A combination of local inflammation and central memory T cells potentiates immunotherapy in the skin

Adoptive T cell therapy uses the specificity of the adaptive immune system to target cancer and virally infected cells. Yet the mechanism and means by which to enhance T cell function are incompletely described, especially in the skin. In this study, we use a murine model of immunotherapy to optimize cell-mediated immunity in the skin. We show that in vitro - derived central but not effector memory-like T cells bring about rapid regression of skin-expressing cognate Ag as a transgene in keratinocytes. Local inflammation induced by the TLR7 receptor agonist imiquimod subtly yet reproducibly decreases time to skin graft rejection elicited by central but not effector memory T cells in an immunodeficient mouse model. Local CCL4, a chemokine liberated by TLR7 agonism, similarly enhances central memory T cell function. In this model, IL-2 facilitates the development in vivo of effector function from central memory but not effector memory T cells. In a model of T cell tolerogenesis, we further show that adoptively transferred central but not effector memory T cells can give rise to successful cutaneous immunity, which is dependent on a local inflammatory cue in the target tissue at the time of adoptive T cell transfer. Thus, adoptive T cell therapy efficacy can be enhanced if CD8+ T cells with a central memory T cell phenotype are transferred, and IL-2 is present with contemporaneous local inflammation. Copyright © 2012 by The American Association of Immunologists, Inc.

Experimental investigation on lateral impact response of concrete-filled double-skin tube columns using horizontal-impact-testing system

This paper presents an experimental investigation on the lateral impact performance of axially loaded concrete-filled double-skin tube (CFDST) columns. These columns have desirable structural and constructional properties and have been used as columns in building, legs of off shore platforms and as bridge piers. Since they could be vulnerable to impact from passing vessels or vehicles, it is necessary to understand their behaviour under lateral impact loads. With this in mind, an experimental method employing an innovative instrumented horizontal impact testing system (HITS) was developed to apply lateral impact loads whilst the column maintained a static axial pre-loading to examine the failure mechanism and key response parameters of the column. These included the time histories of impact force, reaction forces, global lateral deflection and permanent local buckling profile. Eight full scale columns were tested for key parameters including the axial load level and impact location. Based on the test data, the failure mode, peak impact force, impact duration, peak reaction forces, reaction force duration, column maximum and residual global deflections and column local buckling length, depth and width under varying conditions are analysed and discussed. It is evident that the innovative HITS can successfully test structural columns under the combination of axial pre-loading and impact loading. The findings on the lateral impact response of the CFDST columns can serve as a benchmark reference for their future analysis and design.

The skin safety model: Reconceptualizing skin vulnerability in older patients

Purpose: To develop a unique skin safety model (SSM) that offers a new and unified perspective on the diverse yet interconnected antecedents that contribute to a spectrum of potential iatrogenic skin injuries in older hospitalized adults. Organizing Construct: Discussion paper. Methods: A literature search of electronic databases was conducted for published articles written in English addressing skin integrity and iatrogenic skin injury in elderly hospital patients between 1960 and 2014. Findings: There is a multiplicity of literature outlining the etiology, prevention, and management of specific iatrogenic skin injuries. Complex and interrelated factors contribute to iatrogenic skin injury in the older adult, including multiple comorbidities, factors influencing healthcare delivery, and acute situational stressors. A range of injuries can result when these factors are com- plicated by skin irritants, pressure, shear, or friction; however, despite skin injuries sharing multiple ntecedents, no unified overarching skin safety conceptual model has been published. Conclusions: The SSM presented in this article offers a new, unified framework that encompasses the spectrum of antecedents to skin vulnerability as well as the spectrum of iatrogenic skin injuries that may be sustained by older acute care patients. Current skin integrity frameworks address prevention and management of specific skin injuries. In contrast, the SSM recognizes the complex interplay of patient and system factors that may result in a range of iatrogenic skin injuries. Skin safety is reconceptualized into a single model that has the potential for application at the individual patient level, as well as health-care systems and governance levels. Clinical Relevance: Skin safety is concerned with keeping skin safe from any iatrogenic skin injury, and remains an ongoing challenge for healthcare providers. A conceptual framework that encompasses all of the factors that may contribute to a range of iatrogenic skin injuries is essential, and guides the clinician in maintaining skin integrity in the vulnerable older patient.

Concrete-filled double skin tube columns subjected to lateral impact loading: Experimental and numerical study

This research treats the lateral impact behaviour of composite columns, which find increasing use as bridge piers and building columns. It offers (1) innovative experimental methods for testing structural columns, (2) dynamic computer simulation techniques as a viable tool in analysis and design of such columns and (3) significant new information on their performance which can be used in design. The research outcomes will enable to protect lives and properties against the risk of vehicular impacts caused either accidentally or intentionally.

Experimental study on behaviour of concrete filled double skin tube columns under lateral impact loading

This paper presents an experimental investigation on the lateral impact response of axially loaded concrete filled double skin tube (CFDST) columns. A total of four test series are being conducted at Queensland University of Technology using a novel horizontal impact-testing rig. The test results reported in this paper are from the first test series, where the columns are pinned at both ends and impacted at mid-span. In the next three series, effects of support conditions, impact location and repeated impact will be treated. The main objectives of the current paper are to describe the innovative testing procedure and provide some insight into the lateral impact behavior and failure of simply supported axially pre-loaded CFDST columns. The results include time histories of impact forces, reaction forces, axial force and global lateral deflection. Based on the test data, the failure mode, peak impact force, peak reaction forces, maximum deflection and residual deflection, with and without axial load, are analyzed and discussed. The findings of this study will serve as a benchmark reference for future analysis and design of CFDST columns.