Land-use intensification differentially affects bacterial, fungal and protist communities and decreases microbiome network complexity

Background: Soil microbial communities are major drivers of cycling of soil nutrients that sustain plant growth and productivity. Yet, a holistic understanding of the impact of land-use intensification on the soil microbiome is still poorly understood. Here, we used a field experiment to investigate the long-term consequences of changes in land-use intensity based on cropping frequency (continuous cropping, alternating cropping with a temporary grassland, perennial grassland) on bacterial, protist and fungal communities as well as on their co-occurrence networks. Results: We showed that land use has a major impact on the structure and composition of bacterial, protist and fungal communities. Grassland and arable cropping differed markedly with many taxa differentiating between both land use types. The smallest differences in the microbiome were observed between temporary grassland and continuous cropping, which suggests lasting effects of the cropping system preceding the temporary grasslands. Land-use intensity also affected the bacterial co-occurrence networks with increased complexity in the perennial grassland comparing to the other land-use systems. Similarly, co-occurrence networks within microbial groups showed a higher connectivity in the perennial grasslands. Protists, particularly Rhizaria, dominated in soil microbial associations, as they showed a higher number of connections than bacteria and fungi in all land uses. Conclusions: Our findings provide evidence of legacy effects of prior land use on the composition of the soil microbiome. Whatever the land use, network analyses highlighted the importance of protists as a key element of the soil microbiome that should be considered in future work. Altogether, this work provides a holistic perspective of the differential responses of various microbial groups and of their associations to agricultural intensification

The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort.

PURPOSE: It has been argued that rare diseases should be recognized as a public health priority. However, there is a shortage of epidemiological data describing the true burden of rare diseases. This study investigated hospital service use to provide a better understanding of the collective health and economic impacts of rare diseases. METHODS: Novel methodology was developed using a carefully constructed set of diagnostic codes, a selection of rare disease cohorts from hospital administrative data, and advanced data-linkage technologies. Outcomes included health-service use and hospital admission costs. RESULTS: In 2010, cohort members who were alive represented approximately 2.0% of the Western Australian population. The cohort accounted for 4.6% of people discharged from hospital and 9.9% of hospital discharges, and it had a greater average length of stay than the general population. The total cost of hospital discharges for the cohort represented 10.5% of 2010 state inpatient hospital costs. CONCLUSIONS: This population-based cohort study provides strong new evidence of a marked disparity between the proportion of the population with rare diseases and their combined health-system costs. The methodology will inform future rare-disease studies, and the evidence will guide government strategies for managing the service needs of people living with rare diseases.Genet Med advance online publication 22 September 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.143

Patient organization involvement and the challenge of securing access to treatments for rare diseases:Report of a policy engagement workshop

