1. |
- Mercuri, E., et al.
(author)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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In: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Journal article (peer-reviewed)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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2. |
- Ralimanana, H., et al.
(author)
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Madagascar’s extraordinary biodiversity: Threats and opportunities
- 2022
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6623
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Research review (peer-reviewed)abstract
- Madagascar’s unique biota is heavily affected by human activity and is under intense threat. Here, we review the current state of knowledge on the conservation status of Madagascar’s terrestrial and freshwater biodiversity by presenting data and analyses on documented and predicted species-level conservation statuses, the most prevalent and relevant threats, ex situ collections and programs, and the coverage and comprehensiveness of protected areas. The existing terrestrial protected area network in Madagascar covers 10.4% of its land area and includes at least part of the range of the majority of described native species of vertebrates with known distributions (97.1% of freshwater fishes, amphibians, reptiles, birds, and mammals combined) and plants (67.7%). The overall figures are higher for threatened species (97.7% of threatened vertebrates and 79.6% of threatened plants occurring within at least one protected area). International Union for Conservation of Nature (IUCN) Red List assessments and Bayesian neural network analyses for plants identify overexploitation of biological resources and unsustainable agriculture as the most prominent threats to biodiversity. We highlight five opportunities for action at multiple levels to ensure that conservation and ecological restoration objectives, programs, and activities take account of complex underlying and interacting factors and produce tangible benefits for the biodiversity and people of Madagascar.
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4. |
- Antonelli, Alexandre, 1978, et al.
(author)
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Madagascar's extraordinary biodiversity : Evolution, distribution, and use
- 2022
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6623, s. 962-
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Journal article (peer-reviewed)abstract
- Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique " living laboratory" for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity.
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5. |
- Ulian, T., et al.
(author)
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Unlocking plant resources to support food security and promote sustainable agriculture
- 2020
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In: Plants People Planet. - : Wiley. - 2572-2611. ; 2:5, s. 421-445
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Journal article (peer-reviewed)abstract
- Societal Impact Statement Biodiversity is essential to food security and nutrition locally and globally. By reviewing the global state of edible plants and highlighting key neglected and underutilized species (NUS), we attempt to unlock plant food resources and explore the role of fungi, which along with the wealth of traditional knowledge about their uses and practices, could help support sustainable agriculture while ensuring better protection of the environment and the continued delivery of its ecosystem services. This work will inform a wide range of user communities, including scientists, conservation and development organizations, policymakers, and the public of the importance of biodiversity beyond mainstream crops. Summary As the world's population is increasing, humanity is facing both shortages (hunger) and excesses (obesity) of calorie and nutrient intakes. Biodiversity is fundamental to addressing this double challenge, which involves a far better understanding of the global state of food resources. Current estimates suggest that there are at least 7,039 edible plant species, in a broad taxonomic sense, which includes 7,014 vascular plants. This is in striking contrast to the small handful of food crops that provide the majority of humanity's calorie and nutrient intake. Most of these 7,039 edible species have additional uses, the most common being medicines (70%), materials (59%), and environmental uses (40%). Species of major food crops display centers of diversity, as previously proposed, while the rest of edible plants follow latitudinal distribution patterns similarly to the total plant diversity, with higher species richness at lower latitudes. The International Union for Conservation of Nature Red List includes global conservation assessments for at least 30% of edible plants, with ca. 86% of them conserved ex situ. However, at least 11% of those species recorded are threatened. We highlight multipurpose NUS of plants from different regions of the world, which could be key for a more resilient, sustainable, biodiverse, and community participation-driven new "green revolution." Furthermore, we explore how fungi could diversify and increase the nutritional value of our diets. NUS, along with the wealth of traditional knowledge about their uses and practices, offer a largely untapped resource to support food security and sustainable agriculture. However, for these natural resources to be unlocked, enhanced collaboration among stakeholders is vital.
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6. |
- Pironon, S., et al.
(author)
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Toward Unifying Global Hotspots of Wild and Domesticated Biodiversity
- 2020
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In: Plants. - : MDPI AG. - 2223-7747. ; 9:9
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Journal article (peer-reviewed)abstract
- Global biodiversity hotspots are areas containing high levels of species richness, endemism and threat. Similarly, regions of agriculturally relevant diversity have been identified where many domesticated plants and animals originated, and co-occurred with their wild ancestors and relatives. The agro-biodiversity in these regions has, likewise, often been considered threatened. Biodiversity and agro-biodiversity hotspots partly overlap, but their geographic intricacies have rarely been investigated together. Here we review the history of these two concepts and explore their geographic relationship by analysing global distribution and human use data for all plants, and for major crops and associated wild relatives. We highlight a geographic continuum between agro-biodiversity hotspots that contain high richness in species that are intensively used and well known by humanity (i.e., major crops and most viewed species on Wikipedia) and biodiversity hotspots encompassing species that are less heavily used and documented (i.e., crop wild relatives and species lacking information on Wikipedia). Our contribution highlights the key considerations needed for further developing a unifying concept of agro-biodiversity hotspots that encompasses multiple facets of diversity (including genetic and phylogenetic) and the linkage with overall biodiversity. This integration will ultimately enhance our understanding of the geography of human-plant interactions and help guide the preservation of nature and its contributions to people.
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7. |
- Freud, Lindsay R., et al.
(author)
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Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age
- 2024
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In: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 230:3
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Journal article (peer-reviewed)abstract
- Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. Study Design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. Results: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56–11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69–0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06–0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03–0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36–0.91; P=.019). Conclusion: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.
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8. |
- Gorasso, Vanessa, et al.
