The Bank of Canada as Lender of Last Resort

As the ultimate provider of Canadian-dollar liquidity to the financial system, the Bank of Canada has the unique capacity to create Canadian-dollar claims on the central bank and the power to make secured loans or advances to chartered banks and other members of the Canadian Payments Association. The Bank supplies overnight credit on a routine basis through the Standing Liquidity Facility (SLF) to direct participants in the Large Value Transfer System, and Emergency Lending Assistance (ELA) to solvent deposit-taking institutions that require more substantial and prolonged credit. The authors review the policy framework that guides the Bank's lender-of-last-resort function, including the key issues, terms and conditions, and eligibility criteria associated with its SLF and ELA activities. Also discussed are foreign currency ELA, the relationship between SLF and ELA, systemic risk and Bank of Canada intervention, and the potential provision of liquidity to major clearing and settlement systems.

A Boolean Model of the Pseudomonas syringae hrp Regulon Predicts a Tightly Regulated System

The Type III secretion system (TTSS) is a protein secretion machinery used by certain gram-negative bacterial pathogens of plants and animals to deliver effector molecules to the host and is at the core of the ability to cause disease. Extensive molecular and biochemical study has revealed the components and their interactions within this system but reductive approaches do not consider the dynamical properties of the system as a whole. In order to gain a better understanding of these dynamical behaviours and to create a basis for the refinement of the experimentally derived knowledge we created a Boolean model of the regulatory interactions within the hrp regulon of Pseudomonas syringae pathovar tomato strain DC3000 Pseudomonas syringae. We compared simulations of the model with experimental data and found them to be largely in accordance, though the hrpV node shows some differences in state changes to that expected. Our simulations also revealed interesting dynamical properties not previously predicted. The model predicts that the hrp regulon is a biologically stable two-state system, with each of the stable states being strongly attractive, a feature indicative of selection for a tightly regulated and responsive system. The model predicts that the state of the GacS/GacA node confers control, a prediction that is consistent with experimental observations that the protein has a role as master regulator. Simulated gene “knock out” experiments with the model predict that HrpL is a central information processing point within the network

The 2017 Vermont Opioid Prescribing Rules: Prescriber Attitudes

Introduction. In July of 2017, Vermont enacted new rules on acute opioid pre- scribing to reduce misuse, addiction, and overdose associated with prescription opioids. The new rules include requirements of non-opioid therapy use when possible, querying VPMS, patient education and informed consent, and co-prescription of naloxone. Our study objective was to gain insight into the perspectives of opioid prescribers on the new rules. Methods. The 17-item survey included closed and open-ended questions addressing prescriber perceptions about the new rules as well as demographic information about respondents. The survey was sent to Vermont-based opioid prescribers via email, to multiple healthcare organizations and professional societies, and through personal contacts. Open-ended responses were categorized using paired reviewers and group consensus, using a grounded theory approach. Results. A total of 431 responses were obtained, with MD/DOs accounting for 65%, APRNs- 14%, DDS/DMD- 7%, PAs-13%, and NDs- 1%. Of the respondents, 75% thought that more restrictive opioid prescribing rules were necessary, 74% felt the new rules would have some positive effect on the opioid crisis, but only 48% were in favor of the new rules. Barriers to implementation included co-prescribing naloxone (50% were unsuccessful), justifying exceptions to rules in medical record (46% unsuc- cessful), considering non-pharmacologic therapies (39% unsuccessful), and adhering to prescription limits (31% unsuccessful). Conclusions. Roll-out of the new rules has been criticized for implementation issues, overall reducing favorability among prescribers. Feedback obtained may be utilized by the Vermont Health Department and by other states to improve current models of opioid prescribing.https://scholarworks.uvm.edu/comphp_gallery/1264/thumbnail.jp

Rapid fine mapping of causative mutations from sets of unordered, contig-sized fragments of genome sequence

Background Traditional Map based Cloning approaches, used for the identification of desirable alleles, are extremely labour intensive and years can elapse between the mutagenesis and the detection of the polymorphism. High throughput sequencing based Mapping-by-sequencing approach requires an ordered genome assembly and cannot be used with fragmented, un-scaffolded draft genomes, limiting its application to model species and precluding many important organisms. Results We addressed this gap in resource and presented a computational method and software implementations called CHERIPIC (Computing Homozygosity Enriched Regions In genomes to Prioritise Identification of Candidate variants). We have successfully validated implementation of CHERIPIC using three different types of bulk segregant sequence data from Arabidopsis, maize and barley, respectively. Conclusions CHERIPIC allows users to rapidly analyse bulk segregant sequence data and we have made it available as a pre-packaged binary with all dependencies for Linux and MacOS and as Galaxy tool

Mineral Resources: Stocks, Flows, and Prospects

This chapter focuses on metals as they provide the clearest example of the challenges and opportunities that mineral resources present to society, in terms of both primary production and recycling. Basic concepts, information requirements and sources of consumer and industrial resource demand are described as well as the destabilizing effects of volatile resource prices and supply chain disruptions. Challenges facing extraction of in-ground resources and production of secondary resources are discussed and scenarios for the future considered. The results of the scenarios indicate that particularly energy and, as well, water and land requirements could become increasingly constraining factors for metal production. Key research questions are posed and modeling and data priorities discussed, with an emphasis on areas that require novel concepts and analytic tools to help lessen negative environmental impacts associated with minerals. The challenge of sustainability requires collaboration of practitioners and analysts with a multidisciplinary understanding of a broad set of issues, including economics, engineering, geology, ecology, and mathematical modeling, to name a few, as well as policy formulation and implementation.

Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics.

Our knowledge of transcriptional heterogeneities in epithelial stem and progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance and drive wound healing. Previous studies have probed basal cell heterogeneity in stem and progenitor potential, but a comprehensive dissection of basal cell dynamics during differentiation is lacking. Using single-cell RNA sequencing coupled with RNAScope and fluorescence lifetime imaging, we identify three non-proliferative and one proliferative basal cell state in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization. Pseudotemporal trajectory and RNA velocity analyses predict a quasi-linear differentiation hierarchy where basal cells progress from Col17a1Hi/Trp63Hi state to early-response state, proliferate at the juncture of these two states, or become growth arrested before differentiating into spinous cells. Wound healing induces plasticity manifested by dynamic basal-spinous interconversions at multiple basal transcriptional states. Our study provides a systematic view of epidermal cellular dynamics, supporting a revised "hierarchical-lineage" model of homeostasis

Using false discovery rates to benchmark SNP-callers in next-generation sequencing projects

Funding: R.A.F. was funded by the Natural Environment Research Council (NERC). D.A.H. and M.C.F. were supported by the Wellcome Trust. No additional external funding received for this study.Peer reviewedPublisher PD