Plain English summary Patients with rare diseases often help to develop new treatments for their conditions. But once developed, those treatments are sometimes priced too high for many patients to access them. We became aware that this is a problem in the course of a social science research project that examines the place of rare diseases in health policy. We therefore organized a two-day workshop to try and understand why this problem occurs and what might be done about it. The people who participated in our workshop were: representatives of rare disease patient organizations, experts in matters of drug regulation and assessment of new health technologies, consultants involved with companies producing treatments for rare diseases, and social scientists researching related issues. The main conclusions to emerge from the discussions were as follows: Problems of access to treatments for rare diseases are not just due to high prices; procedures for regulating, assessing and delivering new treatments also need to be better organized. Patients and patient organizations have much to contribute to this process. However, their resources are often very limited. Consequently, more needs to be done to help them use those resources as effectively as possible. In particular, regulators and healthcare providers need to ensure that their procedures are clear and efficiently managed, so as not to waste patient organizations’ time and money. Clearer guidance is needed on what patient organizations can do to provide evidence of the effectiveness of new drugs. Insights gained in tackling rare diseases might also be applicable to common disorders. Finally, the consequences of Brexit for UK policies on rare diseases urgently need to be assessed. Abstract Since the enactment of orphan drug legislation in the USA, Europe and several other countries, an increasing number of treatments for rare diseases have been developed and many of them been approved for marketing. However, such treatments tend to be priced very high, and access to effective treatments remains a major challenge for patients with rare diseases – despite active involvement of patients and their support organizations in various stages of basic and applied research and commercial development. In order to allow patients to benefit from treatments proved effective for their diseases, we need to better understand why this challenge persists, and what steps might be taken to address it. To that end, we organized a policy-engagement workshop, bringing together individuals and organizations with direct experience of trying to secure access to a treatment for a rare disease along with individuals with relevant expertise in regulatory and commissioning processes for new medicines. With additional input from social scientists who offered different perspectives on the value of patient involvement, the workshop aimed to initiate a dialogue among the participants about how to address the challenge in a sustainable manner. Discussions at the workshop stressed that active involvement of patients is as valuable in the regulatory and commissioning processes as in the research and development of new medicines. However, it also highlighted certain risks and costs associated with such involvement. These include the costs of adjusting to abrupt changes in regulatory and commissioning processes, and the risk of being perceived as too close to commercial interests. To optimize use of scarce resources and ensure continuing active involvement, such risks and costs need to be better managed. Participants also noted that, owing to advances in genomic technologies, common diseases are also becoming divided into rare sub-categories, which are equally eligible for orphan drug designation. Consequently, involvement of wider patient communities beyond rare disease communities will be critical for continuing discussions about patients’ involvement in regulatory and commissioning processes, and to consider how patients and their support organizations can best work with other stakeholders – including companies, regulators and policymakers – to ensure access to effective medicines

Evolving cohesion metrics of a research network on rare diseases: a longitudinal study over 14 years

