1,354,584 research outputs found
Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database
No full textBackground: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk
“Potential carbon efficiency” as a new index to track the performance of biofuels production processes
No full textIn a carbon constrained economy which targets a massive reduction of the CO2 emissions, biogenic carbon is bound to be a scarce resource with high economic value. In such scenario, the carbon efficiency may become the key performance index to represent the revenues of the biomass-to-X conversion plants. In this work, the potential carbon efficiency (PCE) indicator is defined to quantify the achievable carbon efficiency (i.e. the amount of carbon contained in the final product with respect to the available input carbon), of a stream or of a process unit. Compared to the conventional carbon efficiency (CE), that is affected only by the separation/addition of carbon-containing species, the PCE allows quantifying the potential variation of the achievable carbon efficiency in process units where no carbon separation occurs, but where a limiting element is added (e.g. hydrogen through steam addition) or oxygen content is increased (e.g. oxygen injection in a reformer). The difference between the CE and the PCE along a biomass conversion process is typically due to the excess of oxygen atoms in the syngas, which is removed as CO2 in the syngas conditioning unit. Therefore, the difference between CE and PCE shows the potential gain in carbon efficiency that can be obtained by the addition of H2 from an electrolysis process. In this paper, the PCE and the CE have been calculated along the process units of different biomass-to-X plants. The selected case studies allow comparing different gasification technologies (direct gasification, indirect gasification and sorption enhanced gasification) in plants for the production of methanol and synthetic natural gas, showing how CE and PCE are influenced by process units such as the gasification technology, syngas reforming, syngas conditioning and hydrogen addition
Flexible methanol and hydrogen production from biomass gasification with negative emissions
No full textBioenergy plants with carbon capture and storage have been recently receiving attention as negative emission technologies. In this work, a techno-economic analysis of bio-methanol and bio-hydrogen production plants coupled with carbon capture and storage is conducted. The plants include different gasification technologies (direct oxygen-blown gasification and indirect gasification) and different CO2 capture processes (pre-combustion MDEA-based and post-combustion MEA-based CO2 capture) from different streams, to achieve increasing CO2 capture rates at increasing marginal costs. Moreover, an assessment of the economic impact of multi-product plants which flexibly produce methanol and hydrogen is carried out. Overall fuel production efficiencies of between 65.1 and 68.1% have been computed in all cases, showing a little dependency of energy efficiency on the gasification technology and the final product. In methanol production plants, a CO2 capture rate of between 26 and 55%, depending on the gasification technology, can be reached via a pre-combustion capture process at a cost of 41-46 euro per tCO2. In hydrogen production plants, between 64 and 90% capture efficiency can be reached at a cost of 52-56 euro per tCO2. Higher CO2 capture efficiency, resulting in CO2 residual emissions below 2% of the inlet carbon, can be achieved via post-combustion capture with a marginal cost of 98-205 euro per tCO2 and an average cost of 47-77 euro per tCO2. Flexible methanol-H2 production plants result in the highest capex and the highest LCOF. However, when considering the time-dependent H2 market price, the internal rate of return of flexible methanol-H2 plants is slightly higher or slightly lower than that of the corresponding best single-product plant. On the other hand, multi-product flexible plants are never the worst case scenario despite the highest investment costs, thus offering a potential advantage from the financial risk perspective thanks to lower exposure to market price volatility
Metric Accuracy of Digital Elevation Models from WorldView-3 Stereo-Pairs in Urban Areas
No full textWorldView-3 satellite is providing images with an unprecedented combination of high spatial and spectral resolution. The stereo capabilities and the very high resolution of the panchromatic band (0.31 m) have been fostering new applications in urban areas, where the complexity of the morphology requires a higher level of detail. The present technical note aims to test the accuracy of digital elevation models that can be obtained by WorldView-3 stereo-pairs in these particular contexts, with an operational state-of-the-art algorithm. Validation is performed using check points and existing models of the area (from LiDAR data and oblique aerial images). The experiments, conducted over the city of Bologna (Italy) with six images, proved that roof surfaces and open spaces can be reconstructed with an average error of 1–2 pixels, but severe discrepancies frequently occur in narrow roads and urban canyons (up to several metres in average). The level of completeness achievable with only one pair is extremely variable (ranging from 50% to 90%), due to the combined effect of the geometry of acquisition and the specific urban texture. Better results can be obtained by using more than one pair. Furthermore, smaller convergence angles can be beneficial for the reconstruction of specific urban structures, such as soaring towers
Riduzione catalitica di ossido di azoto con etilene su catalizzatori a base di rame. Un’interpretazione cinetica
No full textToward a pharmacophore for drugs inducing the long QT syndrome: Insights from a CoMFA study of HERG K+ channel blockers
