Developing speed-related safety performance indicators from floating car data

In the road traffic safety domain there is a need for using proactive (non-crash-based) indicators, known as safety performance indicators (SPIs). Traffic speed based on big data (floating car data [FCD]) could help develop network-wide SPIs, but related knowledge and experience are insufficient so far. The authors attempted to fill this gap by using nationwide Italian FCD to develop speed-related SPIs and validating their relationship to crashes to see their potential explanatory value. The authors calculated the coefficient of variance (CV), congestion index (CI), and the number of incidents as candidate SPIs. For validation, the authors used linear correlation, crash frequency model, and ranking consistency. Incidents turned out to be the best SPI, especially for motorways

Effect of life history on microRNA expression during C. elegans development

Animals have evolved mechanisms to ensure the robustness of developmental outcomes to changing environments. MicroRNA expression may contribute to developmental robustness because microRNAs are key post-transcriptional regulators of developmental gene expression and can affect the expression of multiple target genes. Caenorhabditis elegans provides an excellent model to study developmental responses to environmental conditions. In favorable environments, C. elegans larvae develop rapidly and continuously through four larval stages. In contrast, in unfavorable conditions, larval development may be interrupted at either of two diapause stages: The L1 diapause occurs when embryos hatch in the absence of food, and the dauer diapause occurs after the second larval stage in response to environmental stimuli encountered during the first two larval stages. Dauer larvae are stress resistant and long lived, permitting survival in harsh conditions. When environmental conditions improve, dauer larvae re-enter development, and progress through two post-dauer larval stages to adulthood. Strikingly, all of these life history options (whether continuous or interrupted) involve an identical pattern and sequence of cell division and cell fates. To identify microRNAs with potential functions in buffering development in the context of C. elegans life history options, we used multiplex real-time PCR to assess the expression of 107 microRNAs throughout development in both continuous and interrupted life histories. We identified 17 microRNAs whose developmental profile of expression is affected by dauer life history and/or L1 diapause, compared to continuous development. Hence these microRNAs could function to regulate gene expression programs appropriate for different life history options in the developing worm

Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression

microRNAs function in diverse developmental and physiological processes by regulating target gene expression at the post-transcriptional level. ALG-1 is one of two Caenorhabditis elegans Argonautes (ALG-1 and ALG-2) that together are essential for microRNA biogenesis and function. Here, we report the identification of novel antimorphic (anti) alleles of ALG-1 as suppressors of lin-28(lf) precocious developmental phenotypes. The alg-1(anti) mutations broadly impair the function of many microRNAs and cause dosage-dependent phenotypes that are more severe than the complete loss of ALG-1. ALG-1(anti) mutant proteins are competent for promoting Dicer cleavage of microRNA precursors and for associating with and stabilizing microRNAs. However, our results suggest that ALG-1(anti) proteins may sequester microRNAs in immature and functionally deficient microRNA Induced Silencing Complexes (miRISCs), and hence compete with ALG-2 for access to functional microRNAs. Immunoprecipitation experiments show that ALG-1(anti) proteins display an increased association with Dicer and a decreased association with AIN-1/GW182. These findings suggest that alg-1(anti) mutations impair the ability of ALG-1 miRISC to execute a transition from Dicer-associated microRNA processing to AIN-1/GW182 associated effector function, and indicate an active role for ALG/Argonaute in mediating this transition

How to minimise the effect of tumour cell content in detection of aberrant genetic markers in neuroblastoma

Background:Clinical heterogeneity reflects the complexity of genetic events associated with neuroblastoma (NB). To identify the status of all described genetic loci with possible prognostic interest, high-throughput approaches have been used, but only with tumour cell content >60%. In some tumours, necrotic, haemorrhagic and/or calcification areas influence the low amount of neuroblasts. We evaluated the effect of tumour cell content in the detection of relevant aberrant genetic markers (AGM) diagnosed by fluorescence in situ hybridisation (FISH) on tissue microarrays (TMA) in NB.Methods:Two hundred and thirty-three MYCN non-amplified primary NB included in 12 TMAs were analysed.Results:Presence of AGM reduced event-free survival (EFS) (P=0.004) as well as overall survival (OS) (P=0.004) of patients in the whole cohort. There were no differences in prognostic impact of presence of AGM according to tumour cell content.Conclusion:We propose the use of FISH to diagnose AGM of all NB samples having the above-mentioned areas to determine patient risk

