Micro- and macro-porosity of dry- and saturatedstate recycled aggregate concrete

Society is becoming aware of the environment and progressively using more recycled aggregates to produce recycled structural aggregate concrete. In addition, many researches have analysed the properties of hardened recycled aggregate concrete, but few of them have focused on the mixing method and the consequences that it has on the properties of concrete. In this research, recycled aggregate concrete using dry, with extra water supply, and saturated recycled aggregate has been prepared. The different mixing conditions induce differences the micro and macroporosity of concrete that have been evaluated by computerized axial tomography, scanning electron microscopy and a new developed methodology, based on digital image analysis, developed to analyse the distribution and size of macroporosity. The software has been implemented in Matlab© and is available to the readers of the journal for downloading and use. The results show that the dry and saturated recycled aggregate lead to very different concrete properties. On the one hand, the use of dry aggregate causes a local reduction of the w/c ratio, increasing heterogeneity and decreasing workability. On the other hand, the saturated aggregate incorporates extra water by adsorption that causes an increase in the water/cement ratio, thus increasing the porosity volume and size of the new mortar of the recycled aggregate concrete

Steel waste valorisation Steel Slag Waste Effect on Concrete Shrinkage

The concept of sustainability is becoming widespread every day in society, enterprises and institutions. Defining something as sustainable means that the relationship that it establishes with the environment does not represent an aggression or a threat to the latter neither when it is being utilized nor when it stops performing the function for which was designed. To make this happen we need a system in which the main priority is recycling. Everything mentioned above is related to what is called the “Circular Economy”. Concrete is one of the most widely used construction materials in the world. However, the production of portland cement, an essential constituent of concrete, leads to the release of significant amounts of CO22. The global production of concrete represents more than 5% of the anthropogenic emissions of carbon dioxide every year, mainly from the production of cement. The replacement of cement by fly ash and other industrial waste, such as steel slags, is a good example of how resource conservation can be improved and contamination can be reduced. On the other hand, future trends are predicted to increase demand for steel worldwide. Mainly due to the expected improvement in the living standards and demands of underdeveloped populations. The steelmaking process produces a by-product called slag ranging from 10 to 15% per tonne of steel, where reuse is still reduced and much of it is deposited in a landfill. This study presents laboratory test results on the total and autogenous shrinkage of medium strength concrete with partial replacement of cement by slags. Two different slags were tested, namely ladle furnaces slags (LFS) and ground granulated blast furnace slags (GGBFS). The results show the concrete shrinkage behavior when 25% of substitution are used. These data are important to predict future behavior and show that for the substitution dosages used there are no significant divergences for the shrinkage.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Circular RNA CpG island hypermethylation-associated silencing in human cancer

Noncoding RNAs (ncRNAs), such as microRNAs and long noncoding RNAs (lncRNAs), participate in cellular transformation. Work done in the last decade has also demonstrated that ncRNAs with growth-inhibitory functions can undergo promoter CpG island hypermethylation-associated silencing in tumorigenesis. Herein, we wondered whether circular RNAs (circRNAs), a type of RNA transcripts lacking 5′-3′ ends and forming closed loops that are gaining relevance in cancer biology, are also a target of epigenetic inactivation in tumors. To tackle this issue, we have used cancer cells genetically deficient for the DNA methyltransferase enzymes in conjuction with circRNA expression microarrays. We have found that the loss of DNA methylation provokes a release of circRNA silencing. In particular, we have identified that promoter CpG island hypermethylation of the genes TUSC3 (tumor suppressor candidate 3), POMT1 (protein O-mannosyltransferase 1), ATRNL1 (attractin-like 1) and SAMD4A (sterile alpha motif domain containing 4A) is linked to the transcriptional downregulation of both linear mRNA and the hosted circRNA. Although some circRNAs regulate the linear transcript, we did not observe changes in TUSC3 mRNA levels upon TUSC3 circ104557 overexpression. Interestingly, we found circRNA-mediated regulation of target miRNAs and an in vivo growth inhibitory effect upon TUSC3 circ104557 transduction. Data mining for 5′-end CpG island methylation of TUSC3, ATRNL1, POMT1 and SAMD4A in cancer cell lines and primary tumors showed that the epigenetic defect was commonly observed among different tumor types in association with the diminished expression of the corresponding transcript. Our findings support a role for circRNA DNA methylation-associated loss in human cancer

Pattern of long-Term weight and metabolic changes after a first-episode of psychosis: Results from a 10-years prospective follow-up of the PAFIP cohort

Background: People with psychosis are at higher risk of cardiovascular events, partly explained by a higher predisposition to gain weight. This has been observed in studies on individuals with a first-episode psychosis (FEP) at short and long term (mainly up to 1 year) and transversally at longer term in people with chronic schizophrenia. However, there is scarcity of data regarding longer-term (above 3-year follow-up) weight progression in FEP from longitudinal studies. The aim of this study is to evaluate the longer-term (10 years) progression of weight changes and related metabolic disturbances in people with FEP. Methods: Two hundred and nine people with FEP and 57 healthy participants (controls) were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric, clinical, and sociodemographic data were collected. Results: People with FEP presented a significant and rapid increase in mean body weight during the first year of treatment, followed by less pronounced but sustained weight gain over the study period (?15.2 kg; SD 12.3 kg). This early increment in weight predicted longer-term changes, which were significantly greater than in healthy controls (?2.9 kg; SD 7.3 kg). Weight gain correlated with alterations in lipid and glycemic variables, leading to clinical repercussion such as increments in the rates of obesity and metabolic disturbances. Sex differences were observed, with women presenting higher increments in body mass index than men. Conclusions: This study confirms that the first year after initiating antipsychotic treatment is the critical one for weight gain in psychosis. Besides, it provides evidence that weight gain keep progressing even in the longer term (10 years), causing relevant metabolic disturbances

