to increase the use of enchytraeids in pesticide risk assessment because of their diversity and functional importance as well as their increasingly simplified use in (mostly standardized) tests at all levels of biological organization

Construction of planar quintic Pythagorean-hodograph curves by control-polygon constraints

In the construction and analysis of a planar Pythagorean–hodograph (PH) quintic curve r(t), t∈[0,1] using the complex representation, it is convenient to invoke a translation/rotation/scaling transformation so r(t) is in canonical form with r(0)=0, r(1)=1 and possesses just two complex degrees of freedom. By choosing two of the five control–polygon legs of a quintic PH curve as these free complex parameters, the remaining three control–polygon legs can be expressed in terms of them and the roots of a quadratic or quartic equation. Consequently, depending on the chosen two control–polygon legs, there exist either two or four distinct quintic PH curves that are consistent with them. A comprehensive analysis of all possible pairs of chosen control polygon legs is developed, and examples are provided to illustrate this control–polygon paradigm for the construction of planar quintic PH curves

Status of Salerno Laboratory (Measurements in Nuclear Emulsion)

A report on the analysis work in the Salerno Emulsion Laboratory is presented. It is related to the search for nu_mu->nu_tau oscillations in CHORUS experiment, the calibrations in the WANF (West Area Neutrino Facility) at Cern and tests and preparation for new experiments.Comment: Proc. The First International Workshop of Nuclear Emulsion Techniques (12-24 June 1998, Nagoya, Japan), 15 pages, 11 figure

Post-Traumatic Outcomes among Survivors of the Earthquake in Central Italy of August 24, 2016. A Study on PTSD Risk and Vulnerability Factors

Central Italy suffered from the earthquake of 2016 resulting in great damage to the community. The purpose of the present study was to determine the long-term traumatic outcomes among the population. A preliminary study aimed at obtaining the Italian translation of the first 16 item of HTQ IV part [1] which was administered, 20 months after the disaster, at 281 survivors. In backward stepwise logistic regressions models, we estimated among the respondent’s characteristics and event-related variables the best predictors of Post-Traumatic Stress Disorder (PTSD). A Confirmatory Factor Analysis (CFA) revealed a HTQ five-factors solution as best model, with satisfactory indexes of fit. HTQ held a positive correlation with both the SQD-P (r =.65, p <.05) and SQD-D subscales (r =.47, p <.05). ROC analysis suggested an area of.951 (95% CI =.917–.985) for the PTSD prediction. Basing on sensibility (.963) and specificity (.189), the best cut-off of 2.0 allowed discriminating for PTSD positive cases. After 20 months of the earthquake, the estimate prevalence of PTSD among the survivors is of 21.71% with a consistent and graded association between exposure variables and vulnerability factors (gender, age, exposure to death and home damage) and PTSD symptoms