Investigation of pharmaceutical metabolites in environmental waters by LC-MS/MS

Pharmaceuticals, once ingested, are commonly metabolized in the body into more polar and soluble forms. These compounds might not be completely removed in the wastewater treatment plants and consequently being discharged into the aquatic ecosystem. In this work, a multi-class sensitive method for the analysis of 21 compounds, including 7 widely consumed pharmaceuticals and 14 relevant metabolites, has been developed based on the use of UHPLC-MS/MS in selected reaction monitoring (SRM) mode. The method was validated in six surface waters (SW) and six effluent wastewaters (EWW) at realistic concentration levels that can be found in waters. The optimized method was applied to the analysis of different types of water samples (rivers, lakes and effluent wastewater), detecting nearly all the parent compounds and metabolites investigated in this work. This fact illustrates that not only pharmaceuticals but also their metabolites are commonly present in these types of waters. Analytical research and monitoring programs should be directed not only towards parent pharmaceuticals but also towards relevant metabolites to have a realistic overview of the impact of pharmaceuticals in the aquatic environment

Tangential-flow membrane clarification of Malvar (Vitis vinifera L.) wine: incidence on chemical composition and sensorial expression

Malvar white wine (Vilis vinifera L.) was cold settled (CSW) and clarified by tangential-flow membrane filtration (TFMF). A 500 kDa molecular mass cut-off membrane was used. Filtration flux of 49-48 L/hm(2) was achieved at transmembrane pressure of 0.7 bar. The treatment produced a completely clarified wine with turbidity of 0.11 NTU, but also a 10.3 % loss of proteins, which could be related to the decrease of some flavour compounds. The CSW and the membrane filtered wines (MFW) were assessed by means of their aroma and phenolic composition, as well as their sensory properties. The results showed that the general physicochemical parameters and most of the analysed phenolic compounds were not or slightly (up to 7.6 %) affected by the TFMF process. Nevertheless, the treatment produced an important loss of some key aroma compounds: up to 43 % of fatty acid and alcohol esters and up to 26 % of higher alcohols. Most affected were aroma species with higher molecular masses and lower polarities. Sensory analysis confirmed the global decrease in wine aroma. TFMF treatment produced also an increase of 52 % of the wine benzaldehyde content

A "Politically Robust" Experimental Design for Public Policy Evaluation, with Application to the Mexican Universal Health Insurance Program

We develop an approach to conducting large scale randomized public policy experiments intended to be more robust to the political interventions that have ruined some or all parts of many similar previous efforts. Our proposed design is insulated from selection bias in some circumstances even if we lose observations; our inferences can still be unbiased even if politics disrupts any two of the three steps in our analytical procedures; and other empirical checks are available to validate the overall design. We illustrate with a design and empirical validation of an evaluation of the Mexican Seguro Popular de Salud (Universal Health Insurance) program we are conducting. Seguro Popular, which is intended to grow to provide medical care, drugs, preventative services, and financial health protection to the 50 million Mexicans without health insurance, is one of the largest health reforms of any country in the last two decades. The evaluation is also large scale, constituting one of the largest policy experiments to date and what may be the largest randomized health policy experiment ever.Governmen

Expression Profiles and DNA-Binding Affinity of Five ERF Genes in Bunches of Vitis vinifera cv. Cardinal Treated with High Levels of CO2 at Low Temperature

