Technical note: Towards more realistic 4DCT(MRI) numerical lung phantoms.

BACKGROUND Numerical 4D phantoms, together with associated ground truth motion, offer a flexible and comprehensive data set for realistic simulations in radiotherapy and radiology in target sites affected by respiratory motion. PURPOSE We present an openly available upgrade to previously reported methods for generating realistic 4DCT lung numerical phantoms, which now incorporate respiratory ribcage motion and improved lung density representation throughout the breathing cycle. METHODS Density information of reference CTs, toget her with motion from multiple breathing cycle 4DMRIs have been combined to generate synthetic 4DCTs (4DCT(MRI)s). Inter-subject correspondence between the CT and MRI anatomy was first established via deformable image registration (DIR) of binary masks of the lungs and ribcage. Ribcage and lung motions were extracted independently from the 4DMRIs using DIR and applied to the corresponding locations in the CT after post-processing to preserve sliding organ motion. In addition, based on the Jacobian determinant of the resulting deformation vector fields, lung densities were scaled on a voxel-wise basis to more accurately represent changes in local lung density. For validating this process, synthetic 4DCTs, referred to as 4DCT(CT)s, were compared to the originating 4DCTs using motion extracted from the latter, and the dosimetric impact of the new features of ribcage motion and density correction were analyzed using pencil beam scanned proton 4D dose calculations. RESULTS Lung density scaling led to a reduction of maximum mean lung Hounsfield units (HU) differences from 45 to 12 HU when comparing simulated 4DCT(CT)s to their originating 4DCTs. Comparing 4D dose distributions calculated on the enhanced 4DCT(CT)s to those on the original 4DCTs yielded 2%/2 mm gamma pass rates above 97% with an average improvement of 1.4% compared to previously reported phantoms. CONCLUSIONS A previously reported 4DCT(MRI) workflow has been successfully improved and the resulting numerical phantoms exhibit more accurate lung density representations and realistic ribcage motion

Knowledge and Implementation of Climate Change Adaptation in the Infrastructure Sector in Nunavut, Canada

The Arctic is at the forefront of climate change and is considered to be the most at risk, warming at twice the rate of the global annual average. The environment and its inhabitants are and will be subjected to deep transformational shifts, with changes in temperature and climate having potentially worldwide repercussions. Global attention for the Arctic region has further risen by the increasing natural resource opportunities and changes in its accessibility, emergence of new transportation routes and geopolitical shifts. In the context of the Canadian Arctic, debates over appropriate policy action on climate change adaptation is a prominent topic for policy at all levels of government and across all sectors. While mitigation is certainly needed both in Canada and internationally, in the context of the territory of Nunavut, preparedness and adaptation are perhaps the most important and immediate need. Assessing climate change adaptation considerations in the infrastructure sector in particular is crucial as both society and individuals are dependent on it. Infrastructure in Nunavut is built to withstand harsh seasonal conditions and is reliant on shipments of resources and material for maintenance and construction. Most of this infrastructure is susceptible to climate variability and thus vulnerable to climate change. The purpose of this thesis project is to identify and understand in what ways existing knowledge plays a role in the infrastructure sector and how this is implemented and operationalized for infrastructure development and policy in the context of Nunavut. The research hopes to contribute to the knowledge of climate change adaptation in infrastructure in vulnerable environments and foster greater dialogue on the topic, as well as encourage proactive action for climate-sensitive infrastructure development in Nunavut.The Arctic is experiencing dramatic climate change and has been identified to be undergoing the most pronounced projected warming. With potential global repercussions, there has been an urgent need to understand how climate change affects the Arctic region. The Arctic environment and its inhabitants are and will be subjected to deep transformational shifts, with changes in temperature and climate having potentially worldwide repercussions. In the context of the Canadian Arctic, debates over appropriate policy action on climate change adaptation is a prominent topic for policy at all levels of government and across all sectors. In the context of the territory of Nunavut, preparedness and adaptation are perhaps the most important and immediate need. Assessing climate change adaptation considerations in the infrastructure sector in particular is crucial as both society and individuals. Infrastructure in Nunavut is built to withstand harsh seasonal conditions but is still susceptible to climate variability. The purpose of this thesis project is to identify and understand in what ways existing knowledge plays a role in the infrastructure sector and how this is implemented and operationalized for infrastructure development and policy in the context of Nunavut. Building and maintaining infrastructure that can withstand climate impacts and variability and, developing the capacity and policy prioritization of CCA for the infrastructure sector requires continued efforts from across different sectors and scales. General data scarcity coupled with research disparities between communities in the region remain a major obstacle and pose a risk towards blanket policies. ‘Connecting the dots’ between both the CCA research realm and the infrastructure research realm has been highlighted as a crucial point throughout this research. The research also found limited number of case studies in Nunavut where concrete action in line with planned and prepared adaptation took place. There seems to be a disconnect between the governance levels as many actions are often ad-hoc and lack the long-term commitments that mainstreaming, and integration of adaptation action and decision-making require. The results show that although adaptation has been taking place, a need for continued dialogue between federal, territorial and community-level stakeholders is key to develop a long-term resilient A qualitative case study approach was chosen in order to understand the processes and in what way CCA knowledge and ongoing measures are implemented and integrated in critical infrastructure projects and policies in the context of Nunavut, utilizing (1) a scoping review and a review of grey literature and publications, in combination with (2) semi-structured interviews with experts and researchers in the field. An assessment of the current situation and potential impacts of CCA measures for infrastructure can contribute to synergies between adaptation strategies and other infrastructure policy arenas. The research hopes to contribute to the knowledge of CCA in infrastructure in vulnerable environments and foster greater dialogue on the topic, as well as encourage proactive action for climate-sensitive infrastructure development in Nunavut

