Citizen science in environmental health research: A comparison with conventional approaches and creation of a guidance tool issued from the LILAS initiative.

CONTEXT: Public interest for citizen science (CS) in environmental health is growing. The goals of environmental health research projects are diverse, as are the methods used to reach these goals. Opportunities for greater implication of the civil society and related challenges differ at each step of such projects. These methodological aspects need to be widely shared and understood by all stakeholders. The LILAS initiative (acronym for "application of citizen science approaches such as LIving LAbS to research on environmental exposures and chronic risks") aimed to 1) favor a mutual understanding of the main issues and research methods in environmental health, of their stakes for different actors, but also of the requirements, strengths and limitations of these methods and to 2) identify expected benefits and points of attention related to stronger degrees of participation as part of environmental health research projects. METHODS: The LILAS initiative gathered institutional researchers, academics and civil society representatives interested in environmental exposures. Five meetings allowed to collectively identify different types of environmental health research studies and reflect about the benefits, limitations, and methodological issues related to the introduction of growing citizen participation as part of such studies. An analytic table matrix summarizing these aspects was co-created and filled by participants, as a tool devoted to help stakeholders with the definition of future CS research projects in environmental health. RESULTS: For different fields of research (e.g.: studies for assessment of environmental exposures, interventions on these exposures, quantitative risk assessment, epidemiological studies), the matrix lists expected benefits for various stakeholders, the fundamental principles of research methods and related practical constraints, but also advantages and limitations related to the use of CS or conventional research approaches. CONCLUSION: The LILAS initiative allowed to develop a tool which provides consolidated grounds for the co-creation of research projects on environmental exposures involving CS.

Resilience after a nuclear accident: readiness in using mobile phone applications to measure radiation and health indicators in various groups (SHAMISEN SINGS project).

An anonymous web-based survey was developed to check different aspects (SHAMISEN SINGS project): stakeholder awareness and perceptions of available mobile applications (apps) for measuring ionising radiation doses and health/well-being indicators; whether they would be ready to use them in the post-accidental recovery; and what are their preferred methodologies to acquire information etc. The results show that participation of the citizens would be most beneficial during post-accident recovery, providing individual measurements of external ionizing dose and health/well-being parameters, with possible follow-up. Also, participants indicated different preferences for sources to gain knowledge on ionising radiation and for the functions that an ideal app should have. The level of awareness and readiness to use apps to measure ionising radiation dose depended on two main aspects: individual differences (age & gender) and whether people were from countries affected by the previous major accidents. We concluded that stakeholders could have benefits from the data management plan: (1) it potentiates resilience at individual and community level; (2) citizens' measurements contribute to environmental monitoring and public health screening; (3) linkages between different types of data (environmental exposure, individual behavioural diaries, and measurements of health indicators) allow to perform more rigorous epidemiological studies.

Factors explaining the shortage and poor retention of qualified health workers in rural and remote areas of the Kayes, region of Mali: a qualitative study.

INTRODUCTION: Shortage of health workers is a worldwide problem but is particularly critical in sub-Saharan Africa. In Mali, the number of health workers is insufficient and their retention is low, particularly in rural and remote areas. Rural postings are unattractive to health workers. Very few studies have examined the factors contributing to the shortage and poor retention of health workers in Mali. The objective of this study is to identify and understand these factors with regards to skilled health workers in two rural health districts (Yélimané and Bafoulabé) in the region of Kayes, Mali. METHODS: This qualitative study is based on the conceptual framework of Lehman, Dieleman and Martineau. Data were collected through 46 in-depth interviews with health workers and decision-makers. A thematic content analysis was conducted with the support of QDA Miner software. RESULTS: The study identified factors contributing to the insufficient allocation and poor retention of rural health workers in these districts. They are individual-level factors (gender, family situation, age), unattractive living and working conditions, community recognition and participation, quality of leadership, an unfavourable recruitment/assignment process and insufficient financial incentives. It shows that female staff have specific constraints that prevent them from deploying to or staying in rural areas for long periods. In addition, the number of staff recruited at the national level is unpredictable and insufficient, while their recruitment and assignment process is perceived to be inequitable and not very transparent, disadvantaging rural health structures. Some strategies were identified to improve the availability and retention of health workers in these areas. They take into account certain social norms, notably gender roles, and include the improvement of living and working conditions, as well as the strengthening of health workforce management. CONCLUSION: This study's findings highlight the multifaceted nature of factors contributing to the availability and retention of health workers in rural and remote areas of sub-Saharan Africa and the challenges associated with them. This study identifies some strategies that can be combined to facilitate the retention and availability of health workers in these areas. Some strategies involve actors outside the health sector, requiring joint efforts for their implementation. This research provides decision-makers with evidence to support informed decision making with regards to the retention of health workers in rural areas.

