Detection of curved lines with B-COSFIRE filters: A case study on crack delineation

The detection of curvilinear structures is an important step for various computer vision applications, ranging from medical image analysis for segmentation of blood vessels, to remote sensing for the identification of roads and rivers, and to biometrics and robotics, among others. %The visual system of the brain has remarkable abilities to detect curvilinear structures in noisy images. This is a nontrivial task especially for the detection of thin or incomplete curvilinear structures surrounded with noise. We propose a general purpose curvilinear structure detector that uses the brain-inspired trainable B-COSFIRE filters. It consists of four main steps, namely nonlinear filtering with B-COSFIRE, thinning with non-maximum suppression, hysteresis thresholding and morphological closing. We demonstrate its effectiveness on a data set of noisy images with cracked pavements, where we achieve state-of-the-art results (F-measure=0.865). The proposed method can be employed in any computer vision methodology that requires the delineation of curvilinear and elongated structures.Comment: Accepted at Computer Analysis of Images and Patterns (CAIP) 201

Indigenous markets for dairy products in Africa: trade-offs between food safety and economics

In the absence of information on which to base policies in emerging dairy markets in developing countries, public officials have tended to rely on models for dairy product marketing and health assurance derived from industrialised countries where large-scale production systems, cold-chain pathways and milk pasteurization and packaging are key features. These models have invariably failed in many African market situations where small-scale dairy systems without cold-chain market pathways currently dominate and will continue to do so in the foreseeable future. The main reason is simple: many resource-poor consumers simply refuse to pay the extra costs that pasteurized, packaged milk incurs, and prefer to buy raw milk and boil it themselves. But the role of traditional preferences should not be discounted: in Kenya, high-income consumers express the same preference for raw milk as do those with lower income, and often end up buying more of it. As a result, informal or raw milk and traditional product markets generally dominate in developing countries, comprising over 90% of the market in Tanzania and Uganda, for example, and some 83% of the market of the world’s largest milk producer, India. In Kenya, the informal market has some 85% market share. The issue, of course, is public health concerns linked to raw milk. Current dairy market policies throughout the developing world have largely been adopted from the West, and reflect international standards of food safety, etc. However, as the percentages above show, they are being systematically ignored, and as a result, most consumers buy milk and dairy products that are completely outside any regulatory environment. It is possible that to better address the public health issues, policies may need to take a more pro-active approach to informal milk trading, and which better address the realities of consumer willingness to pay for higher standards. The policy question which needs to be answered is thus: is it preferable to maintain strict milk standards which result in higher costs and thereby free most marketed milk into informal channels, or is the public better off by standards that are relaxed but capture more of the informal market? If standards were relaxed to allow raw milk marketing, yet maintain some regulations regarding handling and if some incentives were given to milk traders to comply (e.g., training and certification), then a much larger proportion of the milk market may fall under regulatory control, improving the average standards of milk in the market. An important step to addressing this issue is to collect quantitative and qualitative information about milk-borne health risks under different production and marketing situations. This paper describes specific dairy marketing studies in Kenya, Ghana and Tanzania aimed at assessing public health risks from informally marketed milk and examines the economic trade-offs that policy makers should consider. Preliminary results from Kenya are presented and recommendations on cost-effective and practical interventions to improve milk safety made

Specific Disease Knowledge as Predictor of Susceptibility to Availability Bias in Diagnostic Reasoning:a Randomized Controlled Experiment

BACKGROUND: Bias in reasoning rather than knowledge gaps has been identified as the origin of most diagnostic errors. However, the role of knowledge in counteracting bias is unclear. OBJECTIVE: To examine whether knowledge of discriminating features (findings that discriminate between look-alike diseases) predicts susceptibility to bias. DESIGN: Three-phase randomized experiment. Phase 1 (bias-inducing): Participants were exposed to a set of clinical cases (either hepatitis-IBD or AMI-encephalopathy). Phase 2 (diagnosis): All participants diagnosed the same cases; 4 resembled hepatitis-IBD, 4 AMI-encephalopathy (but all with different diagnoses). Availability bias was expected in the 4 cases similar to those encountered in phase 1. Phase 3 (knowledge evaluation): For each disease, participants decided (max. 2 s) which of 24 findings was associated with the disease. Accuracy of decisions on discriminating features, taken as a measure of knowledge, was expected to predict susceptibility to bias. PARTICIPANTS: Internal medicine residents at Erasmus MC, Netherlands. MAIN MEASURES: The frequency with which higher-knowledge and lower-knowledge physicians gave biased diagnoses based on phase 1 exposure (range 0-4). Time to diagnose was also measured. KEY RESULTS: Sixty-two physicians participated. Higher-knowledge physicians yielded to availability bias less often than lower-knowledge physicians (0.35 vs 0.97; p = 0.001; difference, 0.62 [95% CI, 0.28-0.95]). Whereas lower-knowledge physicians tended to make more of these errors on subjected-to-bias than on not-subjected-to-bias cases (p = 0.06; difference, 0.35 [CI, - 0.02-0.73]), higher-knowledge physicians resisted the bias (p = 0.28). Both groups spent more time to diagnose subjected-to-bias than not-subjected-to-bias cases (p = 0.04), without differences between groups. CONCLUSIONS: Knowledge of features that discriminate between look-alike diseases reduced susceptibility to bias in a simulated setting. Reflecting further may be required to overcome bias, but succeeding depends on having the appropriate knowledge. Future research should examine whether the findings apply to real practice and to more experienced physicians

The effects of treatment with chemotherapy on energy metabolism and inflammatory mediators in small-cell lung carcinoma.

