PLASTICS RECOVERY FROM MUNICIPAL WASTE: MAINSTREAMS AND BY-PRODUCTS IN A CASE STUDY IN NORTHERN ITALY.

In the case study dealt with here, the factory treatments of dry Municipal Solid Waste are aimed primarily at materials recovery; restraining energy recovery to the hardly recyclable by-products. The main input consists of the so-called multipak from MSW source-sorted collection; plus packaging waste, paper and cardboard and other similar waste from curb-side collection. The principal fractions produced by the selection plant, own and operated by the Public Company in charge of MSW management, in the Year 2012 were 27 064 tonnes of plastics, 5 066 of paper, 3 014 of tin coated steel and 4 886 tonnes of extraneous fraction to dispose of. A minor – though valuable – product was aluminium. The immediate energy consumption indices were calculated for multipak processed in the factory; the homogeneous overall index is 238 MJ / t

Health Care Waste production: measures and estimates in “V. Cervello” Hospital, Palermo, Italy.

A monitoring work was carried out in May/June 2007 in one large hospital located in Palermo. The monitoring consisted in weighing the infectious waste containers filled in some Departments purposely chosen. As a second stage of the work a comparison was attempted between the results obtained from the waste production monitoring and the Hospital’s purchases recorded in the same time. A restricted list of purchased products out of the general one was extracted. Such list allows one to calculate approximately the mass of medical devices purchased and their composition. To these materials a reasonable change in humidity after use was attributed. It was possible in this deductive way to draw a probable amount and composition of waste materials really arising from health care activities (commonly – though not rigorously – considered all infectious), whose characters is forbidden to ascertain by direct inspection

A LAB-SCALE MICROWAVE SYSTEM FOR EXPERIMENTS OF HIGH TEMPERATURE WASTE PYROLYSIS

The reactor designed and assembled at Università degli Studi di Palermo - presented here - was conceived to explore high unit power input, high temperature reductive processes. Its main field of use therefore is likely to be the destruction of liquid waste fed as an aerosol; or of VOCs; or of granular waste making a fluidized bed. If required, a 3 - phase system including a solid catalyst could also be set up. These waste should be free of low - melting or boiling metals. Incidentally, a literature review shows that the compounds taken as benchmark in thermal VOC destruction are trichloroethylene, benzene and toluene. At lower unit power rates this MW - based system lends itself also to recovering useful fractions from complex waste like WEEE (Waste of Electrical and Electronic Equipment), through pyrolysis and gasification

Experimental sorting of municipal-like waste in the hospital “Civico”, Palermo (IT)

An experiment of source sorting - based management of Health Care Waste (HCW) was carried out in 2011 in 4 Departments of the Public Hospital “Civico” (Palermo, IT), where the basic mandatory separation between hazardous and non-hazardous waste was already going on since year 2000.The experiment consisted in weighing every day for 15 days 4 predefined fractions collected in the Infirmaries (namely paper, plastics, glass and unsorted fraction), and the bags with unsorted waste from the patient’s stay room. Furthermore, in 1 of the 4 Departments also the boxes of Infectious Waste (IW)were weighed for a week.As a result a weighted average value of 0.56 kg of Municipal-like Waste (MLW) per bed and per day was obtained for the Infirmaries of the 4 Departments (1.89 kg for the whole Department). The potentially recoverable waste fractions of MLW were about 65.7 %, the balance being unsorted waste.The actual production of IW − monitored in just one of the Departments, OU 1− brought to a generation rate of 0.74 kg/bed-day with a range 0.50−1.00. This production represents the 54 % of total waste from that Infirmary but just 34 % of the overall waste stream from the Unit. This pilot experiment confirms the wide finding that IW are a minor part of the overall waste stream produced in a health care structure

Materials recovery from WEEE: current situation in Sicily.