[EN] Research collaboration is necessary, rewarding, and beneficial. Cohesion between team members is related to their collective efficiency. To assess collaboration processes and their eventual outcomes, agencies need innovative methods-and social network approaches are emerging as a useful analytical tool. We identified the research output and citation data of a network of 61 research groups formally engaged in publishing rare disease research between 2000 and 2013. We drew the collaboration networks for each year and computed the global and local measures throughout the period. Although global network measures remained steady over the whole period, the local and subgroup metrics revealed a growing cohesion between the teams. Transitivity and density showed little or no variation throughout the period. In contrast the following points indicated an evolution towards greater network cohesion: the emergence of a giant component (which grew from just 30 % to reach 85 % of groups); the decreasing number of communities (following a tripling in the average number of members); the growing number of fully connected subgroups; and increasing average strength. Moreover, assortativity measures reveal that, after an initial period where subject affinity and a common geographical location played some role in favouring the connection between groups, the collaboration was driven in the final stages by other factors and complementarities. The Spanish research network on rare diseases has evolved towards a growing cohesion-as revealed by local and subgroup metrics following social network analysis.The Spanish Ministry of Economics and Competitiveness partially supported this research (Grant Number ECO2014-59381-R).Benito Amat, C.; Perruchas, F. (2016). Evolving cohesion metrics of a research network on rare diseases: a longitudinal study over 14 years. Scientometrics. 108(1):41-56. https://doi.org/10.1007/s11192-016-1952-zS41561081Aymé, S., & Schmidtke, J. (2007). Networking for rare diseases: A necessity for Europe. Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 50(12), 1477–1483. doi: 10.1007/s00103-007-0381-9 .Barabási, A. L., Jeong, H., Néda, Z., Ravasz, E., Schubert, A., & Vicsek, T. (2002). Evolution of the social network of scientific collaborations. Physica A: Statistical Mechanics and its Applications, 311(3–4), 590–614. doi: 10.1016/S0378-4371(02)00736-7 .Bettencourt, L. M. A., Kaiser, D. I., & Kaur, J. (2009). Scientific discovery and topological transitions in collaboration networks. Journal of Informetrics, 3(3), 210–221. doi: 10.1016/j.joi.2009.03.001 .Bian, J., Xie, M., Topaloglu, U., Hudson, T., Eswaran, H., & Hogan, W. (2014). Social network analysis of biomedical research collaboration networks in a CTSA institution. Journal of Biomedical Informatics, 52, 130–140. doi: 10.1016/j.jbi.2014.01.015 .Bordons, M., Aparicio, J., González-Albo, B., & Díaz-Faes, A. A. (2015). The relationship between the research performance of scientists and their position in co-authorship networks in three fields. Journal of Informetrics, 9(1), 135–144. doi: 10.1016/j.joi.2014.12.001 .Börner, K., Dall’Asta, L., Ke, W., & Vespignani, A. (2005). Studying the emerging global brain: Analyzing and visualizing the impact of co-authorship teams. Complexity, 10(4), 57–67. doi: 10.1002/cplx.20078 .Casey-Campbell, M., & Martens, M. L. (2009). Sticking it all together: A critical assessment of the group cohesion–performance literature. International Journal of Management Reviews, 11(2), 223–246. doi: 10.1111/j.1468-2370.2008.00239.x .Chiocchio, F., & Essiembre, H. (2009). Cohesion and performance: A meta-analytic review of disparities between project teams, Production teams, and service teams. Small group research, 40(4), 382–420. doi: 10.1177/1046496409335103 .Cho, A. (2011). Particle physicists’ new extreme teams. Science, 333(6049), 1564–1567. doi: 10.1126/science.333.6049.1564 .Cooke, N. J., & Hilton, M. L. (2015). Enhancing the effectiveness of