A disturbed energy balance has been demonstrated in lung cancer patients. Both an enhanced resting energy expenditure (REE) and a decreased energy intake contribute to weight loss. Enhanced systemic levels of inflammatory mediators were found to be related to the enhanced REE in lung cancer. The aim of the present study was to investigate energy metabolism and systemic levels of inflammatory mediators in small-cell lung carcinoma (SCLC) patients before and after treatment with chemotherapy. Hypermetabolism and an enhanced inflammatory response have already been demonstrated in SCLC by our group before. Twelve newly diagnosed SCLC patients were consecutively included in the study. REE was measured by indirect calorimetry and body composition was determined by bioelectrical impedance (BIA) before and 1 month after treatment. To assess the inflammatory state the acute-phase proteins, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP), both soluble tumour necrosis factor (TNF) receptors, (sTNF-R)-55 and sTNF-R75, and soluble intercellular adhesion molecule (sICAM)-1 were measured in plasma before and 1 month after treatment. CRP was assessed by turbidemetry, whereas the other inflammatory parameters were measured by enzyme-linked immunosorbent assay (ELISA). A significant reduction in REE was found irrespective of therapeutic outcome, whereas body weight and body composition remained stable. The acute-phase proteins CRP and LBP were reduced significantly after treatment with chemotherapy, whereas both sTNF receptors and sICAM-1 remained enhanced. No correlation, however, existed between the decrease in REE and the decrease in the acute-phase proteins. In conclusion, chemotherapeutic treatment attenuates the tumour-related metabolic derangements and acute-phase response

Stabilisation of β-Catenin Downstream of T Cell Receptor Signalling

The role of TCF/β-catenin signalling in T cell development is well established, but important roles in mature T cells have only recently come to light.Here we have investigated the signalling pathways that are involved in the regulation of β-catenin in primary human T cells. We demonstrate that β-catenin expression is upregulated rapidly after T cell receptor (TCR) stimulation and that this involves protein stabilisation rather than an increase in mRNA levels. Similar to events in Wnt signalling, the increase in β-catenin coincides with an inhibition of GSK3, the kinase that is required for β-catenin degradation. β-catenin stabilisation in T cells can also be induced by the activation of PKC with phorbol esters and is blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K) and phospholipase C (PKC). Upon TCR signalling, β-catenin accumulates in the nucleus and, parallel to this, the ratio of TCF1 isoforms is shifted in favour of the longer β-catenin binding isoforms. However, phosphorylated β-catenin, which is believed to be inactive, can also be detected and the expression of Wnt target genes Axin2 and dickkopf is down regulated.These data show that in mature human T cells, TCR signalling via PI3K and PKC can result in the stabilisation of β-catenin, allowing β-catenin to migrate to the nucleus. They further highlight important differences between β-catenin activities in TCR and Wnt signalling

Natural history of Arabidopsis thaliana and oomycete symbioses

Molecular ecology of plant–microbe interactions has immediate significance for filling a gap in knowledge between the laboratory discipline of molecular biology and the largely theoretical discipline of evolutionary ecology. Somewhere in between lies conservation biology, aimed at protection of habitats and the diversity of species housed within them. A seemingly insignificant wildflower called Arabidopsis thaliana has an important contribution to make in this endeavour. It has already transformed botanical research with deepening understanding of molecular processes within the species and across the Plant Kingdom; and has begun to revolutionize plant breeding by providing an invaluable catalogue of gene sequences that can be used to design the most precise molecular markers attainable for marker-assisted selection of valued traits. This review describes how A. thaliana and two of its natural biotrophic parasites could be seminal as a model for exploring the biogeography and molecular ecology of plant–microbe interactions, and specifically, for testing hypotheses proposed from the geographic mosaic theory of co-evolution

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

A novel germline mutation of PTEN associated with brain tumours of multiple lineages

We have identified a novel germline mutation in the PTEN tumour suppressor gene. The mutation was identified in a patient with a glioma, and turned out to be a heterozygous germline mutation of PTEN (Arg234Gln), without loss of heterozygosity in tumour DNA. The biological consequences of this germline mutation were investigated by means of transfection studies of the mutant PTEN molecule compared to wild-type PTEN. In contrast to the wild-type molecule, the mutant PTEN protein is not capable of inducing apoptosis, induces increased cell proliferation and leads to high constitutive PKB/Akt activation, which cannot be increased anymore by stimulation with insulin. The reported patient, in addition to glioma, had suffered from benign meningioma in the past but did not show any clinical signs of Cowden disease or other hereditary diseases typically associated with PTEN germline mutations. The functional consequences of the mutation in transfection studies are consistent with high proliferative activity. Together, these findings suggest that the Arg234Gln missense mutation in PTEN has oncogenic properties and predisposes to brain tumours of multiple lineages