Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
101
result(s) for
"Swain, Rob"
Sort by:
How are estimated cellular turnover rates influenced by the dynamics of a source population?
Estimating production and loss rates of cell populations is essential but difficult. The current state-of-the-art method to estimate these rates involves mathematical modelling of deuterium labelling experiments. Current models typically assume that the labelling in the precursors of the population of interest (POI) is proportional to the deuterium enrichment in body water/glucose. This assumption is not always true and it is known that this can have a significant effect on the rates estimated from labelling experiments. Here we quantify the effect that different turnover (replacement) rates of the precursors can have on the estimated proliferation and loss rates of a POI by explicitly modelling the dynamics of the precursors. We first confirm earlier results that the labelling curve of the POI only reflects its own turnover rate if either the turnover rate of the precursors is sufficiently fast, or the contribution from the precursors is sufficiently small. Next, we describe three realistic scenarios with a slowly turning over precursor population, and show how this changes the interpretation of the different parameter estimates. Our analyses underpin that uniquely identifying the turnover rate of a POI requires measurements (or knowledge) on the turnover of its immediate precursors.
Journal Article
Replicative history marks transcriptional and functional disparity in the CD8+ T cell memory pool
Clonal expansion is a core aspect of T cell immunity. However, little is known with respect to the relationship between replicative history and the formation of distinct CD8+ memory T cell subgroups. To address this issue, we developed a genetic-tracing approach, termed the DivisionRecorder, that reports the extent of past proliferation of cell pools in vivo. Using this system to genetically ‘record’ the replicative history of different CD8+ T cell populations throughout a pathogen-specific immune response, we demonstrate that the central memory T (TCM) cell pool is marked by a higher number of prior divisions than the effector memory T cell pool, owing to the combination of strong proliferative activity during the acute immune response and selective proliferative activity after pathogen clearance. Furthermore, by combining DivisionRecorder analysis with single-cell transcriptomics and functional experiments, we show that replicative history identifies distinct cell pools within the TCM compartment. Specifically, we demonstrate that lowly divided TCM cells display enriched expression of stem-cell-associated genes, exist in a relatively quiescent state, and are superior in eliciting a proliferative recall response upon activation. These data provide the first evidence that a stem-cell-like memory T cell pool that reconstitutes the CD8+ T cell effector pool upon reinfection is marked by prior quiescence.Schumacher and colleagues have designed a reporter system that allows in vivo tracking of replicative history over many cell generations. Using this system to study acute T cell responses, they uncover substantial diversity in past division of central memory CD8+ T cells and its link to cell state and recall potential.
Journal Article
Revisions to the Canadian Emergency Department Triage and Acuity Scale (CTAS) Guidelines 2016
CAEP Position Statement/Dé Claration de L'ACMU INTRODUCTION The Canadian Triage and Acuity Scale (CTAS) was introduced in 19991after studying the successful National Triage Scale (NTS) from Australia.2The Canadian Association of Emergency Physicians (CAEP), National Emergency Nurses Association (NENA), l'Association des médecins d'urgence du Québec (AMUQ), and the Society of Rural Physicians of Canada (SRPC) formed the CTAS National Working Group to promote its use in Canada. Recognizing that children from neonate to adolescent were not adequately differentiated based on an adult centric triage tool the Canadian Paediatric Society (CPS) approached the CTAS NWG and in collaboration published the Canadian Paediatric Triage and Acuity Scale in 2001.3In 2003 the Canadian Emergency Department Information System (CEDIS) National Working Group published a standardized national ED presenting complaint list which offered an inviting framework for CTAS to build on.4In 2004 adult CTAS was reformulated, using the 17 CEDIS complaint groups and the 165 complaints, primary or 1storder modifiers were defined based on vital signs, pain, and mechanism of injury, to help nurses assign an appropriate triage score.5To further refine the appropriate prioritization, special or 2ndorder modifiers were identified for certain complaints or groups of complaints where the 1storder modifiers were inadequate. In 2008 there was a collective review of and update of the CEDIS complaint list, Adult CTAS and Paediatric CTAS to align them in terms of timing and of structural congruence by adding paediatric definitions and 2ndorder modifiers, and a few paediatric specific CEDIS complaints.6-8As noted previously the structure for CTAS based on...