The potential recovery of materials and energy in one year in Italy and in Sicily was estimated assuming that all WEEEs were gathered through the collection – treatment – disposal system implemented according to the rules in force. The embodied energy (EE) recovery associated to material recovery was also estimated, starting from standard values of EE and from yields declared for each component. Mass fractions composition for some categories of WEEE given by a facility in Catania agree with the national averages. Starting from data given by another facility - located in Siracusa - which processes all the five R categories (R1 to R5), potential mass and energy recovery was estimated for this plant. The results compared with national estimates lead to the conclusion that currently this plant contributes by 6% as mass and by 5% for EE recovery. National figures for potential energy recovery from WEEE shows that 10 670 GWh could be theoretically recovered, that is as much as the energy used for civil needs in Italy by two millions people / yr

Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial.

BACKGROUND: Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines. METHODS: We enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events (AEs). Immunogenicity was evaluated using IFNγ enzyme-linked immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines. RESULTS: The vaccines were well tolerated in all age groups with no vaccine-related serious AEs. High-level TRAP-specific IgG and T cell responses were generated after boosting with MVA. CD8+ T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly. CONCLUSION: Malaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations. CLINICAL TRIAL REGISTRATION: The clinical trial was registered on http://Clinicaltrials.gov (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217)

Novel human anti-claudin 1 mAbs inhibit hepatitis C virus infection and may synergize with anti-SRB1 mAb

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and liver carcinoma and new therapies based on novel targets are needed. The tight junction protein claudin 1 (CLDN-1) is essential for HCV cell entry and spread, and anti-CLDN-1 rat and mouse mAbs are safe and effective in preventing and treating HCV infection in a human liver chimeric mouse model. To accelerate translation of these observations into a novel approach to treat HCV infection and disease in humans, we screened a phage display library of human single-chain antibody fragments by using a panel of CLDN-1-positive and -negative cell lines and identified phage specifically binding to CLDN-1. The 12 clones showing the highest levels of binding were converted into human IgG4. Some of these mAbs displayed low-nanomolar affinity, and inhibited infection of human hepatoma Huh7.5 cells by different HCV isolates in a dose-dependent manner. Cross-competition experiments identified six inhibitory mAbs that recognized distinct epitopes. Combination of the human anti-SRB1 mAb C-1671 with these anti-CLDN-1 mAbs could either increase or reduce inhibition of cell culture-derived HCV infection in vitro. These novel human anti-CLDN-1 mAbs are potentially useful to develop a new strategy for anti-HCV therapy and lend support to the combined use of antibodies targeting the HCV receptors CLDN-1 and SRB1, but indicate that care must be taken in selecting the proper combination

Anti-EphA2 Antibodies with Distinct In Vitro Properties Have Equal In Vivo Efficacy in Pancreatic Cancer

The EphA2 receptor tyrosine kinase is overexpressed in a variety of human epithelial cancers and is a determinant of malignant cellular behavior in pancreatic adenocarcinoma cells. Moreover, it is expressed in tumor endothelium and its activation promotes angiogenesis. To better clarify the therapeutic potential of monoclonal antibodies (mAbs) directed to the EphA2 receptor, we generated a large number of mAbs by differential screening of phage-Ab libraries by oligonucleotide microarray technology and implemented a strategy for the rapid identification of antibodies with the desired properties. We selected two high-affinity and highly specific EphA2 monoclonal antibodies with different in vitro properties on the human pancreatic tumor cell line MiaPaCa2. One is a potent EphA2-agonistic antibody, IgG25, that promotes receptor endocytosis and subsequent degradation, and the second is a ligand antagonist, IgG28, that blocks the binding to ephrin A1 and is cross-reactive with the mouse EphA2 receptor. We measured the effect of antibody treatment on the growth of MiaPaCa2 cells orthotopically transplanted in nude mice. Both IgG25 and IgG28 had strong antitumor and antimetastatic efficacy. In vivo treatment with IgG25 determined the reduction of the EphA2 protein levels in the tumor and the phosphorylation of FAK on Tyr576 while administration of IgG28 caused a decrease in tumor vascularization as measured by immunohistochemical analysis of CD31 in tumor sections. These data show that in a pancreatic cancer model comparable therapeutic efficacy is obtained either by promoting receptor degradation or by blocking receptor activation

