Application of ZnO nanoparticles in a self-cleaning coating on a metal panel: an assessment of environmental benefits

This article is focused on assessing environmental benefits of a self-cleaning coating (SCCs) containing nanoparticles (NPs) applied on metal panels. ZnO NPs are incorporated in the coating to enhance the level of hydrophobicity, which enables a dramatic reduction in the need for surface maintenance. The key question evaluated in this paper is whether the overall environmental performance of a nanobased SCC is better than the environmental performance of a coating without NPs. Much of the paper is dedicated to a comparison of advanced polyvinylidene fluoride (PVDF) protective coating with an alternative coating in which part of the PVDF is replaced by ZnO NPs. An integral part of the paper represents a detailed environmental assessment of the key ingredient of the nanoenhanced coating, ZnO NPs produced by large-scale supercritical hydrothermal synthesis developed within the Sustainable Hydrothermal Manufacturing of Nanomaterials (SHYMAN) project. LCA results show that the coating with NPs performs better than the coating without NPs in all assessed impact categories. This is due to the elimination of environmental impacts during the use stage where no maintenance is needed in the case of the coating with NPs. This reduction clearly outweighs the small additional environmental impacts of the production stage associated with the ZnO NPs

Sustainability assessment of continuous-flow hydrothermal synthesis of nanomaterials in the context of other production technologies

In this paper, we provide a comprehensive techno-economic and life cycle environmental evaluation of the continuous-flow hydrothermal synthesis (CFHS) of nanoparticles in the context of current production technologies. This method is compared with a set of competitor technologies: Plasma syntheses; Flame pyrolysis; Sol-gel synthesis; Batch Solvo/Hydrothermal syntheses; and Altair hydrochloride process. Technical criteria such as scale and variability of production and material properties are accounted for in the environmental and economic analyses. Case study nanomaterials are investigated with a range of potential applications: titanium dioxide (smart coatings, electronics, and water purification); zinc oxide (smart coatings, cosmetics); zirconium dioxide (nanocomposites, electronics); and lithium phosphate (lithium ion battery cathode material).Results show that CFHS can be ranked among the most productive methods capable of producing up to 100–250 kg/h of different types of high quality NPs dispersed in water. In terms of the environmental impacts, this newly developed technology does not use any toxic solvents, there are no emissions into the environment and the risk of leakage of NPs into environment is negligible. Comparison of values of selected environmental impact categories Cumulative Energy Demand (CED) and Global Warming Potential (GWP) shows that CFHS can compete with industrial technologies with low production variability and limited product quality (e.g. sulfate and chloride processes) and achieves much better results in comparison with technologies with similar variability (e.g. HT plasma or sol-gel) and product quality (sol gel). The same conclusion can be made in the case of an economic assessment. The combination of large scale and variability of production and quality of produced NPs can be considered as the major source of competitive potential of CFHS

FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer’s disease

Abstract Background Neurofibrillary pathology composed of tau protein is closely correlated with severity and phenotype of cognitive impairment in patients with Alzheimer’s disease and non-Alzheimer’s tauopathies. Targeting pathological tau proteins via immunotherapy is a promising strategy for disease-modifying treatment of Alzheimer’s disease. Previously, we reported a 24-week phase 1 trial on the active vaccine AADvac1 against pathological tau protein; here, we present the results of a further 72 weeks of follow-up on those patients. Methods We did a phase 1, 72-week, open-label study of AADvac1 in patients with mild to moderate Alzheimer’s disease who had completed the preceding phase 1 study. Patients who were previously treated with six doses of AADvac1 at monthly intervals received two booster doses at 24-week intervals. Patients who were previously treated with only three doses received another three doses at monthly intervals, and subsequently two boosters at 24-week intervals. The primary objective was the assessment of long-term safety of AADvac1 treatment. Secondary objectives included assessment of antibody titres, antibody isotype profile, capacity of the antibodies to bind to AD tau and AADvac1, development of titres of AADvac1-induced antibodies over time, and effect of booster doses; cognitive assessment via 11-item Alzheimer’s Disease Assessment Scale cognitive assessment (ADAS-Cog), Category Fluency Test and Controlled Oral Word Association Test; assessment of brain atrophy via magnetic resonance imaging (MRI) volumetry; and assessment of lymphocyte populations via flow cytometry. Results The study was conducted between 18 March 2014 and 10 August 2016. Twenty-six patients who completed the previous study were enrolled. Five patients withdrew because of adverse events. One patient was withdrawn owing to noncompliance. The most common adverse events were injection site reactions (reported in 13 [50%] of vaccinated patients). No cases of meningoencephalitis or vasogenic oedema were observed. New micro-haemorrhages were observed only in one ApoE4 homozygote. All responders retained an immunoglobulin G (IgG) antibody response against the tau peptide component of AADvac1 over 6 months without administration, with titres regressing to a median 15.8% of titres attained after the initial six-dose vaccination regimen. Booster doses restored previous IgG levels. Hippocampal atrophy rate was lower in patients with high IgG levels; a similar relationship was observed in cognitive assessment. Conclusions AADvac1 displayed a benign safety profile. The evolution of IgG titres over vaccination-free periods warrants a more frequent booster dose regimen. The tendency towards slower atrophy in MRI evaluation and less of a decline in cognitive assessment in patients with high titres is encouraging. Further trials are required to expand the safety database and to establish proof of clinical efficacy of AADvac1. Trial registration The studies are registered with the EU Clinical Trials Register and ClinicalTrials.gov: the preceding first-in-human study under EudraCT 2012-003916-29 and NCT01850238 (registered on 9 May 2013) and the follow-up study under EudraCT 2013-004499-36 and NCT02031198 (registered 9 Jan 2014), respectively

ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer’s disease

Alzheimer’s disease (AD) pathology is partly characterized by accumulation of aberrant forms of tau protein. Here we report the results of ADAMANT, a 24-month double-blinded, parallel-arm, randomized phase 2 multicenter placebo-controlled trial of AADvac1, an active peptide vaccine designed to target pathological tau in AD (EudraCT 2015-000630-30). Eleven doses of AADvac1 were administered to patients with mild AD dementia at 40 μg per dose over the course of the trial. The primary objective was to evaluate the safety and tolerability of long-term AADvac1 treatment. The secondary objectives were to evaluate immunogenicity and efficacy of AADvac1 treatment in slowing cognitive and functional decline. A total of 196 patients were randomized 3:2 between AADvac1 and placebo. AADvac1 was safe and well tolerated (AADvac1 n = 117, placebo n = 79; serious adverse events observed in 17.1% of AADvac1-treated individuals and 24.1% of placebo-treated individuals; adverse events observed in 84.6% of AADvac1-treated individuals and 81.0% of placebo-treated individuals). The vaccine induced high levels of IgG antibodies. No significant effects were found in cognitive and functional tests on the whole study sample (Clinical Dementia Rating-Sum of the Boxes scale adjusted mean point difference −0.360 (95% CI −1.306, 0.589)), custom cognitive battery adjusted mean z-score difference of 0.0008 (95% CI −0.169, 0.172). We also present results from exploratory and post hoc analyses looking at relevant biomarkers and clinical outcomes in specific subgroups. Our results show that AADvac1 is safe and immunogenic, but larger stratified studies are needed to better evaluate its potential clinical efficacy and impact on disease biomarkers