Electrochemical remediation of phenol contaminated kaolin under low-strength electric fields

Soil degradation is a global concern. Electrochemical remediation (ER) technology is considered an appealing strategy for soil remediation because it is a low-cost, adaptable, and effective noninvasive in situ technology. Currently, the remediation of soil characterized by fine grains, low-hydraulic permeability, heterogeneous conditions, and mixtures of contaminants is still challenging since other conventional technologies are poorly effective. ER of soil is based on the application of low potentials between a couple of electrodes which induces an electric field (E) in the contaminated field. In this work, very low values of electric field (E ≤ 0.25 V cm−1) were used for the ER of contaminated kaolin. Phenol was selected as model hazardous organic compound and kaolin as model, reproducible and low buffering and low permeability clay. The effect of several factors, including the nature of the electrodes, treatment time, kind of current, the strength of the E and the nature of supporting electrolyte, on the performance of the process was investigated in detail and discussed in terms of the normalized phenol concentration and its total removal from the kaolin. Overall, the main finding is that the use of very low value of E (0.15 V cm−1) can allow to simultaneously desorb, mobilize and also in-situ degrade phenol. The highest removals of phenol up to approximately 80% and 90% from the kaolin under both direct and sinusoidal E, respectively, were reached using compact graphite as electrodes in presence of Na2SO4 into the kaolin

Electrochemical remediation of kaolin-soil contaminated by phenol: effect of several operative parameters

Electrochemical remediation technology is considered an appealing strategy for the remediation of fine- grained soils, characterized by a low hydraulic conductivity and large specific surface area, contaminated with inorganic, organic, and mixed pollutants. In both Electrokinetic (EK) and Electrochemical Geo-Oxidation (ECGO) technologies, an electric field is imposed on the contaminated soil to remove the pollutants by the combined mechanisms of electroosmosis, electromigration, and/or electrophoresis. Moreover, ECGO uses low voltage and both direct and alternating amperage (DC/AC) applied in a proprietary series to induce reduction-oxidation reactions on soil surfaces at the micro-scale. According to the literature, in this method, each soil particle acts as a micro-capacitor that charges and discharges in a cyclic fashion. The energy burst on discharge at the micro-scale is intense, theoretically allowing the conversion of most organic contaminants to carbon dioxide and water near the conducting particle surface [2-4]. However, the effectiveness of the technology strongly depends on the physical-chemical states of the soils and the contaminants, pH, sorption of contaminants on soil particle surfaces and different effects induced by the hydrogen ions and hydroxide ions generated at the electrodes. In this work, the effect of several factors, including the intensity and mode of the applied electric field, duration of treatment, nature of supporting electrolytes, on the electrochemical remediation of kaolin-soil contaminated by phenol (200 mgPhenol/kgsoil) was investigated. It was found that a proper selection of the operative parameters is the key- factor to improve the electrochemical remediation of the contaminated soil. High removal of phenol from the kaolin up to 88% was achieved after 93 hours of treatment using graphite electrodes and a gradient electric field of 0.15 V cm-1. [1] A. T. Yeung et al. J. Hazard. Mater. 2011, 195, 11 [2] D. Rahner et al. Electrochim. Acta 2002, 47, 1395 [3] J. Röhrs et al. Electrochim. Acta 2002, 47, 1405 [4] L.M. Zanko et al. Electrochim. Acta 2020, 354, 13669

Efficacy of bezlotoxumab in participants receiving metronidazole, vancomycin, or fidaxomicin for treatment of Clostridioides (Clostridium) difficile infection

Background: In phase 3 MODIFY I/II trials, bezlotoxumab significantly reduced recurrence of Methods: In MODIFY I/II (NCT01241552/NCT01513239), participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment. Using pooled data from MODIFY I/II, initial clinical cure (ICC) and rCDI were assessed in metronidazole-, vancomycin-, and fidaxomicin-treated subgroups. Results: Of 1554 participants in MODIFY I/II, 753 (48.5%) received metronidazole, 745 (47.9%) vancomycin, and 56 (3.6%) fidaxomicin. Fewer participants receiving metronidazole had a prior CDI episode in the previous 6 months (12.9%) or ≥1 risk factor for rCDI (66.0%) vs participants receiving vancomycin (41.2% and 83.6%, respectively) and fidaxomicin (55.4% and 89.3%, respectively). ICC rates were similar in the bezlotoxumab (metronidazole, 81.0%; vancomycin, 78.5%; fidaxomicin, 86.7%) and placebo groups (metronidazole, 81.3%; vancomycin, 79.6%; fidaxomicin, 76.9%). In placebo-treated participants, the rCDI was lower in the metronidazole subgroup vs the vancomycin and fidaxomicin subgroups (metronidazole, 28.0%; vancomycin, 38.4%; fidaxomicin, 35.0%). When analyzed by subsets based on history of CDI, rCDI rates were similar in the metronidazole and vancomycin groups. rCDI rates were lower in all antibiotic subgroups for bezlotoxumab vs placebo (metronidazole: rate difference [RD], -9.7%; 95% confidence interval [CI], -16.4% to -3.1%; vancomycin: RD, -15.4%; 95% CI, -22.7% to -8.0%; fidaxomicin: RD, -11.9%; 95% CI, -38.1% to 14.3%). Conclusion: Bezlotoxumab reduces rCDI vs placebo in participants receiving metronidazole and vancomycin, with a similar effect size in participants receiving fidaxomicin

The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2.

