An Analysis of International Health Regulations Emergency Committees and Public Health Emergency of International Concern Designations

Nine public health events have been assessed for the potential declaration of a Public Health Emergency of International Concern (PHEIC). According to the World Health Organization (WHO) International Health Regulations (IHR), a PHEIC is defined as an extraordinary event that constitutes a public health risk to other states through international spread and requires a coordinated international response. The WHO Director-General convenes Emergency Committees (ECs) to provide their advice on whether an event constitutes a PHEIC. The EC rationales have been continuously criticised for being non-transparent and contradictory to the IHR. This first comprehensive analysis of EC rationale provides recommendations to increase clarity of EC decisions which will strengthen the IHR and WHO’s legitimacy in future outbreaks. A total of 66 EC statements were reviewed from the nine public health outbreaks of influenza A, Middle East respiratory syndrome coronavirus, polio, Ebola virus disease, Zika, yellow fever and coronavirus disease-2019 (COVID-19). Statements were analysed to determine which of the three IHR criteria were noted as contributing towards the EC’s justification on whether to recommend to the WHO Director-General that a PHEIC be declared and what language was used to explain their decision. Interpretation of the criteria were often vague and applied inconsistently. ECs often failed to describe and justify which criteria had been satisfied. Guidelines must be developed for the standardised interpretation of IHR core criteria. The ECs must clearly identify and justify which criteria have contributed to their rationale for or against PHEIC declaration. Striving for more consistency and transparency in EC justifications would benefit future deliberations and provide more understanding and support for the process

Cancer incidence in Priolo, Sicily: a spatial approach for estimation of industrial air pollution impact

The territory around the industrial Sicilian area of Priolo, Italy, has been defined as a contaminated site (CS) of national priority for remediation because of diffuse environmental contamination caused by large industrial settlements. The present study investigates the spatial distribution of cancer into the CS territory (period 1999-2006). Different geographical methods used for the evaluation of the impact of industrial air pollutants were adopted. Using the database of Syracuse Province Cancer Registry, gender-specific standardised incidence ratios were calculated for 35 tumour sites for the CS overall and for each municipality included in the CS. A cluster analysis for 17 selected neoplasms was performed at micro-geographical level. The identification of the priority index contaminants (PICs) present in environmental matrices and a review of their carcinogenicity have been performed and applied in the interpretation of the findings. The area has a higher cancer incidence with respect to the provincial population, in particular excess is registered among both genders of lung, bladder and breast cancers as well as skin melanoma and pleural mesothelioma and there is an a priori evidence of association with the exposure to PICs. The study highlights the need to provide different approaches in CSs where several exposure pathways might be relevant for the population. The presence of potential sources of asbestos exposure deserves specific concern

Exosomes From Human Cardiac Progenitor Cells for Therapeutic Applications: Development of a GMP-Grade Manufacturing Method

Exosomes, nanosized membrane vesicles secreted by cardiac progenitor cells (Exo-CPC), inhibit cardiomyocyte apoptosis under stress conditions, promote angiogenesis in vitro, and prevent the early decline in cardiac function after myocardial infarction in vivo in preclinical rat models. The recognition of exosome-mediated effects has moved attempts at developing cell-free approaches for cardiac repair. Such approaches offer major advantages including the fact that exosomes can be stored as ready-to-use agents and delivered to patients with acute coronary syndromes. The aim of the present work was the development of a good manufacturing practice (GMP)-grade method for the large-scale preparation of Exo-CPC as a medicinal product, for a future clinical translation. A GMP-compliant manufacturing method was set up, based on large-scale cell culture in xeno-free conditions, collection of up to 8 l of exosome-containing conditioned medium and isolation of Exo-CPC through tangential flow filtration. Quality control tests were developed and carried out to evaluate safety, identity, and potency of both cardiac progenitor cells (CPC) as cell source and Exo-CPC as final product (GMP-Exo-CPC). CPC, cultured in xeno-free conditions, showed a lower doubling-time than observed in research-grade condition, while producing exosomes with similar features. Cells showed the typical phenotype of mesenchymal progenitor cells (CD73/CD90/CD105 positive, CD14/CD20/CD34/CD45/HLA-DR negative), and expressed mesodermal (TBX5/TBX18) and cardiac-specific (GATA4/MESP1) transcription factors. Purified GMP-Exo-CPC showed the typical nanoparticle tracking analysis profile and expressed main exosome markers (CD9/CD63/CD81/TSG101). The GMP manufacturing method guaranteed high exosome yield (>1013 particles) and consistent removal (≥97%) of contaminating proteins. The resulting GMP-Exo-CPC were tested for safety, purity, identity, and potency in vitro, showing functional anti-apoptotic and pro-angiogenic activity. The therapeutic efficacy was validated in vivo in rats, where GMP-Exo-CPC ameliorated heart function after myocardial infarction. Our standardized production method and testing strategy for large-scale manufacturing of GMP-Exo-CPC open new perspectives for reliable human therapeutic applications for acute myocardial infarction syndrome and can be easily applied to other cell sources for different therapeutic areas

Marketing to families with children in tourism

The thesis introduces family tourism in the marketing studies by providing a multiple-facet approach and deepening the investigation by examining the museum set, a context worth for tourism, leisure, and public policie