Collaborative Design of Pathways to Sustainability. Guidebook for designing and running in-person workshops

The guidebook is meant as a practical introduction and step-by-step instruction on how to design and apply the Collaborative Systems Mapping of Sustainable Pathways (CoSMoS) method. The process has been developed to bridge the gap between science, policy, and society. Scientific knowledge about sustainability challenges was used to develop multiple global scenarios. However, stakeholder engagement in scenario planning is often misunderstood as a way to give expert input to scientists and provide feedback on research results. If scenario efforts are to be useful for policy development, they need to clearly indicate the sphere of control where stakeholders representing specific decision unit(s) can develop robust strategies. The CoSMoS process allows them to develop strategic insights by building on selected representations of real-world structures and processes. The guidebook provides a necessary basis to understand the process so that readers can use it, adapt it to specific circumstances, and successfully execute it. The guide is an updated version of the ISWEL guidebook on Policy Simulations and is designed as a manual for organisations interested in using Collaborative Systems Mapping of Sustainable Pathways for face-to-face workshops. This includes organisations directly or indirectly involved in the process of policy development, especially in the context of various crises, such as climate emergency, biodiversity loss, rise in populism, and many others. The methodology strongly emphasises the positive, active, and inclusive approaches to co-creating sustainability pathways to desired futures. The guidebook will: 1. explain the assumptions underlying the co-creation of scenarios and pathways, 2. compare and contrast them with other, similar tools, and 3. instruct how to adapt, design, and run new CoSMoS workshop sessions

Increased Expression of Chemerin in Squamous Esophageal Cancer Myofibroblasts and Role in Recruitment of Mesenchymal Stromal Cells

Stromal cells such as myofibroblasts influence tumor progression. The mechanisms 45 are unclear but may involve effects on both tumor cells and recruitment of bone 46 marrow-derived mesenchymal stromal cells (MSCs) which then colonize tumors. 47 Using iTRAQ and LC-MS/MS we identified the adipokine, chemerin, as 48 overexpressed in esophageal squamous cancer associated myofibroblasts (CAMs) 49 compared with adjacent tissue myofibroblasts (ATMs). The chemerin receptor, 50 ChemR23, is expressed by MSCs. Conditioned media (CM) from CAMs significantly 51 increased MSC cell migration compared to ATM-CM; the action of CAM-CM was 52 significantly reduced by chemerin-neutralising antibody, pretreatment of CAMs with 53 chemerin siRNA, pretreatment of MSCs with ChemR23 siRNA, and by a ChemR23 54 receptor antagonist, CCX832. Stimulation of MSCs by chemerin increased 55 phosphorylation of p42/44, p38 and JNK-II kinases and inhibitors of these kinases 56 and PKC reversed chemerin-stimulated MSC migration. Chemerin stimulation of 57 MSCs also induced expression and secretion of macrophage inhibitory factor (MIF) 58 that tended to restrict migratory responses to low concentrations of chemerin but not 59 higher concentrations. In a xenograft model consisting of OE21 esophageal cancer 60 cells and CAMs, homing of MSCs administered i.v. was inhibited by CCX832. Thus, 61 chemerin secreted from esophageal cancer myofibroblasts is a potential 62 chemoattractant for MSCs and its inhibition may delay tumor progression