A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection

Background: Nearly 3 million people worldwide are coinfected with HIV and HCV. Affordable strategies for prevention are needed. We developed a novel vaccination regimen involving replication-defective and serologically distinct chimpanzee adenovirus (ChAd3, ChAd63) vector priming followed by modified vaccinia Ankara (MVA) boosts, for simultaneous delivery of HCV non-structural (NSmut) and HIV-1 conserved (HIVconsv) region immunogens.Methods: We conducted a phase I trial in which 33 healthy volunteers were sequentially enrolled and vaccinated via the intramuscular route as follows: 9 received ChAd3-NSmut [2.5 × 1010 vp] and MVA-NSmut [2 × 108 pfu] at weeks 0 and 8, respectively; 8 received ChAdV63.HIVconsv [5 × 1010 vp] and MVA.HIVconsv [2 × 108 pfu] at the same interval; 16 were co-primed with ChAd3-NSmut [2.5 × 1010 vp] and ChAdV63.HIVconsv [5 × 1010 vp] followed at week 8 by MVA-NSmut and MVA.HIVconsv [both 1 × 108 pfu]. Immunogenicity was assessed using peptide pools in ex vivo ELISpot and intracellular cytokine assays. Vaccine-induced whole blood transcriptome changes were assessed by microarray analysis.Results: All vaccines were well tolerated and no vaccine-related serious adverse events occurred. Co-administration of the prime-boost vaccine regimens induced high magnitude and broad T cell responses that were similar to those observed following immunization with either regimen alone. Median (interquartile range, IQR) peak responses to NSmut were 3,480 (2,728–4,464) and 3,405 (2,307–7,804) spot-forming cells (SFC)/106 PBMC for single and combined HCV vaccinations, respectively (p = 0.8). Median (IQR) peak responses to HIVconsv were 1,305 (1,095–4,967) and 1,005 (169–2,482) SFC/106 PBMC for single and combined HIV-1 vaccinations, respectively (p = 0.5). Responses were maintained above baseline to 34 weeks post-vaccination. Intracellular cytokine analysis indicated that the responding populations comprised polyfunctional CD4+ and CD8+ T cells. Canonical pathway analysis showed that in the single and combined vaccination groups, pathways associated with antiviral and innate immune responses were enriched for upregulated interferon-stimulated genes 24 h after priming and boosting vaccinations.Conclusions: Serologically distinct adenoviral vectors encoding HCV and HIV-1 immunogens can be safely co-administered without reducing the immunogenicity of either vaccine. This provides a novel strategy for targeting these viruses simultaneously and for other pathogens that affect the same populations.Clinical trial registration:https://clinicaltrials.gov, identifier: NCT0236221

Targeting a host-cell entry factor barricades antiviral-resistant HCV variants from on-therapy breakthrough in human-liver mice

Objective: Direct-acting antivirals (DAAs) inhibit hepatitis C virus (HCV) infection by targeting viral proteins that play essential roles in the replication process. However, selection of resistance-associated variants (RAVs) during DAA therapy has been a cause of therapeutic failure. In this study, we wished to address whether such RAVs could be controlled by the co-administration of host-targeting entry inhibitors that prevent intrahepatic viral spread. Design: We investigated the effect of adding an entry inhibitor (the anti-scavenger receptor class B type I mAb1671) to a DAA monotherapy (the protease inhibitor ciluprevir) in human-liver mice chronically infected with HCV of genotype 1b. Clinically relevant non-laboratory strains were used to achieve viraemia consisting of a cloud of related viral variants (quasispecies) and the emergence of RAVs was monitored at high resolution using next-generation sequencing. Results: HCV-infected human-liver mice receiving DAA monotherapy rapidly experienced on-therapy viral breakthrough. Deep sequencing of the HCV protease domain confirmed the manifestation of drug-resistant mutants upon viral rebound. In contrast, none of the mice treated with a combination of the DAA and the entry inhibitor experienced on-therapy viral breakthrough, despite detection of RAV emergence in some animals. Conclusions: This study provides preclinical in vivo evidence that addition of an entry inhibitor to an anti-HCV DAA regimen restricts the breakthrough of DAA-resistant viruses. Our approach is an excellent strategy to prevent therapeutic failure caused by on-therapy rebound of DAA-RAVs. Inclusion of an entry inhibitor to the newest DAA combination therapies may further increase response rates, especially in difficult-to-treat patient populations