User-Centered Evaluation of Adaptive and Adaptable Systems

Adaptive and adaptable systems provide tailored output to various users in various contexts. While adaptive systems base their output on implicit inferences, adaptable systems use explicitly provided information. Since the presentation or output of these systems is adapted, standard user-centered evaluation methods do not produce results that can be easily generalized. This calls for a reflection on the appropriateness of standard evaluation methods for user-centered evaluations of these systems. We have conducted a literature review to create an overview of the methods that have been used. When reviewing the empirical evaluation studies we have, among other things, focused on the variables measured and the implementation of results in the (re)design process. The goal of our review has been to compose a framework for user-centered evaluation. In the next phase of the project, we intend to test some of the most valid and feasible methods with an adaptive or adaptable system

The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced gastrointestinal mucositis. Plasma was obtained from pediatric oncology patients at presentation with febrile neutropenia (n = 43) and 24-48 h later (n = 17). The patients were classified as having or not having a bacterial infection. Plasma was also obtained of patients in the absence and in the presence of mucositis (n = 26). At presentation with febrile neutropenia, median IL-8 and PCT levels were significantly increased in patients with a bacterial infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for the early detection of bacterial infection, in combination with clinical parameters or PCT the sensitivity reached 100%. After 24-48 h, only PCT was significantly elevated during bacterial infection. IL-8 levels were significantly increased during mucositis. Mucositis did not cause considerable changes in PCT levels. IL-8 is the most useful marker for the early detection of bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination with clinical parameters or PCT might be even more useful. Gastrointestinal mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and therefore, PCT might be more useful for the detection of bacterial infections during mucositis than IL-8

Discovery of very high energy gamma-ray emission coincident with molecular clouds in the W28 (G6.4-0.1) field

We observed the W28 field (for ~40 h) at Very High Energy (VHE) gamma-ray energies (E>0.1 TeV) with the H.E.S.S. Cherenkov telescopes. A reanalysis of EGRET E>100 MeV data was also undertaken. Results from the NANTEN 4m telescope Galactic plane survey and other CO observations have been used to study molecular clouds. We have discovered VHE gamma-ray emission (HESSJ1801-233) coincident with the northeastern boundary of W28, and a complex of sources (HESSJ1800-240A, B and C) ~0.5 deg south of W28, in the Galactic disc. The VHE differential photon spectra are well fit by pure power laws with indices Gamma~2.3 to 2.7. The NANTEN ^{12}CO(J=1-0) data reveal molecular clouds positionally associating with the VHE emission, spanning a ~15 km s^{-1} range in local standard of rest velocity. The VHE/molecular cloud association could indicate a hadronic origin for HESSJ1801-233 and HESSJ1800-240, and several cloud components in projection may contribute to the VHE emission. The clouds have components covering a broad velocity range encompassing the distance estimates for W28 (~2 kpc), and extending up to ~4 kpc. Assuming a hadronic origin, and distances of 2 and 4 kpc for cloud components, the required cosmic ray density enhancement factors (with respect to the solar value) are in the range ~10 to ~30. If situated at 2 kpc distance, such cosmic ray densities may be supplied by a SNR like W28. Additionally and/or alternatively, particle acceleration may come from several catalogued SNRs and SNR candidates, the energetic ultra compact HII region W28A2, and the HII regions M8 and M20 along with their associated open clusters. Further sub-mm observations would be recommended to probe in detail the dynamics of the molecular clouds at velocites >10 km s^{-1}, and their possible connection to W28.Comment: 10 pages, 4 figures. Accepted for publication in Astronomy & Astrophysics. (Abstract shortened

The role of CTGF in diabetic retinopathy

Connective tissue growth factor (CTGF, CCN2) contributes to fibrotic responses in diabetic retinopathy, both before clinical manifestations occur in the pre-clinical stage of diabetic retinopathy (PCDR) and in proliferative diabetic retinopathy (PDR), the late clinical stage of the disease. CTGF is a secreted protein that modulates the actions of many growth factors and extracellular matrix (ECM) proteins, leading to tissue reorganization, such as ECM formation and remodeling, basal lamina (BL) thickening, pericyte apoptosis, angiogenesis, wound healing and fibrosis. In PCDR, CTGF contributes to thickening of the retinal capillary BL and is involved in loss of pericytes. In this stage, CTGF expression is induced by advanced glycation end products, and by growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β. In PDR, the switch from neovascularization to a fibrotic phase - the angio-fibrotic switch - in PDR is driven by CTGF, in a critical balance with vascular endothelial growth factor (VEGF). We discuss here the roles of CTGF in the pathogenesis of DR in relation to ECM remodeling and wound healing mechanisms, and explore whether CTGF may be a potential novel therapeutic target in the clinical management of early as well as late stages of D

Differential TGF-beta Signaling in Retinal Vascular Cells: A Role in Diabetic Retinopathy?

