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.

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.

Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics

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

Lactation and neonatal nutrition: defining and refining the critical questions.

This paper resulted from a conference entitled "Lactation and Milk: Defining and refining the critical questions" held at the University of Colorado School of Medicine from January 18-20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond

Layering in Provenance Systems

Digital provenance describes the ancestry or history of a digital object. Most existing provenance systems, however, operate at only one level of abstraction: the sys- tem call layer, a workflow specification, or the high-level constructs of a particular application. The provenance collectable in each of these layers is different, and all of it can be important. Single-layer systems fail to account for the different levels of abstraction at which users need to reason about their data and processes. These systems cannot integrate data provenance across layers and cannot answer questions that require an integrated view of the provenance. We have designed a provenance collection structure facilitating the integration of provenance across multiple levels of abstraction, including a workflow engine, a web browser, and an initial runtime Python provenance tracking wrapper. We layer these components atop provenance-aware network storage (NFS) that builds upon a Provenance-Aware Storage System (PASS). We discuss the challenges of building systems that integrate provenance across multiple layers of abstraction, present how we augmented systems in each layer to integrate provenance, and present use cases that demonstrate how provenance spanning multiple layers provides functionality not available in existing systems. Our evaluation shows that the overheads imposed by layering provenance systems are reasonable.Engineering and Applied Science

<i>Trypanosoma brucei rhodesiense</i> transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis

Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies. To understand better how infection with this parasite leads to disease, we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys. One infected tsetse fly was allowed to feed on each host individual, and in all cases infections were successful. The characteristics of infection and disease were similar in all hosts, but the rate of progression varied considerably. Parasites were first detected in the blood 4-10 days after infection, showing that migration of parasites from the site of fly bite was very rapid. Anaemia was a key feature of disease, with a reduction in the numbers and average size of red blood cells and associated decline in numbers of platelets and white blood cells. One to six weeks after infection, parasites were observed in the cerebrospinal fluid (CSF), indicating that they had moved from the blood into the brain; this was associated with a white cell infiltration. This study shows that fly-transmitted infection in vervets accurately mimics human disease and provides a robust model to understand better how sleeping sickness develops