Journal Article
Effect of cellular aging on memory T-cell homeostasis
The fact that T-cell numbers remain relatively stable throughout life, and that T-cell proliferation rates increase during lymphopenia, has led to the consensus that T-cell numbers are regulated in a density-dependent manner. Competition for resources among memory T cells has been proposed to underlie this ‘homeostatic’ regulation. We first review how two classic models of resource competition affect the T-cell receptor (TCR) diversity of the memory T-cell pool. First, ‘global’ competition for cytokines leads to a skewed repertoire that tends to be dominated by the very first immune response. Second, additional ‘cognate’ competition for specific antigens results in a very diverse and stable memory T-cell pool, allowing every antigen to be remembered, which we therefore define as the ‘gold-standard’. Because there is limited evidence that memory T cells of the same specificity compete more strongly with each other than with memory T cells of different specificities, i.e., for ‘cognate’ competition, we investigate whether cellular aging could account for a similar level of TCR diversity. We define cellular aging as a declining cellular fitness due to reduced proliferation. We find that the gradual erosion of previous T-cell memories due to cellular aging allows for better establishment of novel memories and for a much higher level of TCR diversity compared to global competition. A small continual source (either from stem-cell-like memory T-cells or from naive T-cells due to repeated antigen exposure) improves the diversity of the memory T-cell pool, but remarkably, only in the cellular aging model. We further show that the presence of a source keeps the inflation of chronic memory responses in check by maintaining the immune memories to non-chronic antigens. We conclude that cellular aging along with a small source provides a novel and immunologically realistic mechanism to achieve and maintain the ‘gold-standard’ level of TCR diversity in the memory T-cell pool.
Journal Article
The Sustainability of Evidence-Based Practices in Routine Mental Health Agencies
The research presented here reports on sustainability of the practices within the National Implementing Evidence Based Practices Project for people with serious mental illness. Forty-nine sites completed the initial 2-year implementation phase and were the focus of our study. Our aims were to discern the number of sites that sustained practices 2 years after implementation, the reasons for sustaining or not sustaining, differences in characteristics between the two groups, and the extent and nature of practice adaptations. We used a mixed-methods approach, based on a telephone survey that gathered qualitative and quantitative data from site representatives and others familiar with the sites and practices during the follow-up period. We found that 80% of sites sustained their practices for 2 years post-implementation, that sustainers differed from non-sustainers in several domains: financing, training, fidelity and agency leadership, and that most sites adapted practices moderately to meet state and local needs.
Journal Article
EARLY-AF: Cryoballoon ablation bests antiarrhythmic drugs as first-line intervention
ARRHYTHMIA DISORDERS Cryoballoon ablation was associated with significant improvement over antiarrhythmic drugs as a first-line intervention in preventing atrial fibrillation events, according to the results of the EARLY-AF trial. Secondary endpoints included time to first recurrence of a symptomatic atrial tachyarrhythmia over the same duration and total arrhythmia burden as assessed by the proportion of time in AF as detected by continuous monitoring. [...]assessed were quality of life parameters, ED visit or hospitalization, repeat ablation procedures and adverse events.
Trade Publication Article
Guidance when Applying the Canadian Triage and Acuity Scale (CTAS) to the Geriatric Patient: Executive Summary
(ProQuest: ... denotes formulae and/or non-US-ASCII text omitted; see image) CAEP Position Statement/Dé Claration de L'ACMU INTRODUCTION The first of the baby boomers reached the historic retirement age of 65 in 2011, however, even prior to this emergency department (ED) visits by the elderly were on the rise, correlating with our expanding life span.1The average life expectancy for Canadian males/females born in 1992, 2002, and 2012 respectively is 75/81; 77/82, and 80/84 years as reported by Statistics Canada (http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/health26-eng.htm). Reductions in human mortality leading to extended lifespans reflect improved living standards, education, sanitation, housing, nutrition, public health, and advanced medical care.2It has been proposed that medical advancements contributed 5 of the 30 year increase in life expectancy since 1900, and approximately 3.5 of the 7 year increase since 1950.3From an ED perspective the impact of improved therapies for reversible life threatening conditions such as ST elevation infarcts (STEMIs), cerebrovascular accidents (CVAs) and severe trauma has complemented improved pre hospital care and ED processes to support rapid effective intervention vital to patient survival. Older patient ED visits increased by greater than 30% in the decade between 1993 and 2003, with the number of ED visits over the age of 75 years of age relative to their proportion of the population even higher.4,5This population is also subjected to prolonged ED lengths of stay, and have increased resource utilization and more frequent hospital admissions.6-11 Regarding triage and management challenges among older patients, the literature has identified a number of key differences from the...
Journal Article
Guidance when Applying the Canadian Triage and Acuity Scale (CTAS) to the Geriatric Patient – ERRATUM
Erratum doi:10.1017/cem.2017.363 The original publication of this article had \"Executive Summary\" as part of the article title. Guidance when Applying the Canadian Triage and Acuity Scale (CTAS) to the Geriatric Patient .
Journal Article