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  • Thompson, Robin N., et al. (författare)
  • Key questions for modelling COVID-19 exit strategies
  • 2020
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - 0962-8452 .- 1471-2954. ; 287:1932
  • Tidskriftsartikel (refereegranskat)abstract
    • Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.
  • Trotter, Dinko E. Gonzalez, et al. (författare)
  • In Vivo Imaging of the Programmed Death Ligand 1 by F-18 PET
  • 2017
  • Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:11, s. 1852-1857
  • Tidskriftsartikel (refereegranskat)abstract
    • Programmed death ligand 1 (PD-L1) is an immune regulatory ligand that binds to the T-cell immune check point programmed death 1. Tumor expression of PD-L1 is correlated with immune suppression and poor prognosis. It is also correlated with therapeutic efficacy of programmed death 1 and PD-L1 inhibitors. In vivo imaging may enable real-time follow-up of changing PD-L1 expression and heterogeneity evaluation of PD-L1 expression across tumors in the same subject. We have radiolabeled the PD-L1-binding Affibody molecule NOTA-Z(PD-L1_1) with F-18 and evaluated its in vitro and in vivo binding affinity, targeting, and specificity. Methods: The affinity of the PD-L1-binding Affibody ligand Z(PD-L1_1) was evaluated by surface plasmon resonance. Labeling was accomplished by maleimide coupling of NOTA to a unique cysteine residue and chelation of F-18-AlF. In vivo studies were performed in PD-L1-positive, PD-L1-negative, and mixed tumor-bearing severe combined immunodeficiency mice. Tracer was injected via the tail vein, and dynamic PET scans were acquired for 90 min, followed by gamma-counting biodistribution. Immunohistochemical staining with an antibody specific for anti-PD-L1 (22C3) was used to evaluate the tumor distribution of PD-L1. Immunohistochemistry results were then compared with ex vivo autoradiographic images obtained from adjacent tissue sections. Results: NOTA-Z(PD-L1_1) was labeled, with a radiochemical yield of 15.1% +/- 5.6%, radiochemical purity of 96.7% +/- 2.0%, and specific activity of 14.6 +/- 6.5 GBq/mu mol. Surface plasmon resonance showed a NOTA-conjugated ligand binding affinity of 1 nM. PET imaging demonstrated rapid uptake of tracer in the PD-L1-positive tumor, whereas the PD-L1-negative control tumor showed little tracer retention. Tracer clearance from most organs and blood was quick, with biodistribution showing prominent kidney retention, low liver uptake, and a significant difference between PD-L1-positive (percentage injected dose per gram [%ID/g] = 2.56 +/- 0.33) and -negative (% ID/g = 0.32 +/- 0.05) tumors (P = 0.0006). Ex vivo autoradiography showed excellent spatial correlation with immunohistochemistry in mixed tumors. Conclusion: Our results show that Affibody ligands can be effective at targeting tumor PD-L1 in vivo, with good specificity and rapid clearance. Future studies will explore methods to reduce kidney activity retention and further increase tumor uptake.
  • Weeks, Andrew R., et al. (författare)
  • Assessing the benefits and risks of translocations in changing environments : a genetic perspective
  • 2011
  • Ingår i: Evolutionary Applications. - 1752-4571 .- 1752-4571. ; 4:6, s. 709-725
  • Tidskriftsartikel (refereegranskat)abstract
    • Translocations are being increasingly proposed as a way of conserving biodiversity, particularly in the management of threatened and keystone species, with the aims of maintaining biodiversity and ecosystem function under the combined pressures of habitat fragmentation and climate change. Evolutionary genetic considerations should be an important part of translocation strategies, but there is often confusion about concepts and goals. Here, we provide a classification of translocations based on specific genetic goals for both threatened species and ecological restoration, separating targets based on ‘genetic rescue’ of current population fitness from those focused on maintaining adaptive potential. We then provide a framework for assessing the genetic benefits and risks associated with translocations and provide guidelines for managers focused on conserving biodiversity and evolutionary processes. Case studies are developed to illustrate the framework.
  • Wilhelms, Frank, et al. (författare)
  • The EPICA Dronning Maud Land deep drilling operation
  • 2014
  • Ingår i: Annals of Glaciology. - 0260-3055 .- 1727-5644. ; 55:68, s. 355-366
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the EPICA Dronning Maud Land (East Antarctica) deep drilling operation. Starting with the scientific questions that led to the outline of the EPICA project, we introduce the setting of sister drillings at NorthGRIP and EPICA Dome C within the European ice-coring community. The progress of the drilling operation is described within the context of three parallel, deep-drilling operations, the problems that occurred and the solutions we developed. Modified procedures are described, such as the monitoring of penetration rate via cable weight rather than motor torque, and modifications to the system (e.g. closing the openings at the lower end of the outer barrel to reduce the risk of immersing the drill in highly concentrated chip suspension). Parameters of the drilling (e.g. corebreak force, cutter pitch, chips balance, liquid level, core production rate and piece number) are discussed. We also review the operational mode, particularly in the context of achieved core length and piece length, which have to be optimized for drilling efficiency and core quality respectively. We conclude with recommendations addressing the design of the chip-collection openings and strictly limiting the cable-load drop with respect to the load at the start of the run.
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