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ABSTRACT IMPACT: We hope to provide a more nuanced understanding of the type-III IFN system, thereby exploring its therapeutic potential in the realm of infectious diseases. OBJECTIVES/GOALS: The role of IFNLR1 receptor dynamics and plasticity in regulating the type-III IFN response is largely unknown. As a specific, powerful component of innate immunity, understanding how the type-III IFN system is regulated could lead to the development of novel therapeutic targets and strategies to face a multitude of viral illnesses. METHODS/STUDY POPULATION: To facilitate our investigation, we will generate doxycycline-inducible FLAG-tagged IFNLR1-expression plasmids representing all known transcriptional variants. These plasmids will allow us to: 1) Evaluate the effect of IFNLR1 surface abundance on the type-III IFN transcriptional profile and 2) Assess the extent of IFNLR1-FLAG co-localization with several notable intracellular structures using immunofluorescence, before and after stimulation with IFNL3. RESULTS/ANTICIPATED RESULTS: We have successfully generated three IFNLR1-FLAG transcriptional variants and confirmed inducible-expression and function in vitro. We are currently assessing the role of surface abundance, internalization, differential isoform expression, and trafficking. DISCUSSION/SIGNIFICANCE OF FINDINGS: By completing this study, we hope to provide a more nuanced understanding of the type-III IFN system, thereby exploring its therapeutic potential in the realm of infectious diseases.
Nutritional therapy is a cornerstone of burns management. The optimal macronutrient intake for wound healing after burn injury has not been identified, although high-energy, high-protein diets are favoured. The present study aimed to identify the optimal macronutrient intake for burn wound healing. The geometric framework (GF) was used to analyse wound healing after a 10 % total body surface area contact burn in mice ad libitum fed one of the eleven high-energy diets, varying in macronutrient composition with protein (P5−60 %), carbohydrate (C20−75 %) and fat (F20−75 %). In the GF study, the optimal ratio for wound healing was identified as a moderate-protein, high-carbohydrate diet with a protein:carbohydrate:fat (P:C:F) ratio of 1:4:2. High carbohydrate intake was associated with lower mortality, improved body weight and a beneficial pattern of body fat reserves. Protein intake was essential to prevent weight loss and mortality, but a protein intake target of about 7 kJ/d (about 15 % of energy intake) was identified, above which no further benefit was gained. High protein intake was associated with delayed wound healing and increased liver and spleen weight. As the GF study demonstrated that an initial very high protein intake prevented mortality, a very high-protein, moderate-carbohydrate diet (P40:C42:F18) was specifically designed. The dynamic diet study was also designed to combine and validate the benefits of an initial very high protein intake for mortality, and subsequent moderate protein, high carbohydrate intake for optimal wound healing. The dynamic feeding experiment showed switching from an initial very high-protein diet to the optimal moderate-protein, high-carbohydrate diet accelerated wound healing whilst preventing mortality and liver enlargement.
When open-cut mines are eventually abandoned, they leave a large hole with sloping sides. The hole fills with rain water, and there is also contaminated run-off from surrounding land, that moves through the rock and eventually through the sloping sides of the abandoned mine. This paper considers a two-dimensional unsteady model motivated by this leaching flow through the rock and into the rain-water reservoir. The stability of the interface between the two fluids is analysed in the inviscid limit. A viscous Boussinesq model is also presented, and a closed-form solution is presented to this problem, after it has been linearized in a manner consistent with Boussinesq theory. That solution suggests that the interfacial zone is effectively neutrally stable as it evolves in time. However, an asymptotic theory in the interfacial region shows the interface to be unstable. In addition, the nonlinear Boussinesq model is solved using a spectral method. Interfacial travelling waves and roll-up are observed and discussed, and compared against the predictions of asymptotic Boussinesq theory.