Ethylene response factors (ERFs) play an important role in plants by regulating defense response through interaction with various stress pathways. After harvest, table grapes (Vitis vinifera L.) are subject to a range of problems associated with postharvest storage at 0°C, such as fungal attack, water loss and rachis browning. The application of a 3-day high CO2 treatment maintained fruit quality and activated the induction of transcription factors belonging to different families such as ERF. In this paper, we have isolated five VviERFs from table grapes cv. Cardinal, whose deduced amino acid sequence contained the conserved apetalous (AP2)/ERF domain. The phylogeny and putative conserved motifs in VviERFs were analyzed and compared with those previously reported in Vitis. VviERFs-c gene expression was studied by quantitative real-time RT-PCR in the different tissues of bunches stored at low temperature and treated with high levels of CO2. The results showed that in most of the tissues analyzed, VviERFs-c gene expression was induced by the storage under normal atmosphere although the application of high levels of CO2 caused a greater increase in the VviERFs-c transcript accumulation. The promoter regions of two PRs (pathogenesis related proteins), Vcchit1b and Vcgns1, were obtained and the in silico analysis revealed the presence of a cis-acting ethylene response element (GCC box). In addition, expression of these two PR genes was analyzed in the pulp and rachis of CO2-treated and non-treated table grapes stored at 0°C and results showed significant correlations with VviERF2-c and VviERF6L7-c gene expression in rachis, and between VviERF11-c and Vcchit1b in pulp. Finally by using electro mobility shift assays, we denoted differences in binding of VviERFs to the GCC sequences present in the promoters of both PRs, with VviERF6L7-c being the only member which did not bind to any tested probe. Overall, our results suggest that the beneficial effect of high CO2 treatment maintaining table grape quality seems to be mediated by the regulation of ERFs and in particular VviERF2-c might play an important role by modulating the expression of PR genes.This work was supported by the European Union under the 7th Framework Programme FP7-PEOPLE-2012-CIG no. 321694 and by CICYT projects AGL2011-26742 and AGL2014-53081-R. IR and MV-H were supported by a postdoctoral Juan de la Cierva contract from the MICINN and a predoctoral contract from the MEC, respectively.USD 2,116.5 APC fee funded by the EC FP7 Post-Grant Open Access PilotPeer reviewe

Experimental validation for chatter stability prediction

This research focused on the experimental validation for chatter stability prediction. An optimum machining was aimed to maximize the material removal rate, whilst maintaining a sufficient stability margin to assure the surface quality. High material removal rate in machining produced self-excited vibration or chatter of the cutting tool and the workpiece. This resulted in a poor surface finish and dimensional accuracy, chipping of the cutter teeth, and also may damage the workpiece as well as machining tool. Frequency response function of a single degree freedom flexural was measured and the cutting stiffness of tools were determined in order to be used in predicting chatter stability using semi discretization method. The aluminium 7075 specimens were used in the milling cutting experiment to validate the chatter stability diagram of mill uniform and variable cutters, where a set of spindle speed and depth of cut had tested. The vibration conditions of machining were identified by analysing the vibration signals and FFT spectrum whether it was stable or in a chatter condition. There are good agreement between predicted stability and cutting experiment for the down-milling operation using uniform 4 flute cutting tool. Stable conditions were shown outside the boundary of chatter region. The optimized cutting tool was predicted to suppress chatter. Machining experiment tests showed there were no chatter vibration conditions during machining process until 1.5 mm depth of cut. According to the results of machining experiment, it was proven that the variable tool had more capability to machining without producing chatter vibration as compared to the regular tool

Identification of new omeprazole metabolites in wastewaters and surface waters

Omeprazole is one of the world-wide most consumed pharmaceuticals for treatment of gastric diseases. As opposed to other frequently used pharmaceuticals, omeprazole is scarcely detected in urban wastewaters and environmental waters. This was corroborated in a previous research, where parent omeprazole was not detected while four transformation products (TPs), mainly resulting from hydrolysis, were found in effluent wastewaters and surface waters. However, the low abundance of omeprazole TPs in the water samples together with the fact that omeprazole suffers an extensive metabolism, with a wide range of excretion rates (between 0.01 and 30%), suggests that human urinary metabolites should be investigated in the water environment. In this work, the results obtained in excretion tests after administration of a 40 mg omeprazole dose in three healthy volunteers are reported. Analysis by liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF MS) reported low concentrations of omeprazole in urine. Up to twenty-four omeprazole metabolites (OMs) were detected and tentatively elucidated. The most relevant OM was an omeprazole isomer, which obviously presented the same exact mass (m/z 346.1225), but also shared a major common fragment at m/z 198.0589. Subsequent analyses of surface water and effluent wastewater samples by both LC-QTOF MS and LC-MS/MS with triple quadrupole revealed that this metabolite (named as OM10) was the compound most frequently detected in water samples, followed by OM14a and OM14b. Up to our knowledge, OM10 had not been used before as urinary biomarker of omeprazole in waters. On the contrary, parent omeprazole was never detected in any of the water samples. After this research, it seems clear that monitoring the presence of omeprazole in the aquatic environment should be focused on the OMs suggested in this article instead of the parent compound