Giant pulmonary bulla mimicking pneumothorax in children. Diagnostic and morphopathological considerations

Rezumat Introducere. Bula pulmonară gigantă la copii se întâlnește rar. În acest context, autorii prezintă un caz clinic, care demonstrează dificultățile diagnostice, modalitatea de tratament chirurgical și aspectele morfopatologice ale acestei entități nozologice. Prezentare de caz. Pacient de sex masculin, în vârstă de 12 ani, care prezenta astenie, slăbiciune la efort fizic și dispnee timp de 8 luni, a fost internat pentru pneumotorax spontan pe dreapta, diagnosticul fiind stabilit la radiografie toracică și confirmat la tomografie computerizată. Concomitent, pacientul suferea de timomegalie cu hipotiroidie primară congenitală, în legătură cu ce urmează tratament cu L-tiroxină, și formațiune chistică a glandei tiroide supusă tratamentului chirurgical. Pacientul a fost supus intervenției chirurgicale toracice video asistate (VATS), intraoperator fiind identificată o bulă gigantă localizată în lobul superior al plămânului drept, care a fost excizată prin micro toracotomie latero-posterioară dreaptă. Evoluția postoperatorie a fost fără particularități, radiologic fiind constatată expansiunea treptată a lobului superior al plămânului drept, în care scintigrafia pulmonară a pus în evidență modificări nesemnificative de perfuzie pulmonară. Concluzii. 1. Diagnosticul diferențial dintre bula pulmonară gigantică și pneumotorax este destul de dificil, fiind esențial în aprecierea tacticii de tratament. 2. Bulectomia cu suturarea și aerostaza adecvată a liniei de rezecție la nivelul țesutului pulmonar sănătos reprezintă un procedeu tehnic sigur și fezabil în rezolvarea acestei patologii. 3. Investigațiile histologice efectuate în acest caz au permis de a stabili unele particularități morfopatologice ale componentelor structurale, acestea fiind caracteristice pentru o formațiune chistică de origine bronșică, care conținea elemente de țesuturi musculare reziduale, fascicule nervoase, arterii obliterate sclerogenizate, precum și componenta limfocitară pseudo-foliculară, modificările constatate punând în discuție originea dizontogenetică a bulei pulmonare gigante la copii.Summary Introduction. Giant lung blistering in children is rare. In this context, the authors present a clinical case, which demonstrates the diagnostic difficulties, the way of surgical treatment and the morphopathological aspects of this nosological entity. Case report. A 12-year-old male patient with asthenia, weakness on exertion and dyspnea for 8 months was hospitalized for spontaneous right pneumothorax, the diagnosis being established by chest radiography and confirmed by computed tomography. At the same time, the patient was suffering from thymomegaly with congenital primary hypothyroidism, because of which gets treatment with L-thyroxin, and cystic formation of the thyroid gland undergoing surgical treatment. The patient underwent video-assisted thoracic surgery (VATS), and a giant bladder located in the upper lobe of the right lung was identified intraoperative, which was excised by right latero-posterior micro thoracotomy. The postoperative evolution was without particularities, radiologically being found the gradual re-expansion of the upper lobe of the right lung, in which the pulmonary scintigraphy revealed insignificant changes of pulmonary perfusion. Conclusions. 1. The differential diagnosis between giant lung blister and pneumothorax is quite difficult, being essential in assessing treatment tactics. 2. Bulectomy with suturing and adequate aerostasis of the resection line at the level of healthy lung tissue is a safe and feasible technical procedure in resolving this pathology. 3. The carried out histological investigations, in this case, established some morphopathological features of the structural components, which are characteristic of a cystic formation of bronchial origin, which contained elements of residual muscle tissue, nerve bundles, sclerogenized-obliterated arteries and lymphocyte component. Pseudo-follicular, the changes found questioning the dysontogenetic origin of the giant lung bubble in children

Development of land-use regression models for fine particles and black carbon in peri-urban South India