PURPOSE. An early hallmark of preclinical diabetic retinopathy is thickening of the capillary basal lamina (BL). TGF-beta, a multipotent cytokine acting through its receptors ALK5 and -1, has been postulated to be involved in this phenomenon. In light of this possible role, TGF-beta signaling and its downstream molecular effects were characterized in cultured vascular endothelial cells and pericytes of the retina. METHODS. Bovine retinal endothelial cells and pericytes were stimulated with TGF-beta 1 in the presence or absence of SD-208, a specific inhibitor of the TGF-beta type I receptor ALK5, or ALK5 small interfering (si) RNA. TGF-beta-signaling pathways were characterized by analysis of phosphorylated Smad2 or -1/5/8 proteins and TGF-beta target genes (PAI-1, fibronectin, CTGF, Smad7, and Id1) and protein (fibronectin). RESULTS. ALK5 was expressed in both cell types, whereas ALK1 was exclusively expressed in endothelial cells. In endothelial cells, TGF-beta induced Smad2 phosphorylation at high concentrations, which was efficiently blocked by ALK5 inhibition. In contrast, in pericytes, Smad2 phosphorylation was rapidly induced at low concentrations of TGF-beta. The ALK1-Smad1/5/8 pathway was activated by TGF-beta in endothelial cells only. TGF-beta caused ALK5-mediated upregulation of PAI-1, Smad7, and fibronectin and in pericytes at lower TGF-beta concentrations than in endothelial cells. CTGF mRNA expression was induced only in pericytes. Fibronectin protein was confirmed to be regulated by TGF-beta in both cell types. CONCLUSIONS. TGF-beta signaling in retinal endothelial cells and pericytes show that these cells, and in particular the pericytes, have the essential characteristics to allow for a role of TGF-beta in BL thickening in preclinical diabetic retinopathy. (Invest Ophthalmol Vis Sci. 2010; 51:1857-1865) DOI: 10.1167/iovs.09418

A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy

Introduction In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF and VEGF in the eye is associated with this angiofibrotic switch. This study investigated whether anti-VEGF agents induce accelerated fibrosis in patients with PDR, as predicted by this model. Methods CTGF and VEGF levels were measured by ELISA in 52 vitreous samples of PDR patients, of which 24 patients had received intravitreal bevacizumab 1 week to 3 months before vitrectomy, and were correlated with the degree of vitreoretinal fibrosis as determined clinically and intra-operatively. Results CTGF correlated positively, and VEGF correlated negatively with the degree of fibrosis. The CTGF/VEGF ratio was the strongest predictor of fibrosis. Clinically, increased fibrosis was observed after intravitreal bevacizumab. Conclusions These results confirm that the CTGF/VEGF ratio is a strong predictor of vitreoretinal fibrosis in PDR, and show that intravitreal anti-VEGF treatment causes increased fibrosis in PDR patients. These findings provide strong support for the model that the balance of CTGF and VEGF determines the angiofibrotic switch, and identify CTGF as a possible therapeutic target in the clinical management of PD

Effect of VEGF-A on expression of profibrotic growth factor and extracellular matrix genes in the retina

PURPOSE. Vascular endothelial growth factor-A ( VEGF) causes increased vascular permeability and leukocyte adhesion in preclinical diabetic retinopathy ( PCDR). Another hallmark of PCDR is thickening of the capillary basement membrane ( BM). Recently, VEGF has been shown to induce expression of pro-fibrotic genes such as transforming growth factor ( TGF)-beta 1 and connective tissue growth factor ( CTGF or CCN2) in cultured endothelial cells. Moreover, neutralization of VEGF prevented BM thickening in diabetic mice in vivo. The authors hypothesize that VEGF directly contributes to BM thickening in the diabetic retina by inducing expression of profibrotic growth factors and extracellular matrix (ECM) components. METHODS. Transcription and protein levels of ECM-related genes were evaluated in the rat retina after intravitreal VEGF injection by real-time quantitative PCR, Western blot analysis, and immunohistochemistry. In addition, expression profiles of the same genes in response to VEGF stimulation were investigated in bovine retinal vascular cells in vitro. RESULTS. Intravitreal VEGF injection induced retinal transcription of CYR61 (CCN1), CTGF, TGF-beta 1, tissue inhibitor of metalloproteases ( TIMP)-1 and fibronectin, and protein expression of CYR61, CTGF, TGF-beta 1 and fibronectin. In bovine retinal endothelial cells and pericytes stimulated by VEGF in vitro, gene expression profiles were similar to those in the intact retina in vivo. CONCLUSIONS. VEGF induces profibrotic growth factors and extracellular matrix genes in the retina in vivo, as well as in cultured retinal vascular cells in vitro. The current findings have relevance for understanding the pathogenesis of preclinical DR, where early upregulation of VEGF may cause BM thickening by induction of ECM-related gene