team science. Washington, D.C.: National Academies Press. Recuperado a partir de http://www.nap.edu/catalog/19007/enhancing-the-effectiveness-of-team-science .Cugmas, M., Ferligoj, A., & Kronegger, L. (2015). The stability of co-authorship structures. Scientometrics, 106(1), 163–186. doi: 10.1007/s11192-015-1790-4 .Estrada, E. (2011). The structure of complex networks: Theory and applications. Oxford: University Press.Gallivan, M., & Ahuja, M. (2015). Co-authorship, homophily, and scholarly influence in information systems research. Journal of the Association for Information Systems, 16(12), 980.Ghosh, J., Kshitij, A., & Kadyan, S. (2014). Functional information characteristics of large-scale research collaboration: Network measures and implications. Scientometrics, 102(2), 1207–1239. doi: 10.1007/s11192-014-1475-4 .Heymann, S. (2014). Gephi. In R. Alhajj & J. Rokne (Eds.), Encyclopedia of social network analysis and mining (pp. 612–625). New York: Springer.Himmelstein, D. S., & Powell, K. (2016). Analysis for “the history of publishing delays” blog post v1.0. Zenodo,. doi: 10.5281/zenodo.45516 .Hunt, J. D., Whipple, E. C., & McGowan, J. J. (2012). Use of social network analysis tools to validate a resources infrastructure for interinstitutional translational research: A case study. Journal of the Medical Library Association, 100(1), 48–54. doi: 10.3163/1536-5050.100.1.009 .Kolaczyk, E. D., & Csardi, G. (2014). Statistical analysis of network data with R (Vol. 65). New York: Springer.Kumar, S. (2015). Efficacy of a giant component in co-authorship networks: Evidence from a Southeast Asian dataset in economics. Aslib Journal of Information Management, 68(1), 19–32. doi: 10.1108/AJIM-12-2014-0172 .Larivière, V., Gingras, Y., Sugimoto, C. R., & Tsou, A. (2015). Team size matters: Collaboration and scientific impact since 1900. Journal of the Association for Information Science and Technology, 66(7), 1323–1332. doi: 10.1002/asi.23266 .Laudel, G. (2002). What do we measure by co-authorships? Research Evaluation, 11(1), 3–15. doi: 10.3152/147154402781776961 .Liu, X., Bollen, J., Nelson, M. L., & Van de Sompel, H. (2005). Co-authorship networks in the digital library research community. Information Processing and Management, 41(6), 1462–1480. doi: 10.1016/j.ipm.2005.03.012 .Liu, P., & Xia, H. (2015). Structure and evolution of co-authorship network in an interdisciplinary research field. Scientometrics, 103(1), 101–134. doi: 10.1007/s11192-014-1525-y .Ministerio de Sanidad y Consumo. Resolución de 30 de marzo de. (2006) del Instituto de Salud Carlos III, por la que se convocan ayudas destinadas a financiar estructuras estables de investigación cooperativa, en el área de biomedicina y ciencias de la salud, en el marco de la iniciativa Ingenio 2010, programa Consolider, acciones CIBER, 83 Boletín Oficial del Estado (pp. 13770–13777).Newman, M. E. J. (2001a). Scientific collaboration networks. II. Shortest paths, weighted networks, and centrality. Physical Review E, 64(1), 016132. doi: 10.1103/PhysRevE.64.016132 .Newman, M. E. J. (2001b). Scientific collaboration networks. I. Network construction and fundamental results. Physical Review E, 64(1), 016131. doi: 10.1103/PhysRevE.64.016131 .Newman, M. E. J. (2003a). Mixing patterns in networks. Physical Review E, 67(2), 026126. doi: 10.1103/PhysRevE.67.026126 .Newman, M. E. J. (2003b). The structure and function of complex networks. SIAM Review, 45, 167–256.OECD. (2010). Measuring innovation: A new perspective. Paris: OCDE Publishing.Ramasco, J., & Morris, S. (2006). Social inertia in collaboration networks. Physical Review E, 73(1), 016122. doi: 10.1103/PhysRevE.73.016122 .Sonnenwald, D. H. (2007). Scientific collaboration. Annual Review of Information Science and Technology, 41(1), 643–681. doi: 10.1002/aris.2007.1440410121 .Wuchty, S., Jones, B. F., & Uzzi, B. (2007). The increasing dominance of teams in production of knowledge. Science, 316(5827), 1036–1039. doi: 10.1126/science.1136099