Land-use regression (LUR) has been used to model local spatial variability of particulate matter in cities of high-income countries. Performance of LUR models is unknown in less urbanized areas of low-/middle-income countries (LMICs) experiencing complex sources of ambient air pollution and which typically have limited land use data. To address these concerns, we developed LUR models using satellite imagery (e.g., vegetation, urbanicity) and manually-collected data from a comprehensive built-environment survey (e.g., roads, industries, non-residential places) for a peri-urban area outside Hyderabad, India. As part of the CHAI (Cardiovascular Health effects of Air pollution in Telangana, India) project, concentrations of fine particulate matter (PM2.5) and black carbon were measured over two seasons at 23 sites. Annual mean (sd) was 34.1 (3.2) mug/m(3) for PM2.5 and 2.7 (0.5) mug/m(3) for black carbon. The LUR model for annual black carbon explained 78% of total variance and included both local-scale (energy supply places) and regional-scale (roads) predictors. Explained variance was 58% for annual PM2.5 and the included predictors were only regional (urbanicity, vegetation). During leave-one-out cross-validation and cross-holdout validation, only the black carbon model showed consistent performance. The LUR model for black carbon explained a substantial proportion of the spatial variability that could not be captured by simpler interpolation technique (ordinary kriging). This is the first study to develop a LUR model for ambient concentrations of PM2.5 and black carbon in a non-urban area of LMICs, supporting the applicability of the LUR approach in such settings. Our results provide insights on the added value of manually-collected built-environment data to improve the performance of LUR models in settings with limited data availability. For both pollutants, LUR models predicted substantial within-village variability, an important feature for future epidemiological studies

Biodistribution and function of extracellular miRNA-155 in mice

Circulating miRNAs can be found in extracellular vesicles (EV) and could be involved in intercellular communication. Here, we report the biodistribution of EV associated miR-155 using miR-155 KO mouse model. Administration of exosomes loaded with synthetic miR-155 mimic into miR-155 KO mice resulted in a rapid accumulation and clearance of miR-155 in the plasma with subsequent distribution in the liver, adipose tissue, lung, muscle and kidney (highest to lowest, respectively). miR-155 expression was detected in isolated hepatocytes and liver mononuclear cells of recipient KO mice suggesting its cellular uptake. In vitro, exosome-mediated restoration of miR-155 in Kupffer cells from miR-155 deficient mice augmented their LPS-induced MCP1 mRNA increase. The systemic delivery of wild type plasma to miR-155 KO mice also resulted in a rapid accumulation of miR-155 in the circulation and distribution to the liver and adipose tissue. In summary, our results demonstrate tissue biodistribution and biologic function of EV-associated miR-155

Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project

Background: In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested. Methods: The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. Only tumours with a confirmed unaltered status for all three chromosome arms were considered as having no segmental chromosomal alterations. Results: Among the 8800 patients in the INRG database, a genomic type could be attributed for 505 patients without MNA: 397 cases had a segmental genomic type, whereas 108 cases had an absence of any segmental alteration. A segmental genomic type was more frequent in patients >18 months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion, 17q gain and a segmental genomic type were associated with a poorer event-free survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate analysis modelling EFS, the parameters age, stage and a segmental genomic type were retained in the model, whereas the individual genetic markers were not (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively). Conclusion: A segmental genomic profile, rather than the single genetic markers, adds prognostic information to the clinical markers age and stage in neuroblastoma patients without MNA, underlining the importance of pangenomic studies

Identification of microRNAs with regulatory potential using a matched microRNA-mRNA time-course data

Over the past decade, a class of small RNA molecules called microRNAs (miRNAs) has been shown to regulate gene expression at the post-transcription stage. While early work focused on the identification of miRNAs using a combination of experimental and computational techniques, subsequent studies have focused on identification of miRNA-target mRNA pairs as each miRNA can have hundreds of mRNA targets. The experimental validation of some miRNAs as oncogenic has provided further motivation for research in this area. In this article we propose an odds-ratio (OR) statistic for identification of regulatory miRNAs. It is based on integrative analysis of matched miRNA and mRNA time-course microarray data. The OR-statistic was used for (i) identification of miRNAs with regulatory potential, (ii) identification of miRNA-target mRNA pairs and (iii) identification of time lags between changes in miRNA expression and those of its target mRNAs. We applied the OR-statistic to a cancer data set and identified a small set of miRNAs that were negatively correlated to mRNAs. A literature survey revealed that some of the miRNAs that were predicted to be regulatory, were indeed oncogenic or tumor suppressors. Finally, some of the predicted miRNA targets have been shown to be experimentally valid