Living conditions and health status of populations living in territories impacted by nuclear accidents - Some lessons for developing health surveillance programme.

This paper explores how health concerns of populations living in contaminated areas following radiological accidents can be considered in developing health surveillance. The research was performed in the framework of the SHAMISEN project, and aimed at identifying the impacts on, and challenges associated with, living and social conditions of affected populations. These objectives were achieved through the analysis of specific Case Studies in different situations observed after the Chernobyl accident (Belarus and Norway) and the activities carried out after the Fukushima accident. It incorporates an analysis of testimonies of medical experts and local stakeholders from contaminated territories in Japan within two Case Studies as well as through a dedicated workshop jointly organised with Fukushima Medical University in Japan in March 2016. The analysis addresses the following topics:Thus, this paper outlines key lessons learned from each of these topics, by providing tangibles examples from the analysis of the various Case Studies.

Nuclear and Radiological Preparedness: The Achievements of the European Research Project PREPARE.

The PREPARE project aimed closing gaps identified in nuclear and radiological preparedness in Europe following the first evaluation of the Fukushima disaster. With 46 partners from Europe and Japan, it collected the key players in the area of emergency management and rehabilitation preparedness. Starting from February 2013, the project ended in January 2016. Among others, the project reviewed existing operational procedures for long-lasting releases, cross-border problems in radiation monitoring and food safety and further developed missing functionalities in decision support systems ranging from improved source term estimation and dispersion modelling to the inclusion of hydrological pathways for European water bodies. In addition, a so-called Analytical Platform has been developed to explore the scientific and operational means to improve information collection, information exchange and the evaluation of such types of disasters. The tools developed within the project will be partly integrated into the decision support systems ARGOS and JRODOS.

Hybrid antibacterials. DNA polymerase-topoisomerase inhibitors.

Novel Gram-positive (Gram+) antibacterial compounds consisting of a DNA polymerase IIIC (pol IIIC) inhibitor covalently connected to a topoisomerase/gyrase inhibitor are described. Specifically, 3-substituted 6-(3-ethyl-4-methylanilino)uracils (EMAUs) in which the 3-substituent is a fluoroquinolone moiety (FQ) connected by various linkers were synthesized. The resulting "AU-FQ" hybrid compounds were significantly more potent than the parent EMAU compounds as inhibitors of pol IIIC and were up to 64-fold more potent as antibacterials in vitro against Gram+ bacteria. The hybrids inhibited the FQ targets, topoisomerase IV and gyrase, with potencies similar to norfloxacin but 10-fold lower than newer agents, for example, ciprofloxacin and sparfloxacin. Representative hybrids protected mice from lethal Staphylococcus aureus infection after intravenous dosing, and one compound showed protective effect against several antibiotic-sensitive and -resistant Gram+ infections in mice. The AU-FQ hybrids are a promising new family of antibacterials for treatment of antibiotic-resistant Gram+ infections.

PREPARE: innovative integrated tools and platforms for radiological emergency preparedness and post-accident response in Europe.