Patient/family views on data sharing in rare diseases: study in the European LeukoTreat project.: Survey assessing data sharing in leukodystrophies

International audienceThe purpose of this study was to explore patient and family views on the sharing of their medical data in the context of compiling a European leukodystrophies database. A survey questionnaire was delivered with help from referral centers and the European Leukodystrophies Association, and the questionnaires returned were both quantitatively and qualitatively analyzed. This study found that patients/families were strongly in favor of participating. Patients/families hold great hope and trust in the development of this type of research. They have a strong need for information and transparency on database governance, the conditions framing access to data, all research conducted, partnerships with the pharmaceutical industry, and they also need access to results. Our findings bring ethics-driven arguments for a process combining initial broad consent with ongoing information. On both, we propose key item-deliverables to database participants

Evaluación en campo de plantas regeneradas por embriogénesis somática a partir de ápices de brotes de yemas axilares en cv. ‘Navolean’ (Musa spp., AAB)

The use of shoots apexes from axilary buds for callus induction with embryogenic structures in plantain ‘Navolean’ (Group AAB) permitted to develop a plant regeneration method through out somatic embryogenesis. In order to know the phenotypic variants that may be produced with the previously mentioned method , 1000 plants were planted in field conditions in comparison to those coming from somatic embryos obtained from multibuds as initial explants and organogenesis-derived plants (shoot tips)and conventionally derived plants (corms), during two growing cycles. The main morphological characters and yield components were evaluated. The total frequency of somaclonal variation during the first growing cycle in plants coming from somatic embryos obtained from shoots apexes from axilary buds as initial explants were 1.1%, and 8,6% in regenerated plants from somatic embryos obtained from multi-buds as initial explants. Later, in this same growing cycle, plants regenerated from somatic embryos (both sources) showed a similar performance between them and they were significantly superior in all evaluated variants in comparison to corm-derived plants. In the second growing cycle, significant differences were not observed in yield components of suckers from evaluated plants, in spite of the propagation method used. With regard to somaclonal variation, the best performance was obtained with shoots apexes from axilary buds as explants. Finally, the feasibility of using the new method was shown.Key words: embryogenic cell suspensions, somaclonal variationEl uso de ápices de brotes de yemas axilares para la inducción de callos con estructuras embriogénicas en el cultivar de plátano vianda ‘Navolean’ (Grupo AAB), posibilitó el desarrollo de una metodología de regeneración de plantas por embriogénesis somática en el cultivar objeto de estudio. Con el objetivo de conocer la variabilidad fenotípica que se podría producir mediante la misma, se plantaron en el campo 1 000 plantas que se compararon durante dos ciclos de cultivo con otras procedentes de embriones somáticos obtenidos de scalps de multiyemas como explante inicial, con plantas obtenidas por organogénesis (ápices meristemáticos) y mediante la propagación convencional (cormos). Para ello se evaluaron los principales caracteres morfológicos de la planta y componentes del rendimiento.La frecuencia total de variación somaclonal durante el primer ciclo de cultivo en las plantas procedentes de embriones somáticos donde el explante inicial habían sido ápices de brotes de yemas axilares fue de 1.1% y de 8.6% en las plantas regeneradas de embriones somáticos scalps de multiyemas. Luego en este mismo ciclo de cultivo las plantas regeneradas de embriones somáticos (ambas procedencias) mostraron un comportamiento similar entre ellas y en todas las variables evaluadas fueron superiores en relación con las plantas procedentes de cormos con diferencias significativas. En el segundo ciclo de cultivo, al evaluar los hijos, de las plantas estudiadas no se observaron diferencias significativas en los componentes del rendimiento, independientemente del método de propagación utilizado. Referente a la variación somaclonal, se obtuvo el menor índice en las plantas obtenidas por embriogénesis a partir de ápices de yemas axilares. Finalmente se demostró la factibilidad de utilizar la nueva metodología desarrollada.Palabras clave: suspensiones celulares embriogénicas, variación somaclona

Lab to Field Assessment of the Ecotoxicological Impact of Chlorpyrifos, Isoproturon, or Tebuconazole on the Diversity and Composition of the Soil Bacterial Community

Pesticides are intentionally applied to agricultural fields for crop protection. They can harm non-target organisms such as soil microorganisms involved in important ecosystem functions with impacts at the global scale. Within the frame of the pesticide registration process, the ecotoxicological impact of pesticides on soil microorganisms is still based on carbon and nitrogen mineralization tests, despite the availability of more extensive approaches analyzing the abundance, activity or diversity of soil microorganisms. In this study, we used a high-density DNA microarray (PhyloChip) and 16S rDNA amplicon next-generation sequencing (NGS) to analyze the impact of the organophosphate insecticide chlorpyrifos (CHL), the phenyl-urea herbicide isoproturon (IPU), or the triazole fungicide tebuconazole (TCZ) on the diversity and composition of the soil bacterial community. To our knowledge, it is the first time that the combination of these approaches are applied to assess the impact of these three pesticides in a lab-to-field experimental design. The PhyloChip analysis revealed that although no significant changes in the composition of the bacterial community were observed in soil microcosms exposed to the pesticides, significant differences in detected operational taxonomic units (OTUs) were observed in the field experiment between pesticide treatments and control for all three tested pesticides after 70 days of exposure. NGS revealed that the bacterial diversity and composition varied over time. This trend was more marked in the microcosm than in the field study. Only slight but significant transient effects of CHL or TCZ were observed in the microcosm and the field study, respectively. IPU was not found to significantly modify the soil bacterial diversity or composition. Our results are in accordance with conclusions of the Environmental Food Safety Authority (EFSA), which concluded that these three pesticides may have a low risk toward soil microorganisms

Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised