Public engagement on global health challenges

<p>Abstract</p> <p>Background</p> <p>Experience with public engagement activities regarding the risks and benefits of science and technology (S&T) is growing, especially in the industrialized world. However, public engagement in the developing world regarding S&T risks and benefits to explore health issues has not been widely explored.</p> <p>Methods</p> <p>This paper gives an overview about public engagement and related concepts, with a particular focus on challenges and benefits in the developing world. We then describe an Internet-based platform, which seeks to both inform and engage youth and the broader public on global water issues and their health impacts. Finally, we outline a possible course for future action to scale up this and similar online public engagement platforms.</p> <p>Results</p> <p>The benefits of public engagement include creating an informed citizenry, generating new ideas from the public, increasing the chances of research being adopted, increasing public trust, and answering ethical research questions. Public engagement also fosters global communication, enables shared experiences and methodology, standardizes strategy, and generates global viewpoints. This is especially pertinent to the developing world, as it encourages previously marginalized populations to participate on a global stage. One of the core issues at stake in public engagement is global governance of science and technology. Also, beyond benefiting society at large, public engagement in science offers benefits to the scientific enterprise itself.</p> <p>Conclusion</p> <p>Successful public engagement with developing world stakeholders will be a critical part of implementing new services and technologies. Interactive engagement platforms, such as the Internet, have the potential to unite people globally around relevant health issues.</p

Qualitative thematic analysis of consent forms used in cancer genome sequencing

<p>Abstract</p> <p>Background</p> <p>Large-scale whole genome sequencing (WGS) studies promise to revolutionize cancer research by identifying targets for therapy and by discovering molecular biomarkers to aid early diagnosis, to better determine prognosis and to improve treatment response prediction. Such projects raise a number of ethical, legal, and social (ELS) issues that should be considered. In this study, we set out to discover how these issues are being handled across different jurisdictions.</p> <p>Methods</p> <p>We examined informed consent (IC) forms from 30 cancer genome sequencing studies to assess (1) stated purpose of sample collection, (2) scope of consent requested, (3) data sharing protocols (4) privacy protection measures, (5) described risks of participation, (6) subject re-contacting, and (7) protocol for withdrawal.</p> <p>Results</p> <p>There is a high degree of similarity in how cancer researchers engaged in WGS are protecting participant privacy. We observed a strong trend towards both using samples for additional, unspecified research and sharing data with other investigators. IC forms were varied in terms of how they discussed re-contacting participants, returning results and facilitating participant withdrawal. Contrary to expectation, there were no consistent trends that emerged over the eight year period from which forms were collected.</p> <p>Conclusion</p> <p>Examining IC forms from WGS studies elucidates how investigators are handling ELS challenges posed by this research. This information is important for ensuring that while the public benefits of research are maximized, the rights of participants are also being appropriately respected.</p

Effects of iron-ore mining and processing on metal bioavailability in a tropical coastal lagoon