The PREPARE project that started in February 2013 and will end at the beginning of 2016 aims to close gaps that have been identified in nuclear and radiological preparedness in Europe following the first evaluation of the Fukushima disaster. Among others, the project will address the review of existing operational procedures for dealing with long-lasting releases and cross-border problems in radiation monitoring and food safety and further develop missing functionalities in decision support systems (DSS) ranging from improved source-term estimation and dispersion modelling to the inclusion of hydrological pathways for European water bodies. In addition, a so-called Analytical Platform will be developed exploring the scientific and operational means to improve information collection, information exchange and the evaluation of such types of disasters. The tools developed within the project will be partly integrated into the two DSS ARGOS and RODOS.

An inquiry of the opinions of the French and Belgian populations as regards risk.

IRSN (France) and SCK-CEN (Belgium), two institutes of research and expertise in radiation protection and nuclear safety, simultaneously organised a very similar public opinion survey in their respective countries in November 2002. The study explores subjects such as: major people's concerns, perception of environmental risks, perception of risks in general, the role of experts in decision making, opinions on nuclear matters and aspects of nuclear emergency preparedness. In each country, more than 1000 citizens representing the general public have been consulted in face-to-face interviews. The field work has been performed by professional companies (BVA in France and Research International in Belgium). The paper shows that industrial and technological risks are not perceived as one of the major public concerns, although many other risks, of different nature are considered to be high. The actions of the authorities to provide protection against the consequences of many risks or disasters are not considered to be sufficient, and many respondents claim not to believe the information they receive. There exists a large difference between the opinion of French and Belgian public, and within the different language groups in Belgium, with regard to who should be in charge of the control of the hazardous industries. Many of the "actors" within the nuclear industry are not known by the respondents. The perception of the technical competence or the truth being told shows large variations between the main actors (such as members of the nuclear industry, the government or the media). Majorities within the population believe that a disaster as serious as the Chernobyl one can happen in their country and that in case of a nuclear accident, the authorities would not be capable to protect the population adequately.

Novel Quinoline-Based P2-P4 Macrocyclic Derivatives As Pan-Genotypic HCV NS3/4a Protease Inhibitors.

We have previously reported the discovery of our P2-P4 macrocyclic HCV NS3/4a protease inhibitor MK-5172, which in combination with the NS5a inhibitor MK-8742 recently received a breakthrough therapy designation from the US FDA for treatment of chronic HCV infection. Our goal for the next generation NS3/4a inhibitor was to achieve pan-genotypic activity while retaining the pharmacokinetic profile of MK-5172. One of the areas for follow-up investigation involved replacement of the quinoxaline moiety in MK-5172 with a quinoline and studying the effect of substitution at 4-position of the quinoline. The rationale for this effort was based on molecular modeling, which indicated that such modifications would improve interactions with the S2 subsite, in particular with D79. We wish to report herein the discovery of highly potent inhibitors with pan-genotypic activity and an improved profile over MK-5172, especially against gt-3a and A156 mutants.

Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure-activity relationships of the 7- and 5-, 6-, 8-positions.

As a continuation of our efforts to discover and develop the apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the SAR of 4-aryl-4H-chromenes with modifications at the 7- and 5-, 6-, 8-positions. It was found that a small hydrophobic group, such as NMe2, NH2, NHEt, and OMe, is preferred at the 7-position. Di-substitution at either the 5,7-positions or the 6,7-positions generally led to a large decrease in potency. Di-substitution at the 7,8-positions, in general, was found to result in potent compounds. 7-NMe2, 7-NHEt, 7-OMe, and 7,8-di-NH2 analogs were found to have similar SAR for the 4-aryl group, and several 7-substituted and 7,8-di-substituted analogs were found to have similar potencies as the lead compound MX58151 (2a) both as caspase activators and inhibitors of cell proliferation.