A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response. © 2012 Elsevier B.V. All rights reserved.

Development of a medium-capacity guideway transit planning guide

Rapid population increase and booming economic growth have caused a significant escalation in car ownership in many cities, leading to additional or, multiple traffic problems on congested roadways. The increase of automobiles is generating a significant amount of congestion and pollution in many cities. It has become necessary to find a solution to the ever worsening traffic problems in our cities. Building more roadways is nearly impossible due to the limitations of right-of-way in cities. Studies have shown that guideway transit could provide effective transportation and could stimulate land development. The Medium-Capacity Guideway Transit (MCGT) is one of the alternatives to solve this problem. The objective of this research was to better understand the characteristics of MCGT systems, to investigate the existing MCGT systems around the world and determine the main factors behind the planning of successful systems, and to develop a MCGT planning guide. The factors utilized in this study were determined and were analyzed using Excel. A MCGT Planning Guide was developed using Microsoft Visual Basic. ^ A MCGT was defined as a transit system whose capacity can carry up to 20,000 passengers per hour per direction (pphpd). The results shown that Light Rail Transit (LRT) is favored when peak hour demand is less than 13,000 pphpd. Automated People Mover (APM) is favored when the peak hour demand is more than 18,000 pphpd. APM systems could save up to three times the waiting time cost compared to that of the LRT. If comfort and convenience are important, then using an APM does make sense. However, if cost is the critical factor, then LRT will make more sense because it is reasonable service at a reasonable price. If travel time and safety (accident/crush) costs were included in calculating life-cycle “total” costs, the capital cost advantage of LRT disappeared and APM could become very competitive. The results also included a range of cost-performance criteria for MCGT systems that help planners, engineers, and decision-makers to select the most feasible system for their respective areas. ^

The Use of Thermal Capacity in Measuring the Effectiveness of Meals on Wheels Transport Containers

The Meals on Wheels (MOW) program is designed to help combat hunger in persons needing assistance. MOW has a duty not only to provide food but also to ensure that it reaches eligible clients safely. Given the population that MOW serves, transporting food safely takes on increased importance. This experiment focused on the major food safety issue of maintaining temperature integrity through the use of transport containers. For containers that did not contain electric heating elements, several factors influenced how fast the food temperature fell. Those factors included the U-value and size of the container as well as how many meals were in the container. As predicted, the smaller the U-value, the longer it took the temperature to fall. Larger containers did better at maintaining food temperatures, provided they were fully loaded. In general, fully loaded small and medium containers were better at maintaining food temperatures than larger containers loaded with the same number of meals.

Has your work worked you too hard? Physically demanding work and disability in a sample of the older Irish population

There is a heightened need for the practitioner to be alert to the determinants of functional limitations and disabilities owing to the ageing workforce. This study investigated the association between work type and disability in older age in both the paid and the previously unexplored, unpaid worker (household labour).Data on demographic factors, physical measurements, work history and functional status were collected on three hundred and fifty seven 57-80-year-olds. Past or present work was identified as either physically demanding or not. Functional limitations and activities of daily living (ADL) disabilities were assessed using validated scales. Logistic regression was used to examine the relationship between the dependent variables and work type (physically demanding work or not physically demanding work).Over half of the sample reported doing physically demanding work. 20 % had complete function (n = 67), 65 % (n = 223) functional limitations and 15 % (n = 53) ADL disability. Physically demanding work was associated with functional limitations [OR 2.52 (1.41, 4.51), p = 0.01] and ADL disability [OR 2.10 (1.06, 4.17), p = 0.03] after adjustment for a measure of obesity and gender. When gender stratified, looking only at females, physically demanding work was associated with ADL disability [OR 2.79 (1.10, 7.07), p = 0.03] adjusted for a measure of obesity and household labour. Physically demanding work was related to functional limitations and ADL disability in older age. This is valuable information to inform practitioners in the treatment of older people with functional limitations and disabilities and in guiding interventions in the prevention of work related disability.