BACKGROUND: A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling. RESULTS: Administration of DS (25 mg/kg/day, intraperitoneal) in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2. CONCLUSIONS: Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.journal articleresearch support, non-u.s. gov't2012 Sep 182012 09 18importe

Small firms and patenting revisited

In order to observe a patent application at the firm level two conditions need to be met: new products need to be of patentable quality, which depends both on the degree of novelty of innovations and on the total number (portfolio) of innovations; and the benefits of patents need to be higher than the costs of owning them. Analyzing the patent propensity of small and large UK firms using a novel innovation-level survey (the SIPU survey) linked to Community Innovation Survey data we find that when we consider the whole innovation portfolio smaller firms do patent less than larger firms. However, using data on individual innovations, we find that smaller firms are no less likely to patent any specific innovation than larger firms. We argue that size differences in the probability to patent relate primarily to the ‘portfolio effect’, i.e. larger firms generate more innovations than smaller firms and therefore are more likely to create one or more which are patentable. As for the decision to patent a patentable innovation, we find that cost barriers, more than issues of innovation quality or enforceability, deter small firms from patenting specific innovations. Measures to address the costs of patenting for smaller firms – perhaps by considering patents as eligible costs for R&D tax credits – and/or subsidizing SMEs’ participation in IP litigation schemes may both encourage patent use by smaller firms

Pain shared, pain halved? Cooperation as a coping strategy for innovation barriers

The paper analyses the relationship between the perception of barriers to innovation and the firm’s propensity to cooperate to mitigate their effect. First, we look at whether cooperation with research organizations or private firms is associated with experiencing different types of barriers, for example, financial constraints, lack of human capital or uncertain market demand. Second, we test whether experiencing several types of barriers simultaneously has a super-modular effect on the propensity to cooperate tout court, and the choice of cooperation partner. We find that having to face a single, specific constraint leads to firms ‘sharing the pain’ with cooperation partners—both research organization and other firms. However, the results of a super-modularity test show that having to cope with different barriers is a deterrent to establishing cooperation agreements, especially when firms lack finance, adequate skills and information on technology or markets. The paper adds to the innovation literature by identifying the factors associated with firms’ coping with different barriers by applying a selective cooperation strategy

In vitro inhibition of porcine cytochrome P450 by 17β -estradiol and 17α-estradiol

Sexually mature pigs are known to possess high concentrations of testicular steroids, which have been shown to change the activities of cytochrome P450 in vitro. The aim of the present study was to evaluate the regulation of CYP1A and CYP2E1 activity by the steroids dihydrotestosterone (DHT), 3β-androstenol, 17β-estradiol and 17α-estradiol. Catalytic activities of 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) were used as markers of CYP1A activities, while p-nitrophenol hydroxylase (PNPH) was used as a marker of CYP2E1 activities. Of the steroids tested, only 17β-estradiol and 17α-estradiol inhibited EROD and MROD activities. This inhibition was observed when a steroid concentration of 100 µM was used, while lower concentrations showed no inhibitory effect. PNPH activities were inhibited only by 100 µM of 17β-estradiol. The significance of these results in vivo is unknown because inhibition was only found when concentrations of estrogens higher than physiological levels were used. Nevertheless, the results provided further evidence on the important role of estrogens in regulation of porcine cytochrome P450 activities

Clinical Relevance of Dissolution Testing in Quality by Design

Quality by design (QbD) has recently been introduced in pharmaceutical product development in a regulatory context and the process of implementing such concepts in the drug approval process is presently on-going. This has the potential to allow for a more flexible regulatory approach based on understanding and optimisation of how design of a product and its manufacturing process may affect product quality. Thus, adding restrictions to manufacturing beyond what can be motivated by clinical quality brings no benefits but only additional costs. This leads to a challenge for biopharmaceutical scientists to link clinical product performance to critical manufacturing attributes. In vitro dissolution testing is clearly a key tool for this purpose and the present bioequivalence guidelines and biopharmaceutical classification system (BCS) provides a platform for regulatory applications of in vitro dissolution as a marker for consistency in clinical outcomes. However, the application of these concepts might need to be further developed in the context of QbD to take advantage of the higher level of understanding that is implied and displayed in regulatory documentation utilising QbD concepts. Aspects that should be considered include identification of rate limiting steps in the absorption process that can be linked to pharmacokinetic variables and used for prediction of bioavailability variables, in vivo relevance of in vitro dissolution test conditions and performance/interpretation of specific bioavailability studies on critical formulation/process variables. This article will give some examples and suggestions how clinical relevance of dissolution testing can be achieved in the context of QbD derived from a specific case study for a BCS II compound

Drug Absorption Modeling as a Tool to Define the Strategy in Clinical Formulation Development

The purpose of this mini review is to discuss the use of physiologically-based drug absorption modeling to guide the formulation development. Following an introduction to drug absorption modeling, this article focuses on the preclinical formulation development. Case studies are presented, where the emphasis is not only the prediction of absolute exposure values, but also their change with altered input values. Sensitivity analysis of technologically relevant parameters, like the drug’s particle size, dose and solubility, is presented as the basis to define the clinical formulation strategy. Taking the concept even one step further, the article shows how the entire design space for drug absorption can be constructed. This most accurate prediction level is mainly foreseen once clinical data is available and an example is provided using mefenamic acid as a model drug. Physiologically-based modeling is expected to be more often used by formulators in the future. It has the potential to become an indispensable tool to guide the formulation development of challenging drugs, which will help minimize both risks and costs of formulation development