Boyeria Irene (Fonscolombe, 1838) y Cordulegaster Boltonii (Donovan, 1807) (Odonata): Dos estrategias en cuanto a sustratos de emergencia de larvas en un mismo hábitat.

Se presentan datos sobre emergencia de Cordulegaster boltonii y Boyeria irene en un río de montaña del centro de España (altitud 1200 m s.n.m.) donde coexisten ambas especies, basados en la recogida semanal de exuvias. Boyeria irene comenzó a emerger 28 días más tarde que C. boltonii. Los sustratos usados por las larvas de ambas especies para emerger se solaparon ampliamente, aunque C. boltonii utilizó significativamente más árboles. Con respecto a otras zonas geográficas, las dos especies han modificado su estrategia, retrasando el inicio del periodo de emergencia. Se discute la importancia de las condiciones ambientales (sobre todo temperatura) en este hecho

Mapping of mechanical properties of cement paste microstructures

The presented study is related to the EU 7 th Framework Programme CODICE (COmputationally Driven design of Innovative CEment-based materials). The main aim of the project is the development of a multi-scale model for the computer based simulation of mechanical and durability performance of cementitious materials. This paper reports results of micro/nano scale characterisation and mechanical property mapping of cementitious skeletons formed by the cement hydration at different ages. Using the statistical nanoindentation and micro-mechanical property mapping technique, intrinsic properties of different hydrate phases, and also the possible interaction (or overlapping) of different phases (e.g. calcium-silcate-hydrates) has been studied. Results of the mapping and statistical indentation testing appear to suggest the possible existence of more hydrate phases than the commonly reported LD and HD C-S-H and CH phase

Hydration of C3S, C2S and their Blends. Micro- and Nanoscale Characterization

This study forms part of wider research conducted under a EU 7 th Framework Programme (COmputationally Driven design of Innovative CEment-based materials or CODICE). The ultimate aim is the multi-scale modelling of the variations in mechanical performance in degraded and non-degraded cementitious matrices. The model is being experimentally validated by hydrating the main tri-calcium silicate (T1-C3S) and bi-calcium silicate (β-C2S), phases present in Portland cement and their blends. The present paper discusses micro- and nanoscale studies of the cementitious skeletons forming during the hydration of C3S, C2S and 70 % / 30 % blends of both C3S/C2S and C2S/C3S with a water/cement ratio of 0.4. The hydrated pastes were characterized at different curing ages with 29 Si NMR, SEM/TEM/EDS, BET, and nanoindentation. The findings served as a basis for the micro- and nanoscale characterization of the hydration products formed, especially C-S-H gels. Differences were identified in composition, structure and mechanical behaviour (nanoindentation), depending on whether the gels formed in C3S or C2S pastes. The C3S gels had more compact morphologies, smaller BET-N2 specific surface area and lesser porosity than the gels from C2S-rich pastes. The results of nanoindentation tests appear to indicate that the various C-S-H phases formed in hydrated C3S and C2S have the same mechanical properties as those formed in Portland cement paste. Compared to the C3S sample, the hydrated C2S specimen was dominated by the loose-packed (LP) and the low-density (LD) C-S-H phases, and had a much lower content of the high density (HD) C-S-H phas