| 1. |
- Heslop, James A., et al.
(author)
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Concise Review : Workshop Review: Understanding and Assessing the Risks of Stem Cell-Based Therapies
- 2015
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In: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:4, s. 389-400
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Research review (peer-reviewed)abstract
- The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting-edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.
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| 2. |
- Testor, Pierre, et al.
(author)
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OceanGliders: A component of the integrated GOOS
- 2019
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Research review (peer-reviewed)abstract
- The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintian and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.
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| 3. |
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| 4. |
- Bladen, Catherine L., et al.
(author)
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The TREAT-NMD Duchenne Muscular Dystrophy Registries : Conception, Design, and Utilization by Industry and Academia
- 2013
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 34:11, s. 1449-1457
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Journal article (peer-reviewed)abstract
- Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence<5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.
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| 5. |
- Kia, Richard, et al.
(author)
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MicroRNA-122 : a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity
- 2015
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In: Toxicological Sciences. - : Oxford University Press. - 1096-6080 .- 1096-0929. ; 144:1, s. 173-185
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Journal article (peer-reviewed)abstract
- Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated cells is currently lacking, as the cytotoxicity assays routinely used in in vitro toxicology research depend on intracellular molecules which are ubiquitously present in all eukaryotic cell types. In this study, we demonstrate that microRNA-122 (miR-122) detection in cell culture media can be used as a hepatocyte-enriched in vitro marker of drug-induced toxicity in homogeneous cultures of hepatic cells, and a cell-specific marker of toxicity of hepatic cells in heterogeneous cultures such as HLCs generated from various differentiation protocols and pluripotent stem cell lines, where conventional cytotoxicity assays using generic cellular markers may not be appropriate. We show that the sensitivity of the miR-122 cytotoxicity assay is similar to conventional assays that measure lactate dehydrogenase activity and intracellular adenosine triphosphate when applied in hepatic models with high levels of intracellular miR-122, and can be multiplexed with other assays. MiR-122 as a biomarker also has the potential to bridge results in in vitro experiments to in vivo animal models and human samples using the same assay, and to link findings from clinical studies in determining the relevance of in vitro models being developed for the study of drug-induced liver injury.
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| 6. |
- Larsen, Kasper J.
(author)
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Maximal Unitarity at Two Loops : A New Method for Computing Two-Loop Scattering Amplitudes
- 2012
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Doctoral thesis (other academic/artistic)abstract
- The study of scattering amplitudes beyond one loop is necessary for precision phenomenology for the Large Hadron Collider and may also provide deeper insights into the theoretical foundations of quantum field theory. In this thesis we develop a new method for computing two-loop amplitudes, based on unitarity rather than Feynman diagrams. In this approach, the two-loop amplitude is first expanded in a linearly independent basis of integrals. The process dependence thereby resides in the coefficients of the integrals. These expansion coefficients are then the object of calculation.Our main results include explicit formulas for a subset of the integral coefficients, expressing them as products of tree-level amplitudes integrated over specific contours in the complex plane. We give a general selection principle for determining these contours. This principle is then applied to obtain the coefficients of integrals with the topology of a double box. We show that, for four-particle scattering, each double-box integral in the two-loop basis is associated with a uniquely defined complex contour, referred to as its master contour. We provide a classification of the solutions to setting all propagators of the general double-box integral on-shell. Depending on the number of external momenta at the vertices of the graph, these solutions are given as a chain of pointwise intersecting Riemann spheres, or a torus. This classification is needed to define master contours for amplitudes with arbitrary multiplicities.We point out that a basis of two-loop integrals with as many infrared finite elements as possible allows substantial technical simplications, in terms of obtaining the coefficients of the integrals, as well as for the analytic evaluation of the integrals themselves. We compute two such integrals at four points, obtaining remarkably compact expressions. Finally, we provide a check on a recently developed recursion relation for the all-loop integrand of the amplitudes of N=4 supersymmetric Yang-Mills theory, examining the two-loop six-gluon MHV amplitude and finding agreement. The validity of the approach to two-loop amplitudes developed in this thesis extends to all four-dimensional gauge theories, in particular QCD. The approach is suited for obtaining compact analytical expressions as well as for numerical implementations.
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| 7. |
- Rauch, Sebastien, 1971, et al.
(author)
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Anthropogenic Forcings on the Surficial Osmium Cycle
- 2010
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:3, s. 881-887
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Journal article (peer-reviewed)abstract
- Osmium is among the least abundant elements in the Earth's continental crust. Recent anthropogenic Os contamination of the environment from mining and smelting activities, automotive catalytic converter use, and hospital discharges has been documented. Here we present evidence for anthropogenic overprinting of the natural Os cycle using a ca. 7000-year record of atmospheric Os deposition and isotopic composition from an ombrotrophic peat bog in NW Spain. Preanthropogenic Os accumulation in this area is 0.10 +/- 0.04 ng m(-2) y(-1). The oldest strata showing human influence correspond to early metal mining and processing on the Iberian Peninsula (ca. 4700-2500 cal. BP). Elevated Os accumulation rates are found thereafter with a local maximum of 1.1 ng m(-2) y(-1) during the Roman occupation of the Iberian Peninsula (ca. 1930 cal. BP)and a further increase starting in 1750 AD with Os accumulation reaching 30 ng m(-2) y(-1) in the most recent samples. Osmium isotopic composition (Os-187/Os-188) indicates that recent elevated Os accumulation results from increased input of unradiogenic Os from industrial and automotive sources as well as from enhanced deposition of radiogenic Os through increased fossil fuel combustion and soil erosion. We posit that the rapid increase in catalyst-equipped vehicles, increased fossil fuel combustion, and changes in land-use make the changes observed in NW Spain globally relevant.
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| 8. |
- Thompson, Rachel, et al.
(author)
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RD-Connect : An Integrated Platform Connecting Databases, Registries, Biobanks and Clinical Bioinformatics for Rare Disease Research
- 2014
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In: Journal of general internal medicine. - : Springer Science and Business Media LLC. - 0884-8734 .- 1525-1497. ; 29:S3, s. S780-S787
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Research review (peer-reviewed)abstract
- Research into rare diseases is typically fragmented by data type and disease. Individual efforts often have poor interoperability and do not systematically connect data across clinical phenotype, genomic data, biomaterial availability, and research/trial data sets. Such data must be linked at both an individual-patient and whole-cohort level to enable researchers to gain a complete view of their disease and patient population of interest. Data access and authorization procedures are required to allow researchers in multiple institutions to securely compare results and gain new insights. Funded by the European Union's Seventh Framework Programme under the International Rare Diseases Research Consortium (IRDiRC), RD-Connect is a global infrastructure project initiated in November 2012 that links genomic data with registries, biobanks, and clinical bioinformatics tools to produce a central research resource for rare diseases.
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| 9. |
- Travaglini, Gabriele, et al.
(author)
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The SAGEX review on scattering amplitudes
- 2022
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In: Journal of Physics A. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 55:44
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Research review (peer-reviewed)abstract
- This is an introduction to, and invitation to read, a series of review articles on scattering amplitudes in gauge theory, gravity, and superstring theory. Our aim is to provide an overview of the field, from basic aspects to a selection of current (2022) research and developments.
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