Epigenetic silencing of TGFBI confers resistance to trastuzumab in human breast cancer

Background: acquired resistance to trastuzumab is a major clinical problem in the treatment of HER2-positive (HER2+) breast cancer patients. The selection of trastuzumab-resistant patients is a great challenge of precision oncology. The aim of this study was to identify novel epigenetic biomarkers associated to trastuzumab resistance in HER2+ BC patients. Methods: we performed a genome-wide DNA methylation (450K array) and a transcriptomic analysis (RNA-Seq) comparing trastuzumab-sensitive (SK) and trastuzumab-resistant (SKTR) HER2+ human breast cancer cell models. The methylation and expression levels of candidate genes were validated by bisulfite pyrosequencing and qRT-PCR, respectively. Functional assays were conducted in the SK and SKTR models by gene silencing and overexpression. Methylation analysis in 24 HER2+ human BC samples with complete response or non-response to trastuzumab-based treatment was conducted by bisulfite pyrosequencing. Results: epigenomic and transcriptomic analysis revealed the consistent hypermethylation and downregulation of TGFBI, CXCL2, and SLC38A1 genes in association with trastuzumab resistance. The DNA methylation and expression levels of these genes were validated in both sensitive and resistant models analyzed. Of the genes, TGFBI presented the highest hypermethylation-associated silencing both at the transcriptional and protein level. Ectopic expression of TGFBI in the SKTR model suggest an increased sensitivity to trastuzumab treatment. In primary tumors, TGFBI hypermethylation was significantly associated with trastuzumab resistance in HER2+ breast cancer patients. Conclusions: our results suggest for the first time an association between the epigenetic silencing of TGFBI by DNA methylation and trastuzumab resistance in HER2+ cell models. These results provide the basis for further clinical studies to validate the hypermethylation of TGFBI promoter as a biomarker of trastuzumab resistance in HER2+ breast cancer patients

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial

BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics

Fatigue limit of recycled aggregate concrete

This paper presents the main results of the research carried out to obtain the fatigue limit of concrete incorporating recycled aggregate from concrete. In this research, recycled aggregate concretes with partial and total coarse aggregate replacement and control concretes with different increasing water/cement ratios have been cast to study the material’s behavior in response to repeated compressive loads. The results show that, for the same water/cement ratio, the recycled aggregate concretes present a loss of stiffness higher than the control concrete. Furthermore, the use of recycled aggregate in concrete implies a reduction of the fatigue life. These differences are increased for low water/cement ratios, as in this case the main factor is the lower strength capacity of the aggregate. From the results obtained, recommendable mixtures for recycled aggregates exposed to fatigue loads are proposed

Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis

Germline mutations in BUB1 and BUB3 have been reported to increase the risk of developing colorectal cancer (CRC) at young age, in presence of variegated aneuploidy and reminiscent dysmorphic traits of mosaic variegated aneuploidy syndrome. We performed a mutational analysis of BUB1 and BUB3 in 456 uncharacterized mismatch repair-proficient hereditary non-polyposis CRC families and 88 polyposis cases. Four novel or rare germline variants, one splice-site and three missense, were identified in four families. Neither variegated aneuploidy nor dysmorphic traits were observed in carriers. Evident functional effects in the heterozygous form were observed for c.1965-1G>A, but not for c.2296G>A (p.E766K), in spite of the positive co-segregation in the family. BUB1 c.2473C>T (p.P825S) and BUB3 c.77C>T (p.T26I) remained as variants of uncertain significance. As of today, the rarity of functionally relevant mutations identified in familial and/or early onset series does not support the inclusion of BUB1 and BUB3 testing in routine genetic diagnostics of familial CRC

Complications of Peripherally Inserted Central Venous Catheters: A Retrospective Cohort Study

Background and Aim The use of venous catheters is a widespread practice, especially in oncological and oncohematological units. The objective of this study was to evaluate the complications associated with peripherally inserted central catheters (PICCs) in a cohort of patients. Materials and Methods In this retrospective cohort study, we included all patient carrying PICCs (n = 603) inserted at our institute between October 2010 and December 2013. The main variables collected were medical diagnosis, catheter care, location, duration of catheterization, reasons for catheter removal, complications, and nursing care. Complications were classified as infection, thrombosis, phlebitis, migration, edema, and/or ecchymosis. Results All patients were treated according to the same “nursing care” protocol. The incidence rate of complications was two cases per 1000 days of catheter duration. The most relevant complications were infection and thrombosis, both with an incidence of 0.17 cases per 1000 days of the total catheterization period. The total average duration of catheterization was 170 days [SD 6.06]. Additionally to “end of treatment” (48.42%) and “exitus”, (22.53%) the most frequent cause of removal was migration (displacement towards the exterior) of the catheter (5.80%). Conclusions PICCs are safe devices that allow the administration of long-term treatment and preserve the integrity of the venous system of the patient. Proper care of the catheter is very important to improve the quality life of patients with oncologic and hematologic conditions. Therefore, correct training of professionals and patients as well as following the latest scientific recommendations are particularly relevant