This study determines the prevalence of inadequate micronutrient intakes consumed by long-term care (LTC) residents. This cross-sectional study was completed in thirty-two LTC homes in four Canadian provinces. Weighed and estimated food and beverage intake were collected over 3 non-consecutive days from 632 randomly selected residents. Nutrient intakes were adjusted for intra-individual variation and compared with the Dietary Reference Intakes. Proportion of participants, stratified by sex and use of modified (MTF) or regular texture foods, with intakes below the Estimated Average Requirement (EAR) or Adequate Intake (AI), were identified. Numbers of participants that met these adequacy values with use of micronutrient supplements was determined. Mean age of males (n 197) was 85·2 (sd 7·6) years and females (n 435) was 87·4 (sd 7·8) years. In all, 33 % consumed MTF; 78·2 % (males) and 76·1 % (females) took at least one micronutrient pill. Participants on a MTF had lower intake for some nutrients (males=4; females=8), but also consumed a few nutrients in larger amounts than regular texture consumers (males=4; females =1). More than 50 % of participants in both sexes and texture groups consumed inadequate amounts of folate, vitamins B6, Ca, Mg and Zn (males only), with >90 % consuming amounts below the EAR/AI for vitamin D, E, K, Mg (males only) and K. Vitamin D supplements resolved inadequate intakes for 50–70 % of participants. High proportions of LTC residents have intakes for nine of twenty nutrients examined below the EAR or AI. Strategies to improve intake specific to these nutrients are needed.
This practical book describes the basic science, clinical presentation and management of the 67 common acute medical presentations stipulated in the Royal College of Physicians syllabus for Core Medical Training and Acute Core Common Stem.Case scenarios are included for each presentation, and guidance about management is offered in the context of national guidelines and important studies Experienced clinicians describe their approach to common difficult problems and explain the answers to questions often asked on the ward round by successive generations of traineesChapters highlight key decisions that need to be made early, common misunderstandings, and risks Detailed discussion provides an understanding of the rationale, allowing the reader to apply their knowledge to other situations Guidance is provided on urgency of referral, safe ambulatory management, and when to seek specialist help.This is an essential resource that provides readers with the knowledge base to practise as a confident medical registrar.
Understanding the nutritional demands on serving military personnel is critical to inform training schedules and dietary provision. Troops deployed to Afghanistan face austere living and working environments. Observations from the military and those reported in the British and US media indicated possible physical degradation of personnel deployed to Afghanistan. Therefore, the present study aimed to investigate the changes in body composition and nutritional status of military personnel deployed to Afghanistan and how these were related to physical fitness. In a cohort of British Royal Marines (n 249) deployed to Afghanistan for 6 months, body size and body composition were estimated from body mass, height, girth and skinfold measurements. Energy intake (EI) was estimated from food diaries and energy expenditure measured using the doubly labelled water method in a representative subgroup. Strength and aerobic fitness were assessed. The mean body mass of volunteers decreased over the first half of the deployment ( − 4·6 (sd 3·7) %), predominately reflecting fat loss. Body mass partially recovered (mean +2·2 (sd 2·9) %) between the mid- and post-deployment periods (P< 0·05). Daily EI (mean 10 590 (sd 3339) kJ) was significantly lower than the estimated daily energy expenditure (mean 15 167 (sd 1883) kJ) measured in a subgroup of volunteers. However, despite the body mass loss, aerobic fitness and strength were well maintained. Nutritional provision for British military personnel in Afghanistan appeared sufficient to maintain physical capability and micronutrient status, but providing appropriate nutrition in harsh operational environments must remain a priority.
Subglacial lakes beneath Antarctica’s fast-moving ice streams are known to undergo ∼1 km3 volume changes on annual timescales. Focusing on the MacAyeal Ice Stream (MacIS) lake system, we create a simple model for the response of subglacial water distribution to lake discharge events through assimilation of lake volume changes estimated from Ice, Cloud and land Elevation Satellite (ICESat) laser altimetry. We construct a steady-state water transport model in which known subglacial lakes are treated as either sinks or sources depending on the ICESat-derived filling or draining rates. The modeled volume change rates of five large subglacial lakes in the downstream portion of MacIS are shown to be consistent with observed filling rates if the dynamics of all upstream lakes are considered. However, the variable filling rate of the northernmost lake suggests the presence of an undetected lake of similar size upstream. Overall, we show that, for this fast-flowing ice stream, most subglacial lakes receive >90% of their water from distant distributed sources throughout the catchment, and we confirm that water is transported from regions of net basal melt to regions of net basal freezing. Our study provides a geophysically based means of validating subglacial water models in Antarctica and is a potential way to parameterize subglacial lake discharge events in large-scale ice-sheet models where adequate data are available.