In water systems, water quality and geochemical properties of sediments determine the speciation of trace metals, metal transport, and sediment-water exchange, influencing metal availability and its potential effects on biota. Studies from temperate climates have shown that iron-ore mining and tailing wastewaters, besides being a source of trace metals, usually show high levels of dissolved ions and particulate suspended matter, thus having the potential of indirectly changing metal bioavailability. For the first time in the tropics, we identified the effects of iron-ore mining and processing on metal bioavailability in a coastal lagoon. With an extensive sampling scheme, we investigated the potential sources of metals; the links among metal levels in water, sediments, and invertebrates; and the contrasting effects on metal speciation and bioavailability. The metals Fe, Mn, Al, Cr, Zn, Cu, Ni, Pb, Cd, Hg, and As were measured in water, sediments (surface and profiles), and invertebrates from Mãe-Bá Lagoon and in the sites directly influenced by the mining operations (tailing dams and nearby rivers). In addition, samples from two other lagoons, considered pristine, were analyzed. The study area is located in the southeast of Brazil (Iron Quadrangle Region and a coastal area of Espírito Santo State). General water characteristics included pH, dissolved organic carbon, alkalinity, and anion composition. Water metal speciation was assessed by a speciation model (Chemical Equilibria in Aquatic Systems). Grain-size distribution, organic carbon, carbonate, and acid volatile sulfide (AVS) were determined in sediments. Statistical methods included comparison of means by Mann-Whitney test, ordination and correlation analyses, and analysis of regression for geochemical normalization of metals with grain size. The dissolved metal concentrations, the total metal levels in sediments, and the normalization based on the fine sediment fraction showed that the mining operations constitute potential sources of Fe, Mn, Cr, Cu, Ni, Pb, As, and Hg to Mãe-Bá Lagoon. However, trace metal availability was reduced because of increased pH, hardness, and sulfide content (356 μmol/g) in the sites influenced by the mining. The lagoon showed similar water chemistry as in the mining sites, with metal bioavailability further decreased by the presence of dissolved organic carbon and chloride. Although AVS levels in the lagoon were low (0.48-56 μmol/g), metal bioavailability was reduced because of the presence of organic matter. Metal levels in invertebrates confirmed the predicted low metal bioavailability in Mãe-Bá Lagoon. The lagoon was considered moderately contaminated only by Hg and As. The iron-ore mining and processing studied here constitute potential sources of metal pollution into the tropical lagoon. Contrary to expectations, however, it also contributes to reducing the overall metal bioavailability in the lagoon. These findings are believed to be useful for evaluating metal exposure in a more integrated way, identifying not only the sources of pollution but also how they can affect the components involved in metal speciation and bioavailability in water systems, leading to new insights

Trace Elements and Carbon and Nitrogen Stable Isotopes in Organisms from a Tropical Coastal Lagoon

Trace elements (Fe, Mn, Al, Zn, Cr, Cu, Ni, Pb, Cd, Hg, and As) and stable isotope ratios (δ13C and δ15N) were analyzed in sediments, invertebrates, and fishes from a tropical coastal lagoon influenced by iron ore mining and processing activities to assess the differences in trace element accumulation patterns among species and to investigate relations with trophic levels of the organisms involved. Overall significant negative relations between trophic level (given by 15N) and trace element concentrations in gastropods and crustaceans showed differences in internal controls of trace element accumulation among the species of different trophic positions, leading to trace element dilution. Generally, no significant relation between δ15N and trace element concentrations was observed among fish species, probably due to omnivory in a number of species as well as fast growth. Trace element accumulation was observed in the fish tissues, with higher levels of most trace elements found in liver compared with muscle and gill. Levels of Fe, Mn, Al, and Hg in invertebrates, and Fe and Cu in fish livers, were comparable with levels in organisms and tissues from other contaminated areas. Trace element levels in fish muscle were below the international safety baseline standards for human consumption

Precision medicine driven by cancer systems biology

Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Land-sea interface features of four estuaries on the South America Atlantic coast

The Brazilian coastal zone extends from 4º N to 34º S latitude and because of its long extension, the interface zone from continent to ocean includes a high diversity of geomorphologic and oceanographic characteristics. The rivers from the Northeast and East regions are marked by a typical unimodal seasonal flux patterns but with different amplitudes. As the climate indicates, the rivers from the Northeast are subject to an accentuated seasonal variability with an elevated input and flood pulses during the rainy season and low to negligible fluxes during the dry season. Small-scale rivers usually present typical torrential behaviour. In the humid eastern region, the unimodal seasonal cycle is dampened with a more constant input supply. Recently, some studies have shown that the material supply from rivers along the Northeast and Eastern coasts is diluted by surface tropical waters of oceanic currents and that the estuarine plume dispersal is restricted to a narrow coastal belt. However, human impacts of course mask or even override both natural hydrological cycles and CO2 emissions from terrestrial biomes, or depending on the nature of the human impact, can even increase extreme events. Henceforth this contribution addresses the typological, hydrological and biome diversity of the four estuarine systems fed and affected by the respective Amazon, São Francisco, Paraíba do Sul and Plata watersheds