CD28 down-regulation on circulating CD4 T-cells is associated with poor prognoses of patients with idiopathic pulmonary fibrosis

Background: Although the etiology of idiopathic pulmonary fibrosis (IPF) remains perplexing, adaptive immune activation is evident among many afflicted patients. Repeated cycles of antigen-induced proliferation cause T-cells to lose surface expression of CD28, and we hypothesized this process might also occur in IPF. Methodology/Principal Findings: Peripheral blood CD4 T-cells from 89 IPF patients were analyzed by flow cytometry and cytokine multiplex assays, and correlated with clinical events. In comparison to autologous CD4 +CD28+cells, the unusual CD4+CD28 null lymphocytes seen in many IPF patients had discordant expressions of activation markers, more frequently produced cytotoxic mediators perforin (2.4±0.8% vs. 60.0±7.4%, p<0.0001) and granzyme B (4.5±2.8% vs.74.9±6.5%, p<0.0001), produced greater amounts of many pro-inflammatory cytokines, and less frequently expressed the regulatory T-cell marker FoxP3 (12.9±1.1% vs. 3.3±0.6% p<0.0001). Infiltration of CD4+CD28null T-cells in IPF lungs was confirmed by confocal microscopy. Interval changes of CD28 expression among subjects who had replicate studies were correlated with conterminous changes of their forced vital capacities (rs = 0.49, p = 0.012). Most importantly, one-year freedom from major adverse clinical events (either death or lung transplantation) was 56±6% among 78 IPF patients with CD4 +CD28+/CD4total≥82%, compared to 9±9% among those with more extensive CD28 down-regulation (CD4+CD28 +/CD4total<82%) (p = 0.0004). The odds ratio for major adverse events among those with the most extensive CD28 down-regulation was 13.0, with 95% confidence intervals 1.6-111.1. Conclusions/Significance: Marked down-regulation of CD28 on circulating CD4 T-cells, a result of repeated antigen-driven proliferations, is associated with poor outcomes in IPF patients. The CD4+CD28null cells of these patients have potentially enhanced pathogenic characteristics, including increased productions of cytotoxic mediators and pro-inflammatory cytokines. These findings show proliferative T-cell responses to antigen(s) resulting in CD28 down-regulation are associated with progression and manifestations of IPF, and suggest assays of circulating CD4 T-cells may identify patients at greatest risk for clinical deterioration. © 2010 Gilani et al

Climate setting in sourcing teams: Developing a measurement scale for team creativity climate

Creative sourcing strategies, designed to extract more value from the supply base, have become a competitive, strategic differentiator. To fuel creativity, companies install sourcing teams that can capitalize on the specialized knowledge and expertise of their employees across the company. This article introduces the concept of a team creativity climate (TCC) - team members' shared perceptions of their joint policies, procedures, and practices with respect to developing creative sourcing strategies – as a means to address the unique challenges associated with a collective, cross-functional approach to develop value-enhancing sourcing strategies. Using a systematic scale development process that validates the proposed concept, the authors confirm its ability to predict sourcing team performance, and suggest some research avenues extending from this concept

Climate change, the Great Barrier Reef and the response of Australians

© 2016, Palgrave Macmillan Ltd. All rights reserved. Inspiration, aspirations, attitudes, and perception of threats play a pivotal role in the way that individuals associate themselves with natural environments. These sentiments affect how people connect to natural places, including their behaviours, perceived responsibility, and the management interventions they support. World Heritage Areas hold an important place in the lives of people who visit, aspire to visit, or derive a sense of security and well-being from their existence. Yet, the connection between people and special places is rarely quantified and policymakers find it difficult to incorporate these human dimensions into decision-making processes. Here we describe the personal concern and connection that Australians have with the Great Barrier Reef and discuss how the results may help with its management. We utilize a statistically representative sample of Australian residents (n = 2,002) and show empirically that climate change is perceived to be the biggest threat to the Great Barrier Reef, and that the Great Barrier Reef inspires Australians, promotes pride, and instills a sense of individual identity and collective responsibility to protect it. An increased understanding of the high levels of personal connection to iconic natural resources may help managers to enhance public support for protecting climate-sensitive systems within Australia and around the world

The Lung Image Database Consortium (LIDC):A comparison of different size metrics for pulmonary nodule measurements

RATIONALE AND OBJECTIVES: To investigate the effects of choosing between different metrics in estimating the size of pulmonary nodules as a factor both of nodule characterization and of performance of computer aided detection systems, since the latters are always qualified with respect to a given size range of nodules. MATERIALS AND METHODS: This study used 265 whole-lung CT scans documented by the Lung Image Database Consortium using their protocol for nodule evaluation. Each inspected lesion was reviewed independently by four experienced radiologists who provided boundary markings for nodules larger than 3 mm. Four size metrics, based on the boundary markings, were considered: a uni-dimensional and two bi-dimensional measures on a single image slice and a volumetric measurement based on all the image slices. The radiologist boundaries were processed and those with four markings were analyzed to characterize the inter-radiologist variation, while those with at least one marking were used to examine the difference between the metrics. RESULTS: The processing of the annotations found 127 nodules marked by all of the four radiologists and an extended set of 518 nodules each having at least one observation with three-dimensional sizes ranging from 2.03 to 29.4 mm (average 7.05 mm, median 5.71 mm). A very high inter-observer variation was observed for all these metrics: 95% of estimated standard deviations were in the following ranges [0.49, 1.25], [0.67, 2.55], [0.78, 2.11], and [0.96, 2.69] for the three-dimensional, the uni-dimensional, and the two bi-dimensional size metrics respectively (in mm). Also a very large difference among the metrics was observed: 0.95 probability-coverage region widths for the volume estimation conditional on uni-dimensional, and the two bi-dimensional size measurements of 10mm were 7.32, 7.72, and 6.29 mm respectively. CONCLUSIONS: The selection of data subsets for performance evaluation is highly impacted by the size metric choice. The LIDC plans to include a single size measure for each nodule in its database. This metric is not intended as a gold standard for nodule size; rather, it is intended to facilitate the selection of unique repeatable size limited nodule subsets