No full textIn this paper, we present a pharmacophore for QT-prolonging drugs, along with a 3D QSAR (CoMFA) study for a series of very structurally variegate HERG K+ channel blockers. The blockade of HERG K+ channels is one of the most important molecular mechanisms through which QT-prolonging drugs increase cardiac action potential duration. Since QT prolongation is one of the most undesirable side effects of drugs, we first tried to identify the minimum set of molecular features responsible for this action and then we attempted to develop a quantitative model correlating the 3D stereoelectronic characteristics of the molecules with their HERG blocking potency. Having considered an initial set of 31 QT-prolonging drugs for which the HERG K+ channel blocking activity was measured on mammalian transfected cells, we started the construction of a theoretical screening tool able to predict whether a new molecule can interact with the HERG channel and eventually induce the long QT syndrome. This in silico tool might be useful in the design of new drug candidates devoid of the physicochemical features likely to cause the above-mentioned side effect
The Potential of Power and Biomass-to-X Systems in the Decarbonization Challenge: a Critical Review
No full textPurpose of the Review: The scope of this work is to present a critical review of the novel class of plants for the enhanced production of bioproducts in power and biomass-to-X (PBtX) plants, where the excess carbon in the feedstock is converted into a product thanks to the addition of hydrogen from water electrolysis, rather than being vented as CO2. Recent Findings: The review of the recent literature shows that (i) a significant gain in carbon efficiency can be achieved with this class of plants compared to corresponding biomass-to-X plants; (ii) there is high dependency of the power-to-X efficiency on the efficiency of the electrolysis system and a relatively low dependency on the final product; and (iii) the economic competitivity of PBtX plants is closely associated to the cost of hydrogen (i.e., electrolysis capital cost, electricity cost, and capacity factor) and such systems cannot rely only on green hydrogen from the low expected amounts of excess electricity from intermittent renewables. Summary: In this work, through a simplified economic analysis, the region of competitiveness of this class of plants compared to other possible uses of biomass has been qualitatively identified. The research gaps mainly lie in the lack of assessments on the design and operating criteria of flexible PBtX plants and of studies providing insights on the value of flexibility for a PBtX plant, when integrated in the electric energy systems of the future
Torsadogenic risk of antipsychotics : combining adverse event reports with drug utilization data across Europe
No full textAntipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥ 4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled) to group E (unclear/uncertain signal: only 2/5 criteria). Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID). Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone). In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia) to 13.99 (France, 2009). Considerable increment of Group A agents was found in several Countries (+3.47 in France): the exposure to olanzapine increased across all Countries (+1.84 in France) and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009). Among Group B drugs, levomepromazine peaked 3.78 (Serbia); fluphenazine 1.61 (Slovenia). This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and Country-specific scenarios requiring potential regulatory consideration: levomepromazine (Serbia), fluphenazine (Slovenia), olanzapine (across Europe), cyamemazine (France). This synergy should be encouraged to support future pharmacovigilance activities
38. A new economical and environmentally friendly synthesis of 2,5-dimethyl-2,4-hexadiene
No full textA new vapor phase process for the synthesis of 2,5-dimethyl-2,4-hexadiene (or tetramethyl-butadiene) by dehydration of 2,5-dimethyl-2,4-hexadiiol on solid acid catalysts is described. This synthesis is an interesting example of an economical and environmentally friendly process of industrial interest
Discontinuation of and changes in drug therapy for hypertension among newly-treated patients: a population-based study in Italy
No full textOBJECTIVES:
To assess rates and determinants of treatment discontinuation of or changes in initial antihypertensive drug therapy in a large cohort of patients from Lombardia (Italy).
METHODS:
The cohort included 445356 patients aged 40 -80 years who received their first antihypertensive drug prescription (monotherapy) during 1999--2002. Discontinuation was defined by the absence of any antihypertensive prescription during a 90-day period following the end of the latest prescription. If during the same period a drug of a different class was added or replaced the initial prescription, treatment modification was regarded as combination or switching, respectively. Competing risks methodology was used to estimate and compare cause-specific cumulative incidence.
RESULTS:
Cumulative incidences of discontinuation, combination and switching were respectively 33, 14 and 15% at 6 months, 41, 18 and 17% at 1 year, and 50, 25 and 19% at 5 years since initial treatment. Compared with patients starting treatment with angiotensin-converting enzyme inhibitors, the rate of discontinuation was less for patients on angiotensin receptor blockers with a hazard ratio of 0.92 (95% confidence interval =0.90-0.94), whereas increased discontinuation was observed for patients starting with other drugs, mainly beta-blockers with a hazard ratio of 1.64 (1.62-1.67); and diuretics with a hazard ratio of 1.83 (1.81-1.85).
CONCLUSION:
In the general population of Lombardia, discontinuation of the initial single antihypertensive drug treatment is a common phenomenon, whereas switching to another monotherapy and to combination treatment occur at similarly much lower rates. Blockers of the renin-angiotensin system are associated with the lowest incidence of treatment discontinuation
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