(author)
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Burden of disease attributable to risk factors in European countries: a scoping literature review
- 2023
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In: Archives of Public Health. - 0778-7367 .- 2049-3258. ; 81:1
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Research review (peer-reviewed)abstract
- Objectives: Within the framework of the burden of disease (BoD) approach, disease and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe; and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. Methods: We searched multiple literature databases, including grey literature websites and targeted public health agencies websites. Results: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors, since they might significantly influence the quantification of the attributable burden. From our analysis we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. Conclusions: Our review also highlighted misreporting, the lack of uncertainty analysis and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, avoid misinterpretations thus improving comparability among estimates.
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10. |
- Herrera-Luis, E, et al.
(author)
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Admixture mapping of severe asthma exacerbations in Hispanic/Latino children and youth
- 2023
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In: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 78:3, s. 233-241
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Journal article (peer-reviewed)abstract
- In the USA, genetically admixed populations have the highest asthma prevalence and severe asthma exacerbations rates. This could be explained not only by environmental factors but also by genetic variants that exert ethnic-specific effects. However, no admixture mapping has been performed for severe asthma exacerbations.ObjectiveWe sought to identify genetic variants associated with severe asthma exacerbations in Hispanic/Latino subgroups by means of admixture mapping analyses and fine mapping, and to assess their transferability to other populations and potential functional roles.MethodsWe performed an admixture mapping in 1124 Puerto Rican and 625 Mexican American children with asthma. Fine-mapping of the significant peaks was performed via allelic testing of common and rare variants. We performed replication across Hispanic/Latino subgroups, and the transferability to non-Hispanic/Latino populations was assessed in 1001 African Americans, 1250 Singaporeans and 941 Europeans with asthma. The effects of the variants on gene expression and DNA methylation from whole blood were also evaluated in participants with asthma and in silico with data obtained through public databases.ResultsGenomewide significant associations of Indigenous American ancestry with severe asthma exacerbations were found at 5q32 in Mexican Americans as well as at 13q13-q13.2 and 3p13 in Puerto Ricans. The single nucleotide polymorphism (SNP) rs1144986 (C5orf46) showed consistent effects for severe asthma exacerbations across Hispanic/Latino subgroups, but it was not validated in non-Hispanics/Latinos. This SNP was associated withDPYSL3DNA methylation andSCGB3A2gene expression levels.ConclusionsAdmixture mapping study of asthma exacerbations revealed a novel locus that exhibited Hispanic/Latino-specific effects and regulatedDPYSL3andSCGB3A2.
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11. |
- Cowell, C., et al.
(author)
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Uses and benefits of digital sequence information from plant genetic resources: Lessons learnt from botanical collections
- 2022
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In: Plants People Planet. - : Wiley. - 2572-2611. ; 4:1, s. 33-43
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Journal article (peer-reviewed)abstract
- Societal Impact Statement Digitized molecular data are vital to numerous aspects of scientific research and genetic resource use. The Convention on Biological Diversity currently refers to this as "Digital Sequence Information" (DSI), a term not widely adopted by science and lacking a clear definition. There are concerns over the access to genetic resources and absence of benefit sharing by provider countries. Open access to DSI might exacerbate this, which is leading to increasing policy interventions and restricted access to genetic resources and DSI. We analyze current international debate and proposed solutions and provide case studies of DSI use producing tangible benefits for the provider countries and scientific research, demonstrating the importance of open access DSI to achieving conservation goals. Substantial advances in DNA sequencing over the last decades hold great potential to enhance food security and sustainable use of global biodiversity, benefiting the world's poorest people. Digital Sequence Information (DSI) plays a crucial role in catalyzing research applications that can contribute to international societal and biodiversity conservation targets. However, benefit sharing relating to DSI is difficult to identify and hindered by the lack of clear international governance and legislation, which in turn has led to a reluctance to make DSI publicly and freely available. Critically, no precise definition exists under the Convention on Biological Diversity (CBD), the Nagoya Protocol (NP), or the International Treaty for Plant Genetic Resources for Food and Agriculture (ITPGRFA). The key difference between DSI and biological resources, for which access and use are highly regulated under those frameworks, is that information is nonphysical. Information can be replicated and used without movement of, or access to, physical specimens. Thus, regulating the use of DSI is extremely challenging and remains controversial. Here, we review the regulation of DSI and the possible future steps by the international community, in the context of the benefit-sharing obligations of the CBD, NP, and ITPGRFA. We highlight how multilateral agreements work in practice and are a solution to this impasse. We provide case studies demonstrating how the Royal Botanic Gardens, Kew, and its collaborators address the uncertainty surrounding the use of DSI, illustrating tangible and equitable benefits that have arisen from such use. We conclude that open access to DSI is needed for scientific research and international policy.
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12. |
- Rocklöv, Joacim, Professor, 1979-, et al.
(author)
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Decision-support tools to build climate resilience against emerging infectious diseases in Europe and beyond
- 2023
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In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 32
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Research review (peer-reviewed)abstract
- Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains at the animal, human, and environmental interface. This entails the co-development of early warning and response systems and tools to assess the costs and benefits of climate change adaptation and mitigation measures across sectors, to increase health system resilience at regional and local levels and reveal novel policy entry points and opportunities. Our approach involves multi-level engagement, innovative methodologies, and novel data streams. We take advantage of intelligence generated locally and empirically to quantify effects in areas experiencing rapid urban transformation and heterogeneous climate-induced disease threats. Our goal is to reduce the knowledge-to-action gap by developing an integrated One Health—Climate Risk framework.
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