An exploration of treatment burden and patient capacity in people with stroke

Background and aims: Advances in modern medicine have led to improved outcomes after stroke, yet an increased treatment burden has been placed on patients. Treatment burden is the workload of health care for people with chronic illness and the impact that this has on functioning and well-being. Those with comorbidities are likely to be particularly burdened. Excessive treatment burden can negatively affect outcomes. Individuals are likely to differ in their ability to manage health problems and follow treatments, defined as patient capacity. The aim of this thesis was to explore the experience of treatment burden for people who have had a stroke and the factors that influence patient capacity. Methods: There were four phases of research. 1) A systematic review of the qualitative literature that explored the experience of treatment burden for those with stroke. Data were analysed using framework synthesis, underpinned by Normalisation Process Theory (NPT). 2) A cross-sectional study of 1,424,378 participants >18 years, demographically representative of the Scottish population. Binary logistic regression was used to analyse the relationship between stroke and the presence of comorbidities and prescribed medications. 3) Interviews with twenty-nine individuals with stroke, fifteen analysed by framework analysis underpinned by NPT and fourteen by thematic analysis. The experience of treatment burden was explored in depth along with factors that influence patient capacity. 4) Integration of findings in order to create a conceptual model of treatment burden and patient capacity in stroke. Results: Phase 1) A taxonomy of treatment burden in stroke was created. The following broad areas of treatment burden were identified: making sense of stroke management and planning care; interacting with others including health professionals, family and other stroke patients; enacting management strategies; and reflecting on management. Phase 2) 35,690 people (2.5%) had a diagnosis of stroke and of the 39 co-morbidities examined, 35 were significantly more common in those with stroke. The proportion of those with stroke that had >1 additional morbidities present (94.2%) was almost twice that of controls (48%) (odds ratio (OR) adjusted for age, gender and socioeconomic deprivation; 95% confidence interval: 5.18; 4.95-5.43) and 34.5% had 4-6 comorbidities compared to 7.2% of controls (8.59; 8.17-9.04). In the stroke group, 12.6% of people had a record of >11 repeat prescriptions compared to only 1.5% of the control group (OR adjusted for age, gender, deprivation and morbidity count: 15.84; 14.86-16.88). Phase 3) The taxonomy of treatment burden from Phase 1 was verified and expanded. Additionally, treatment burdens were identified as arising from either: the workload of healthcare; or the endurance of care deficiencies. A taxonomy of patient capacity was created. Six factors were identified that influence patient capacity: personal attributes and skills; physical and cognitive abilities; support network; financial status; life workload, and environment. A conceptual model of treatment burden was created. Healthcare workload and the presence of care deficiencies can influence and be influenced by patient capacity. The quality and configuration of health and social care services influences healthcare workload, care deficiencies and patient capacity. Conclusions: This thesis provides important insights into the considerable treatment burden experienced by people who have had a stroke and the factors that affect their capacity to manage health. Multimorbidity and polypharmacy are common in those with stroke and levels of these are high. Findings have important implications for the design of clinical guidelines and healthcare delivery, for example co-ordination of care should be improved, shared decision-making enhanced, and patients better supported following discharge from hospital.

Normative reference values for the 20-meter shuttlerun test in a population-based sample of schoolchildren in Bogota, Colombia: The FUPRECOL Study

Our aim was to determine the normative reference values of cardiorespiratory fitness (CRF) and to establish the proportion of subjects with low CRF suggestive of future cardio-metabolic risk.

Reducing the global burden of depression : population level analysis of intervention cost-effectiveness in 14 world regions

International evidence on the cost and effects of interventions for reducing the global burden of depression remain scarce. Aims: To estimate the population-level cost-effectiveness of evidence-based depression interventions and their contribution towards reducing current burden. Method: Primary-care-based depression interventions were modelled at the level of whole populations in 14 epidemiological subregions of the world. Total population-level costs (in international dollars or I$) and effectiveness (disability adjusted life years (DALYs) averted) were combined to form average and incremental cost-effectiveness ratios. Results: Evaluated interventions have the potential to reduce the current burden of depression by 10–30%. Pharmacotherapy with older antidepressant drugs, with or without proactive collaborative care, are currently more cost-effective strategies than those using newer antidepressants, particularly in lower-income subregions. Conclusions: Even in resource-poor regions, each DALYaverted by efficient depression treatments in primary care costs less than 1 year of average per capita income, making such interventions a cost-effective use of health resources. However, current levels of burden can only be reduced significantlyif there is a substantialincrease substantial increase intreatment coverage.